available evidence of antibiotic resistance from extended ... · extended-spectrum β-lactamases...

Bull World Health Organ 201997486ndash501B | doi httpdxdoiorg102471BLT18225698

Systematic reviews

486

IntroductionAntimicrobial resistance occurs when bacteria are no longer susceptible to the drugs used for treatment1 Increasingly there are fewer antimicrobial drugs available to effectively treat common as well as life-threatening infections Annual deaths from untreatable infections may rise from estimated 700 000 in 2015 to 10 million by 2050 if antimicrobial resistance is not controlled2 Common procedures such as surgery or cancer chemotherapy may become too dangerous to perform without effective antibiotics

Extended-spectrum β-lactamases are enzymes that cause resistance to some of the most commonly used antibiotics3 including all penicillins cephalosporins and monobactams3 Fortunately these enzymes have yet to confer resistance to carbapenems making these drugs valuable for serious extended-spectrum β-lactamase-producing bacterial infec-tions4 However there have been recent outbreaks of extend-ed-spectrum β-lactamase-producing Klebsiella spp with carbapenem resistance resulting in extremely high rates of mortality56 Within the already limited selection of antibiotics available to treat these infections fewer are approved for use in children7 Children are particularly vulnerable to bacterial infections compared with young adults due to their immature immune systems89

The World Health Organization (WHO) South-East Asia and Western Pacific Regions have over 43 billion of the worldrsquos

population of 77 billion including two of the most populous countries with heavy consumption of antibiotics China and India10 Research suggests these regions have high antimi-crobial resistance rates to extended-spectrum β-lactamase-producing bacteria in the paediatric population11 Poor-quality antibiotics and unsupervised use are common across the Regions The available studies provide an overall impression of the prevalence of antibiotic resistance in the Regions but better evidence is needed about the risk factors and outcomes for children with these infections We therefore aimed to make a systematic review and meta-analysis of the risk factors and outcomes of infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in children and young adults in the South-East Asia and the Western Pacific We also mapped the prevalence of extended-spectrum β-lactamase-associated infections in countries and areas of the Regions using the available surveillance data

MethodsMeta-analysis

We conducted the meta-analysis in accordance with the Co-chrane handbook for systematic reviews of interventions12 All procedures followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines13 The study was reg-istered in the PROSPERO International prospective register of systematic reviews (CRD42017069701)

a School of Public Health Patrick Manson Building (North Wing) 7 Sassoon Road Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong Special Administrative Region China

Correspondence to Yanhong Jessika Hu (email huhubestgmailcom)(Submitted 20 October 2018 ndash Revised version received 8 April 2019 ndash Accepted 9 April 2019 ndash Published online 14 May 2019 )

Available evidence of antibiotic resistance from extended-spectrum β-lactamase-producing Enterobacteriaceae in paediatric patients in 20 countries a systematic review and meta-analysisYanhong Jessika Hua Anju Ogyua Benjamin J Cowlinga Keiji Fukudaa amp Herbert H Panga

Objective To make a systematic review of risk factors outcomes and prevalence of extended-spectrum β-lactamase-associated infection in children and young adults in South-East Asia and the Western PacificMethods Up to June 2018 we searched online databases for published studies of infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in individuals aged 0ndash21 years We included casendashcontrol cohort cross-sectional and observational studies reporting patients positive and negative for these organisms For the meta-analysis we used random-effects modelling of risk factors and outcomes for infection and meta-regression for analysis of subgroups We mapped the prevalence of these infections in 20 countries and areas using available surveillance dataFindings Of 6665 articles scanned we included 40 studies from 11 countries and areas in the meta-analysis The pooled studies included 2411 samples testing positive and 2874 negative A higher risk of infection with extended-spectrum β-lactamase-producing bacteria was associated with previous hospital care notably intensive care unit stays (pooled odds ratio OR 65 95 confidence interval CI 304 to 1373) antibiotic exposure (OR 48 95 CI 225 to 1027) and certain co-existing conditions Empirical antibiotic therapy was protective against infection (OR 029 95 CI 011 to 079) Infected patients had longer hospital stays (26 days 95 CI 1281 to 3889) and higher risk of death (OR 32 95 CI 182 to 580) The population prevalence of infection was high in these regions and surveillance data for children were scarceConclusion Antibiotic stewardship policies to prevent infection and encourage appropriate treatment are needed in South-East Asia and the Western Pacific

Systematic reviews

487Bull World Health Organ 201997486ndash501B| doi httpdxdoiorg102471BLT18225698

Systematic reviewsAntibiotic resistance in Asia Pacific childrenYanhong Jessika Hu et al

Search strategy

We made a comprehensive search without language limitation of online databases for articles published from 1 January 1940 to 30 June 2018 (Box 1) Two researchers independently con-ducted the search and screened the titles abstracts and full texts of the pa-pers We used a standardized piloted data collection form to determine whether papers were appropriate for inclusion The researchers applied the NewcastlendashOttawa scale to assess risk of bias in non-randomized stud-ies14 Studies scoring ge 5 and le 8 were designated low risk of bias ge 3 and le 4 as moderate and le 2 as high We incorporated the quality assessment results into our sensitivity analysis using the Meta-analyses Of Observa-tional Studies in Epidemiology check-list Discrepancies at any stage of the analysis were resolved by consensus of the researchers

Selection criteria

We included cohort casendashcontrol and observational or cross-sectional stud-ies We defined the target population as children aged from birth to 21 years according the American Academy of Paediatrics guidelines15 We included studies that were conducted in the WHO South-East Asia and Western Pacific Regions and that recorded both positive and negative results of testing for extended-spectrum β-lactamase-producing bacteria

Outcome measures

The principal outcome measure was patientsrsquo infection status defined by whether specimens obtained test-ed positive or negative for infection with extended-spectrum β-lactamase-producing bacteria We analysed infec-tion status by risk sub-groups medical history in the 3 months before the infection (hospital stay intensive care unit admission surgery) exposure to invasive life support antibiotic therapy and co-morbidities or underlying conditions Other outcomes recorded were hospital length of stay mortal-ity persistent bacteraemia antibiotic residence and duration of fever after antibiotic therapy

Data synthesis and analysis

For the meta-analysis we pooled the data on number of isolates (four studies) or patients with isolates (37 studies) us-ing a MantelndashHaenszel random-effects model to determine the risk of infection with extended-spectrum β-lactamase-producing bacteria16 We calculated pooled odds ratio (OR) and 95 con-fidence intervals (CI) for dichotomous outcomes and weighted mean difference and 95 CI for continuous outcomes All tests were two-tailed and P lt 005 was considered statistically significant If studies provided median and inter-quartile range we made estimates of the mean and standardized deviation (SD)17

We assessed the heterogeneity of the studies using the I2 statistic which eval-

uates the consistency of study results The cut-off for defining heterogeneity was I2 gt 5018 Our sensitivity analyses were based on sample size on the over-all summary estimates19 We evaluated whether this restricted analysis affected the magnitude direction and statistical significance of the overall summary estimate Additional sensitivity analy-ses assessed the different types of study designs settings and risk of bias

We carried out meta-regression to explore each potential factor contribut-ing to heterogeneity between studies such as study location design duration and setting and patientsrsquo age and diag-nosis for all included studies reporting mortality and persistent bacteraemia We used funnel plots with Egger re-gression test to assess publication bias (P lt 01)

All statistical analyses were per-formed with R software version 340 (R Foundation for Statistical Computing Vienna Austria) using the Meta and Metafor meta-analysis packages

Prevalence study

We obtained data on the prevalence of extended-spectrum β-lactamase-associated infection from the same studies included in the meta-analysis We also made a search for other data sources in the published and grey lit-erature (Box 1) We included data on children (ages 0ndash21 years) where avail-able and all age groups if data for these ages were unavailable We calculated percentage prevalence by the number of people or isolates testing positive for extended-spectrum β-lactamases out of the total population or isolates tested For casendashcontrol studies the overall prevalence rate was extracted instead Numbers of cases and samples were extracted if stated by the source Where population maps were provided in the source material the average of the range were extracted as the prevalence in the country We pooled the prevalence data by calculating the mean of the extracted data from all sources for each country

ResultsMeta-analysis

Study selection and characteristics

The database search yielded 6665 ar-ticles We removed 1089 duplicates and excluded a further 3046 studies after

Box 1 Search strategy used in the systemic review of extended-spectrum β-lactamase-associated infection among children and young adults in South-East Asia and Western Pacific countries

We searched online databases (Embasereg MEDLINEreg Cochrane Library Web of Science Scopus OvidSPreg EBSCO) electronic abstract databases and references in published articles For the prevalence study we also searched the grey literature including the websites of the World Health Organization and the United States Centers for Disease Control surveillance systems related to antimicrobial resistance dissertations conference reports and country reports When more information about studies was needed we contacted authors or website administrators

We used the following keywords

extended-spectrum beta-lactamase OR extended-spectrum beta-lactamase OR ESBL OR ESBLs OR ESBL-producing

AND paediatric OR pediatric OR juvenile OR child OR children OR adolescence OR infant OR neonat OR neonatal OR newborn OR nursery

AND Asia OR Asia Pacific OR South Asia OR The Western Pacific OR South-East Asia OR Australia OR Bangladesh OR Bhutan OR Brunei Darussalam OR Cambodia OR China OR Cook Islands OR Democratic Peoples Republic of Korea OR Fiji OR India OR Indonesia OR Japan OR Kiribati OR Lao Peoples Democratic Republic OR Malaysia OR Maldives OR Marshall Islands OR Federated States of Micronesia (Federated States of ) OR Mongolia OR Myanmar OR Nauru OR Nepal OR New Zealand OR Niue OR Palau OR Papua New Guinea OR Philippines OR Republic of Korea OR Samoa OR Singapore OR Solomon Islands OR Sri Lanka OR Thailand OR Timor-Leste OR Tonga OR Tuvalu OR Vanuatu OR VietNam

488 Bull World Health Organ 201997486ndash501B| doi httpdxdoiorg102471BLT18225698

Systematic reviewsAntibiotic resistance in Asia Pacific children Yanhong Jessika Hu et al

screening titles and abstracts After as-sessing the full text of 577 studies we excluded 537 Screening of reference lists and conference abstracts yielded no additional studies In total 40 stud-ies were included in the meta-analysis (Fig 1) Three studies were reported in Chinese language one study each in Korean and French and the remaining 35 were in English

Overall the 40 studies reported 46 960 bacterial isolates from 17 829 children providing samples We pooled data from 2411 samples testing positive and 2874 testing negative for extended-spectrum β-lactamase-producing bac-teria over the study period up to June 2018 The most common method of detection of bacterial phenotypes was agar disk diffusion in 32 studies The study designs were 11 retrospective cohort studies 14 prospective cohort studies six observational studies two cross-sectional studies and seven casendashcontrol studies We found stud-ies from 11 different countries and areas Taiwan China India Indonesia Japan Malaysia Republic of Korea Singapore Sri Lanka Thailand and Viet Nam In 15 studies the focus was specifically on neonates (lt 28 days old) 15 studies were of age groups 0ndash21 years (excluding neonates) seven studies were of age 0ndash5 years (exclud-ing neonates) and three studies did not specify the ages (Table 1 available at httpwwwwhointbulletinvol-umes96718-225698)

Risk factors

The risk of infection with extended-spectrum β-lactamase-producing bac-teria was significantly higher for pa-tients whose medical history included intensive care unit admission (OR 65 95 CI 304 to 1373 I2 65 six stud-ies) hospitalization (OR 33 95 CI 195 to 557 I2 80 11 studies) or surgery (OR 23 95 CI 141 to 381 I2 25 six studies Table 2)

The risk of infection was higher for patients with co-existing bacteraemia (OR 53 95 CI 364 to 772 I2 38 six studies) nosocomial infections (OR 52 95 CI 223 to 1207 I2 92 two studies) lower respiratory tract infec-tions (OR 50 95 CI 1350 to 719 I2 79 four studies) sepsis (OR 46 95 CI 334 to 635 I2 80 10 stud-ies) or recurrent urinary tract infections (OR 20 95 CI 161 to 243 I2 90 11 studies Table 2)

Antibiotics associated with risk of infection included third-generation cephalosporins (OR 48 95 CI 225 to 1027 I2 89 11 studies) vancomycin (OR 34 95 CI 221 to 520 I2 0 three studies) and quinolones (OR 30 95 CI 104 to 863 I2 79 five studies) Five studies reported that appropriate initiation of empirical antibiotics was protective showing a pooled OR of infection of 029 (95 CI 011 to 079 I2 65 five studies Table 2)

Exposure to continuous positive airway pressure therapy was not signifi-cantly associated with a risk of infection (OR 34 95 CI 054 to 2061 three studies) Other types of invasive life support were a risk however The OR for total parenteral nutrition was 38 (95 CI 135 to 1056 five studies) For mechanical ventilation the OR was 33 (95 CI 103 to 1053 six studies) and for endotracheal intubation 21 (95 CI 122 to 349 eight studies) Central venous catheterization had an OR of 17 (95 CI 100 to 285 nine studies Table 2)

Treatment outcomes

Most specimens from patients with extended-spectrum β-lactamase-producing bacterial infection showed

resistance to multiple antibiotics The risk of antibiotic resistance was highest for extended-spectrum β-lactamase-positive patients treated with cepha-losporins (OR 705 95 CI 4325 to 11502 I2 83 25 studies) and lowest with cotrimoxazole (OR 18 95 CI 135 to 247 I2 43 15 studies) The ORs for resistance to tetracyclines and nitrofurantoin were not statistically significant (Table 3)

The duration of fever was 061 days longer in patients with extended-spectrum β-lactamase-producing bac-teria than patients without (95 CI 018 to 072 I2 92 seven studies Fig 2) Pooling five studies we found that persistent bacteraemia was four times higher in patients positive for extended-spectrum β-lactamase-producing bacteria (95 CI 266 to 614 I2 0 Fig 3) Results from eight studies showed that the mean difference in length of hospital stay was 259 days (95 CI 1281 to 3889 I2 100) for patients with extended-spectrum β-lactamase-associated infec-tion than those without such infection (Fig 4) Subgroup analysis showed that the mean length of hospital stay associated with infection was 29 days longer for patients who had recently

Fig 1 Flow diagram of the systematic review of extended-spectrum β-lactamase-associated infection among children and young adults in South-East Asia and Western Pacific countries

6450 articles identified through database searching (Embasereg MEDLINEreg Cochrane Library Web of ScienceTM Scopus OvidSPreg EBSCO)

215 articles identified through other sources

5576 articles after 1089 duplicates removed 3046 articles excludedbull 1460 not conducted in WHO South-East

Asia or Western Pacific Regionsbull 1586 not pediatric population

1953 articles excludedbull 1001 molecular or genetic studiesbull 952 not comparing ESBL-positive and

negative infections

537 full-text articles excludedbull 230 not conducted in WHO South-East

Asia or Western Pacific Regionsbull 186 without ESBL negative infectionsbull 90 without pediatric databull 14 molecular mechanism studiesbull 12 without full textbull 3 pharmaceutical studiesbull 2 review articles

2530 articles screened

577 full-text articles assessed for eligibility

40 studies included in quantitative synthesis (meta-analysis)

EBSL extended-spectrum β-lactamase-producing bacteria WHO World Health Organization



been admitted to an intensive care unit care than the patients not receiving this care Similar results were seen for invasive life support the mean length of stay after central venous catheteriza-tion was 33 days longer than without catheterization59

Eleven studies reported a pooled number of 188 deaths among 565 patients with extended-spectrum β-lactamase-associated infections com-pared with 86 deaths in 745 patients

without these infections (OR 32 95 CI 182 to 580 I2 49 Fig 5) When analysed by subgroups the risk of death for patients who had previ-ously been admitted to the intensive care unit or exposed to central venous catheterization were not significant However the risk of death was higher among patients with sepsis (OR 49 95 CI 211 to 1139 I2 38) than those without sepsis (OR 23 95 CI 119 to 426 I2 35)59

We also looked at the ORs for neonates and non-neonates but the differences not statistically significant between these groups59

Validity tests

None of the factors we analysed by meta-regression were contributors to between-study heterogeneity In the Newcastle-Ottawa analysis of risk of bias we found that 60 (24 out of 40) of studies scored high on risk of

Table 2 Pooled risk of extended-spectrum β-lactamase-associated infection among children and young adults in South-East Asia and Western Pacific countries by medical history and co-morbid conditions 2002ndash2018

Subgroup No of studies

Total no of patients

ESBL-positive no ESBL-negative no Pooled OR (95 CI)a I2

Events Total Events Total

Received medical care in previous 3 months Recent intensive care unit stay

6 1258 124 399 65 859 646 (304 to 1373) 65

Recent hospitalization 11 2936 318 727 367 2209 330 (195 to 557) 80Recent surgery 6 1178 58 433 37 745 232 (141 to 381) 8Pre-infection hospitalization

3 223 NA 110 NA 113 1142b (minus786 to 3071) 99

Diagnosis of co-morbid or underlying conditionsBacteraemia 6 958 103 222 109 736 530 (364 to 772) 38Lower respiratory tract infection

4 837 213 395 134 442 501 (350 to 719) 79

Recurrent urinary tract infection

11 2149 355 808 328 1341 201 (167 to 243) 90

Nosocomial infection 2 114 40 55 21 59 519 (223 to 1207) 92Various diagnoses 7 1772 229 545 339 1227 268 (206 to 348) 79Sepsis 10 970 397 550 146 420 461 (334 to 635) 80Received antibiotics in the previous 3 monthsThird-generation cephalosporin

11 2318 384 777 249 1541 481 (225 to 1027) 89

Vancomycin 3 813 69 235 79 578 339 (221 to 520) 0Quinolone 5 1242 105 477 55 765 299 (104 to 863) 79Carbapenem 5 1156 68 405 49 751 285 (147 to 553) 42Aminoglycoside 7 1444 151 485 235 959 284 (121 to 665) 83Penicillin 9 1750 380 798 249 952 287 (110 to 747) 92Received antibiotic prophylaxis

4 703 84 238 132 465 182 (116 to 286) 0

Received any antibiotic

13 2289 340 584 457 1705 358 (230 to 557) 60

Received appropriate empirical antibiotic therapy

5 803 102 192 463 611 029 (011 to 079) 65

Exposed to invasive life support Total parenteral nutrition

5 805 216 283 350 522 377 (135 to 1056) 79

Continuous positive airway pressure

3 682 148 241 303 441 335 (054 to 2061) 91

Mechanical ventilation 6 1098 137 432 271 666 329 (103 to 1053) 83Endotracheal intubation 8 1157 187 407 347 750 206 (122 to 349) 61Central venous catheter 9 957 244 352 429 605 169 (100 to 285) 41

CI confidence interval EBSL extended-spectrum β-lactamase-producing bacteria NA not applicable OR odds ratioa MantelndashHaenszel random-effects b Pre-infection hospitalization is the time of hospitalization to the time while patients with confirmed infection with extended-spectrum β-lactamase-producing

Enterobacteriaceaeis expressed as mean difference in days between positive and negative patients (standard deviation)



Table 3 Pooled risk of antibiotic resistance to extended-spectrum β-lactamase-producing bacteria in specimens from children and young adults in South-East Asia and Western Pacific countries by antibiotic class 2002ndash2018

Antibiotic class No of studies

Total no of

patients

ESBL-positive ESBL-negative Pooled OR (95 CI)a I2


Cephalosporins 25 3444 1339 1483 632 1961 7050 (4325 to 11502) 83Monobactams 8 879 274 412 63 467 4116 (1405 to 12055) 58Penicillins 24 3148 1160 1304 1091 1844 1941 (867 to 4346) 86Aminoglyclosides 25 3449 495 1452 276 1997 571 (342 to 954) 74Combinationsb 22 2993 706 1141 739 1852 437 (195 to 982) 91Carbapenems 22 2940 79 1244 64 1696 399 (168 to 948) 0Fluoroquinolones 25 3351 627 1439 607 1912 333 (214 to 517) 78Cotrimoxazole 15 2346 547 868 755 1478 182 (135 to 247) 43Tetracyclines 7 1447 355 619 357 828 158 (076 to 330) 81Nitrofurantoin 3 1039 58 423 90 6 097 (064 to 146) 14

CI confidence interval EBSL extended-spectrum β-lactamase-producing bacteria OR odds ratioa MantelndashHaenszel random-effectsb Combinations Ampicillin + sulbactam ticarcillin + clavulanic acid amoxicillin + clavulanate cefoperazone + sulbactam piperacillin + tazobactam ceftazidime+

clavulanic acid

Fig 2 Duration of fever after antibiotic therapy among children and young adults with and without extended-spectrum β-lactamase-associated infection in South-East Asia and Western Pacific countries

ESBL-positive ESBL-negative Study Mean SD Total Mean SD Total Weight Mean difference 95CI Mean difference 95CI

Fan et al 2014 400 290 104 190 140 208 182 210 (151ndash269)Han et al 2015 200 007 22 200 149 189 254 000 (-021ndash021)Han et al 2015 550 820 21 500 820 40 10 050 (-383ndash483)Amornchaicharoensuk et al 2016

3500 3400 19 2900 2200 69 01 600 (-1015ndash2215)

Kim et al 2017 200 110 31 150 060 154 221 050 (010ndash090)Tsai et al 2017 200 013 14 180 006 27 268 020 (013ndash027)Kim et al 2019 270 420 32 190 160 66 65 080 (-071ndash231)

Total (95 CI) 243 753 061 (017ndash105)Heterogeneity Tau2 = 019 Chi2 = 4644 df = 6 (P lt 001) I2 = 87 Test for overall effect Z = 270 (P lt 001) Favours ESBL-negative Favours ESBL-positive

-10 5 0 5 10

CI confidence interval EBSL extended-spectrum β-lactamase-producing bacteria SD standard deviation Note We made inverse variance (IV) random-effects

Fig 3 Persistent bacteraemia among children and young adults with and without extended-spectrum β-lactamase-associated infection in South-East Asia and Western Pacific countries

ESBL-positive ESBL-negativeStudy Events Total Events Total Weight OR 95CI OR 95CI

Fan et al 2014 49 104 35 208 623 440 (259ndash748)Han et al 2015 3 21 3 40 61 206 (038ndash1121)Tsai et al 2016 7 77 11 316 181 277 (104ndash741)Kim et al 2017 7 31 7 154 136 612 (197ndash1902)

Total (95 CI) 233 718 1000 405 (266ndash614)Heterogeneity Tau2 = 0 Chi2 = 179 df = 3 (P = 062) I2 = 0 Test for overall effect Z = 656 (P lt 001) Favours ESBL-negative Favours ESBL-positive

01 02 05 1 2 5 20

CI confidence interval EBSL extended-spectrum β-lactamase-producing bacteria OR odds ratioNote We made MantelndashHaenszel random-effects



bias and 40 were low risk (Table 4 Table 5) Only four studies had clear statements about comparability and 10 about representativeness The results from Eggerrsquos regression test revealed that publication bias was significant (P lt 0001) Sensitivity analysis exclud-ing small studies with samples less than 10 revealed that the funnel plots were consistently asymmetric (P lt 0001 available from the corresponding au-thor) The sensitivity analysis showed that the data were not consistent with from the overall estimated ORs and similar trends were observed This eval-uation showed that a more restricted analysis of the data did not affect the magnitude direction and the overall summary estimate

Prevalence study

The overall pooled prevalence of extend-ed-spectrum β-lactamase in the studies included the meta-analysis combined with surveillance reports was 253 The pooled prevalence from the studies in the meta-analysis was 39 among the 31 studies conducted in hospital settings and 31 in the seven studies conducted in community settings (two studies were in both hospital and the community)

Using data from other sources we mapped population surveillance data from a total of 21 countries and areas in the South-East Asia and the Western Pacific Regions (Table 6) The pooled data from all available surveillance resources that included adults and chil-

dren showed that India had the highest pooled prevalence (900) and Austra-lia the lowest (36 numerators and denominators unavailable) The pooled data specifically for children where available from surveillance resources and published data showed similar results (Fig 6)

DiscussionThis study revealed that the average combined prevalence of infection with extended-spectrum β-lactamase-producing bacteria among children in South-East Asia and the Western Pacific is high Risk factors for infection includ-ed recent intensive care unit admission hospitalization surgery or antibiotic

Fig 4 Length of hospital stay among children and young adults with and without extended-spectrum β-lactamase-associated infection in South-East Asia and Western Pacific countries

ESBL-positive ESBL-negativeStudy Mean SD Total Mean SD Total Weight Mean difference 95CI Mean difference 95CI

Boo et al 2005 2300 2900 80 400 300 80 125 1900 (1261ndash2539)Kuo et al 2007 7280 850 54 2625 440 54 128 4655 (4400ndash4910)Shakil et al 2010 3500 2300 104 2500 2200 107 125 1000 (392ndash1608)Vijayakanthi et al 2013 6300 520 8 1700 020 39 127 4600 (4240ndash4960)Fan et al 2014 1820 1348 104 590 440 208 128 1230 (964ndash1496)Han et al 2015 6337 197 21 1700 019 40 128 4637 (4553ndash4721)Tsai et al 2016 7467 5600 71 6733 5017 289 111 734 (-691ndash2159)Tsai et al 2017 2917 282 14 1278 041 27 128 1639 (1490ndash1788)


-20 0 20 40 60

CI confidence interval EBSL extended-spectrum β-lactamase-producing bacteria SD standard deviationNote We made inverse variance (IV) random-effects

Fig 5 Mortality among children and young adults with and without extended-spectrum β-lactamase-associated infection in South-East Asia and Western Pacific countries


Jain et al 2003 110 165 4 36 120 1600 (539ndash4752)Kuo et al 2007 8 54 7 54 119 117 (039ndash348)Lee et al 2007 19 35 9 54 131 594 (224ndash1577)Sehgal et al 2007 9 38 1 25 54 745 (088ndash6303)Shakil et al 2010 3 104 0 107 32 741 (038ndash14532)Gaurav et al 2011 13 50 4 52 110 422 (127ndash1400)Vijaykanthi et al 2013 2 8 6 39 68 183 (030ndash1133)Han et al 2015 3 21 4 40 80 150 (030ndash743)Tsai et al 2016 14 71 36 289 161 173 (087ndash341)Chiu et al 2017 4 5 11 22 47 400 (038 to 4174)Tsai et al 2017 3 14 4 27 77 157 (030ndash825)


01 02 05 1 2 5 100




exposure and co-existing bacteraemia nosocomial infections lower respira-tory tract infections sepsis or recurrent urinary tract infections Infection was associated with higher mortality higher morbidity and longer hospitalization

The prevalence of infection we found in South-East Asia and the Western Pacific countries are similar to those reported from other surveillance systems worldwide64although many locations do not report data for children A review of worldwide trends in extend-ed-spectrum β-lactamase-associated infection reported higher prevalence in Asia Latin America and the Middle East (from 28 to 40) compared with other higher-income areas (from 8 to 12)64

As many of the studies we found were hospital-based our results sup-port the need for resources and policies for control of nosocomial infection A recently published modelling study showed that antibiotic use in hospital is a major driver for antimicrobial resis-tance in human infection compared with animal and environmental antibiotic exposures65 Although infection control and hygiene may be sub-optimal in the countries we studied infection control is easier to manage within health-care institutions than in other unstructured systems such as animal husbandry and the environment Without proper control of antimicrobial resistance in hospitals patients can disseminate an-tibiotic residues and resistance genes to the community and environment This still highlights the importance of hos-pital-based stewardship for controlling antibiotic use and how this stewardship can reduce the risk of developing multi-drug resistant organisms66 At the same time the rising community prevalence of extended-spectrum β-lactamase-associated infection provides evidence for expanding prevention to other set-tings3

Our meta-analysis showed that recent medical care including intensive care unit stays hospitalization surgery and antibiotic therapy was associated with increased risk of infection These results suggest that children may ac-quire such infections during health care especially when undergoing inva-sive procedures Specifically children who had exposure to third-generation cephalosporins carbapenems and fluo-roquinolones had three to four times greater risk for extended-spectrum β-lactamase-associated infection which Ta

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e m

ade

Man

tel-H

aens

zel r

adom

-effe

cts



Tabl

e 5

Ri

sk o

f bia

s in

coho

rt st

udie

s inc

lude

d in

the

met

a-an

alys

is of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n am

ong

child

ren

and

youn

g ad

ults

in So

uth-

East

Asia

and

Wes

tern

Pac

ific

coun

trie

s 20

02ndash2

018

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal

scor

eb

Repr

esen

tativ

enes

s of

the

expo

sed

coho

rt

Sele

ctio

n of

the

non-

expo

sed

coho

rt

Asce

rtai

nmen

t of

exp

osur

eDe

mon

stra

tion

that

ou

tcom

e of

inte

rest

w

as n

ot p

rese

nt a

t the

st

art o

f stu

dy

Coho

rts a

re

com

para

ble

base

d on

the

desig

n or

an

alys

is

Asse

ssm

ent o

f ou

tcom

ea

Follo

w -u

p lo

ng

enou

gh fo

r ou

tcom

es to

occ

ur

Adeq

uacy

of

follo

w-u

p of

co

hort

s

Kim

et a

l 20

0220

00

10

01

11

4Ja

in e

t al

2003

210

01

00

11

14

Chiu

et a

l 20

0523

10

10

01

11

5H

uang

et a

l 20

0724

00

10

01

11

4Ja

in amp

Mon

dal 2

00725

00

10

01

11

4Le

e et

al

2007

271

01

00

11

15

Sehg

al e

t al

2007

280

01

00

11

14

Bhat

tach

arje

e et

al

2008

290

01

00

11

14

Anan

dan

et a

l 20

0930

00

10

01

11

4Ki

m e

t al

2009

310

01

00

11

14

Shak

il et

al

2010

321

01

00

11

15

Liu

et a

l 20

1134

00

10

01

11

4W

ei e

t al

2011

350

01

00

11

14

Zhen

g et

al

2012

370

01

00

11

14

Vija

yaka

nthi

et a

l 20

1338

00

10

01

11

5Th

emph

acha

na e

t al

2014

400

01

00

11

14

Duo

ng e

t al

2015

430

01

00

11

14

Han

et a

l 20

1517

c0

01

00

11

14

Han

et a

l 20

1544

d0

01

00

11

14

Nish

a et

al

2015

450

01

01

11

15

Agar

wal

et a

l 20

16 46

0

01

00

11

14

Amor

ncha

icha

roen

suk

20

1647

00

10

11

11

5

He

et a

l 20

1751

10

10

01

11

5Ki

m e

t al

2017

521

01

00

11

15

Man

dal e

t al

2017

530

01

01

11

04

Nish

a et

al

2017

540

01

00

11

14

Tsai

et a

l 20

1755

10

00

01

11

4W

eera

singh

e et

al

2018

580

11

00

11

04

a Sub

ject

s in

diffe

rent

out

com

e gr

oups

are

com

para

ble

bas

ed o

n th

e st

udy

desig

n or

ana

lysis

Con

foun

ding

fact

ors a

re c

ontro

lled

b Max

imum

scor

e 8

C N

eutro

poen

ia st

udy

d Urin

ary

tract

infe

ctio

n st

udy

Not

es W

e ap

plie

d th

e N

ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

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d le

2 as

hig

h



is similar to previous reports2667ndash71 As these antibiotics are primarily used for treating severe infections their use may be a marker for disease severity rather than a direct contributor to developing resistance Nevertheless if excessive fluoroquinolone use does contribute to emergence of resistant bacteria this adds another reason to avoid the unnecessary use of these broad-spectrum antibiotics in children

Coexisting illnesses including bac-teraemia nosocomial infection lower

respiratory tract infections sepsis and recurrent urinary tract infections were associated with increased risk of infec-tion These co-morbidities could be risk factors for use of invasive treatments such as a central venous catheterization mechanical ventilation intravenous nutrition or increased risk of interac-tions with health-care settings In a two-centre casendashcontrol study of risk factors for infection with extended-spectrum β-lactamase-producers in children mul-tivariable analysis identified sepsis and

neurological illnesses as potential risk factors which supports our findings72 Previously published studies among both young adults and children found that prolonged hospital stay or pro-longed use of invasive medical devices were associated with infection by or be-ing colonized with extended-spectrum β-lactamase-producing bacteria266971 which is consistent with our findings

Recent surgery and antibiotic pro-phylaxis were associated with extended-spectrum β-lactamase infection in our

Table 6 Pooled prevalence of overall population of extended-spectrum β-lactamase-associated infection from available surveillance data in 20 South-East Asia and Western Pacific countries or areas

Country or area Data sourcea Prevalence in childrenb by data source

Prevalence in children and adultsc by data source

Pooled preva-lence

No of people

No () ESBL-positive

No of people

No () ESBL-positive

Australia SENTRY 1998ndash199960 NA NA 660 8 (12) 36SMART 201161 80 2 (25) 80 2 (25)CDDEP 2011ndash201410 NA NA NR NR (45)AURA 201562 NA NA NR NR (60)

Bhutan CDDEP 2011ndash201410 NA NA NR NR (295) 295Brunei Darussalam CDDEP 2011ndash201410 NA NA NR NR (45) 45Cambodia CDDEP 2011ndash201410 NA NA NR NR (495) 495China SENTRY 1998ndash199961 NA NA 247 63 (255) 475

CDDEP 2011ndash201410 NA NA NR NR (695)China Hong Kong Special Administrative Region

SENTRY 1998ndash199961 NA NA 324 43 (133) 133

Taiwan China SENTRY 1998ndash199961 NA NA 139 11 (79) 79India CDDEP 2011ndash201410 NA NA NR NR (900) 900Japan SENTRY 1998ndash199961 NA NA 272 18 (66) 106

CDDEP 2011ndash201410 NA NA NR NR (145)Malaysia CDDEP 2011ndash201410 NA NA NR NR (145) 145Federated States of Micronesia (Federated States of )

CDDEP 2011ndash201410 NA NA NR NR (695) 695

Myanmar CDDEP 2011ndash201410 NA NA NR NR (695) 695Nepal CDDEP 2011ndash201410 NA NA NR NR (295) 295New Zealand CDDEP 2011ndash201410 NA NA NR NR (45) 37

ESR 201663 NR NR (28) NR NR (28)Papua New Guinea CDDEP 2011ndash201410 NA NA NR NR (295) 295Philippines SENTRY 1998ndash199961 NA NA 298 58 (195) 245

CDDEP 2011ndash201410 NA NA NR NR (295)Republic of Korea CDDEP 2011ndash201410 NA NA NR NR (295) 295Singapore SENTRY 1998ndash199961 NA NA 153 31 (203) 203Thailand CDDEP 2011ndash201410 NA NA NR NR (295) 295Viet Nam SMART 201161 38 15 (395) 38 15 (395) 545

CDDEP 2011ndash201410 NA NA NR NR (695)

EBSL extended-spectrum β-lactamase NA not applicable NR not reporteda Data sources AURA Antimicrobial Use and Resistance in Australia Surveillance System CDDEP Center for Disease Dynamics Economics amp Policy ESR Institute

of Environmental Science and Research Surveillance System in New Zealand SENTRY Antimicrobial Surveillance Program by JMI Laboratories SMART Study for Monitoring Antimicrobial Resistance Trends

b Ages 0ndash21 years c Ages not specified

Notes We searched the published and grey literature for surveillance data from all Member States and areas in the World Health Organization South-East Asia and Western Pacific Regions No data were available for Bangladesh Cook Islands Democratic Peoples Republic of Korea Fiji Indonesia Kiribati Lao Peoples Democratic Republic Maldives Marshall Islands Mongolia Nauru Niue Palau Samoa Solomon Islands Timor-Leste Tonga Tuvalu and Vanuatu



Fig

6

Map

of p

reva

lenc

e of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s

087

517

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kmN

Prev

alen

ce o

f ES

BL-a

ssoc

iate

d in

fect

ion

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060

ndash40

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ndash0N

o da

ta

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ts an

d ch

ildre

nCh

ildre

n

ESBL

ext

ende

d-sp

ectru

m β

-lact

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eN

otes

We

pool

ed d

ata

from

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arch

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he p

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hed

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re fo

r sur

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ance

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r Sta

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orld

Hea

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s Th

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nd c

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incl

udes

dat

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n B

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i Dar

ussa

lam

Cam

bodi

a Ta

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na C

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Hon

g Ko

ng S

peci

al A

dmin

istra

tive

Regi

on I

ndia

Ind

ones

ia J

apan

Fed

erat

ed S

tate

s of M

icro

nesia

(Fed

erat

ed S

tate

s of)

Mya

nmar

Nep

al N

ew Z

eala

nd

Papu

a N

ew G

uine

a P

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s Re

publ

ic o

f Kor

ea S

inga

pore

Tha

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and

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t Nam

The

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ren

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(age

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ars)

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udes

dat

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m A

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) Ch

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an C

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7)

Indi

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) In

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) Ja

pan

(90

)

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)

Repu

blic

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orea

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apor

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i Lan

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aila

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et N

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)



study Others have shown that surgical antibiotic prophylaxis increases the risk for antimicrobial resistance and acquisition of infection73 One study from Switzerland found that half of all surgical ward prescriptions (680 out of 1270) were inappropriate74 Antibi-otic stewardship programmes have been shown to improve surgical antibiotic prophylaxis and treatment of surgical site infections75

Our study found that initiation of appropriate empirical antibiotics was protective against extended-spectrum β-lactamase-associated infection indi-cating the importance of thoughtful se-lection of antibiotics The details of this finding warrant further study The risk is especially high for critically ill patients requiring surgery or intensive care and who need antibiotics urgently before susceptibility has been established but who are also at increased risk for drug-resistant infections Therefore antibiotic stewardship programmes and guidelines in health-care facilities fill an important function Furthermore as studies in Asia have shown a high prevalence of easy access to unsupervised antibiotics within the community more attention is needed to improving appropriate antibiotic use through training educa-tion policy and regulation outside of hospitals76

Children infected with extended-spectrum β-lactamase-producers had significantly longer length of hospital stays (26 days) and required more in-tensive care unit days (29 days) than those without such infection This leads to higher health-care costs77 in addition to the costs to society in terms of family and community pressures and lost pro-ductivity At the same time prolonging intensive care unit and hospital stays increases the risk of further acquisition and transmission of drug resistance

Mortality and persistent bacter-aemia were three to four times higher for patients infected with extended-spectrum β-lactamase-associated in-fections than those without This adds to the economic and social burden of these infections Based on our meta-regression the study location study design patientrsquos diagnosis sex or intensive care unit stay did not influ-ence mortality This implies that worse outcomes may be directly attributable to the presence of extended-spectrum β-lactamase-associated infection The severity of the diseases associated with

these infections might also contribute to mortality risk as the patients diagnosed with sepsis had higher risk of mortality than those without sepsis However we were unable to determine for each study whether other factors may have influ-enced outcomes because comprehensive information was not available

One of the strengths of our study was the comprehensive data collec-tion strategy which provided a high sample size and study power Second two different tools were used to assess for bias which together with risk fac-tor and outcomes sensitivity analysis strengthened the studyrsquos validity and reliability Third we assessed previous antibiotic history with different anti-biotic categories providing a detailed insight into the link between antibiotic use and resistance Fourth we also con-ducted meta-regression to determine if other factors might have influenced treatment outcomes This established association between patientsrsquo mortality length of stay and extended-spectrum β-lactamase infections

There were several limitations to this study The distribution of studies between locations was not uniform Of the 48 Member States and areas in the South-East Asia and the Western Pacific Regions we were able to find and ex-tract data for the meta-analysis from 12 countries For prevalence estimates we added surveillance data from 10 other countries and areas but we found data on 0ndash21-years-olds for only three countries with available paediatric data which might underestimate the real situation among children Moreover although we made subgroup analyses most of the pooled prevalence from selected stud-ies were from hospital settings Most of the surveillance sources reported only prevalence without denominators and numerators Nevertheless the study provides a rough indication of the extent of extended-spectrum β-lactamase-associated infection and highlights the need for establishment of surveillance systems in these Regions We can ex-pect that within large Regions rates of infection are unlikely to be homogenous particularly where there are large urban and rural disparities Among 40 studies only seven were community based This might have underestimated antibiotic resistance in the community With the rising concern for community-acquired infections and reports of increased rates of faecal colonization with extended-

spectrum β-lactamase-producing bacte-ria in healthy children risk factors might not only arise from hospital influences but also from community exposure and international travel78ndash80 Because of limited information in the articles we are unable to determine whether longer hospitalization increased the risk of infections or vice versa Both situations are likely and further studies are needed to clarify the associations

Another limitation we faced was the lack of laboratory standardization for the identification of the extended-spectrum β-lactamase-producer phe-notypes Quality and standardization may vary between laboratories although most followed Clinical and Laboratory Standards Institute guidelines Sensitiv-ity analyses found that use of different laboratory guidelines or test methods or the study year did not affect our results All studies used phenotypic methods as opposed to the gold standard through genotyping with the majority using agar double-disk diffusion test while a few studies used the Vitekreg system (bio-Meacuterieux Marcy lrsquoEtoile France) Thus detection rates could be underestimated

We hope this study will provide im-portant information for policy-makers who need to allocate resources to im-prove surveillance monitor treatment outcomes improve infection control in intensive care unit and surgery wards and develop policies for the use of empirical and prophylactic antibiotics Knowledge of resistance rates can guide treatment recommendations Countries without established antibiotic steward-ship programmes should prioritize these activities along with public education programmes With very high burden of neonatal sepsis 042 million (39) of the total 109 million deaths related with sepsis in these Regions81 scaling up strategies to prevent infection and encourage appropriate treatment for this vulnerable group is needed More studies are also needed to measure the impact of antimicrobial resistance in children

AcknowledgementsWe thank Dan Yu

Competing interests None declared



摘要20 国和地区儿科患者中使用超广谱 β- 内酰胺酶产生肠杆菌科抗生素耐药性证据系统评价和荟萃分析目的对世卫组织东南亚和西太平洋区域儿童和青年人的超广谱 β 内酰胺酶相关感染的风险因素结果和感染率情况进行了系统审查方法截至 2018 年 6 月我们于在线数据库中搜索了 0-21 岁个体中超广谱 ββ 内酰胺酶肠杆菌科感染相关的已发表的研究我们包含了报告患者此类组织的阳性和阴性状态的病例对照队列研究横断面研究和观察性研究对于荟萃分析我们采用风险因素和感染结果的随机效应进行建模并分析亚组元回归我们使用现有监测数据绘制了 20 国和地区感染率情况图结果扫描的 6665 篇文章中我们在荟萃分析中纳入了来自 11 个国家和地区的 40 项研究汇总研究包括

2411 个检测阳性样本和 2874 个检测阴性样本超广谱ββ 内酰胺酶细菌感染风险较高与先前住院治疗有关特别是重症监护室住院（合并 OR 6595 置信区间CI 304 至 1373）抗生素暴露（特别是第三代头孢菌素OR 4895 置信区间CI 225至 1027）和某些共存疾病实证抗生素治疗可预防感染（OR 02995 置信区间CI 011 至 079)感染患者住院时间较长（26 天 95 置信区间CI 1281 至 3889）并伴有更高的死亡风险（OR 3295 置信区间CI 182 至 580)这些地区人口感染率极高且儿童监测数据骇人结论世卫组织东南亚和西太平洋区域的国家和地区需采取抗生素管理政策用以预防感染并鼓励适当治疗

Reacutesumeacute

Donneacutees disponibles concernant la reacutesistance aux antibiotiques des enteacuterobacteacuteries productrices de becircta-lactamases agrave spectre eacutelargi chez des patients peacutediatriques dans 20 pays et reacutegions revue systeacutematique et meacuteta-analyseObjectif Reacutealiser une revue systeacutematique des facteurs de risque des conseacutequences et de la preacutevalence des infections agrave becircta-lactamases agrave spectre eacutelargi chez des enfants et des jeunes adultes dans les reacutegions de lrsquoAsie du Sud-Est et du Pacifique occidental de lrsquoOrganisation mondiale de la Santeacute (OMS)

Meacutethodes Jusqursquoen juin 2018 nous avons consulteacute des bases de donneacutees en ligne agrave la recherche drsquoeacutetudes publieacutees portant sur des infections par des enteacuterobacteacuteries productrices de becircta-lactamases agrave spectre eacutelargi chez des individus acircgeacutes de 0 agrave 21 ans Nous avons inclus des eacutetudes casteacutemoins de cohortes transversales et drsquoobservation rendant compte de patients positifs et neacutegatifs agrave lrsquoeacutegard de ces organismes Pour la meacuteta-analyse nous avons utiliseacute une modeacutelisation agrave effets aleacuteatoires des facteurs de risque et des conseacutequences associeacutes

aux infections et une meacuteta-reacutegression pour lrsquoanalyse des sous-groupes Nous avons analyseacute la preacutevalence de ces infections dans 20 pays et reacutegions agrave lrsquoaide des donneacutees de surveillance disponibles

Reacutesultats Sur les 6665 articles parcourus nous avons inclus 40 eacutetudes de 11 pays et reacutegions dans la meacuteta-analyse Prises ensemble les eacutetudes incluaient 2411 eacutechantillons deacuteclareacutes positifs et 2874 neacutegatifs Un risque plus eacuteleveacute drsquoinfection due agrave des bacteacuteries productrices de becircta-lactamases agrave spectre eacutelargi a eacuteteacute associeacute agrave de preacuteceacutedents soins hospitaliers et en particulier agrave des seacutejours en uniteacute de soins intensifs (RC regroupeacutes 65 IC agrave 95 de 304 agrave 1373) agrave une exposition aux antibiotiques (en particulier aux ceacutephalosporines de troisiegraveme geacuteneacuteration CR 48 IC agrave 95 de 225 agrave 1027) et agrave certaines affections concomitantes Le traitement antibiotique empirique a eu un effet

ملخصالدليل املتاح عىل مقاومة املضادات احليوية من الطفيليات املعوية ممتدة النطاق املنتجة لبيتا الكتاميز يف املرىض من األطفال

يف 20 دولة ومنطقة مراجعة منهجية وحتليل تلويالغرض إجراء مراجعة منهجية عوامل خطر ونتائج وانتشار طيف العدوى ممتدة النطاق املرتبطة ببيتا الكتاميز املمتد يف مناطق جنوب

رشق آسيا وغرب املحيط اهلادي التابعة ملنظمة الصحة العامليةالدراسات عىل اإلنرتنت بيانات قواعد يف بالبحث قمنا الطريقة املعوية بالطفيليات اإلصابة حول 2018 يونيو حتى املنشورة من ــراد األف يف الكتاميز بلبيتا املنتجة النطاق ممتدة املنتجة احلاالت مراقبة دراسات بتضمني قم عاما 21 وحتى الوالدة واملجموعات والدارسات متعددة القطاعات والدراسات القائمة عىل املالحظة والتي تعد تقارير حول مدى إجيابية أو سلبية املرىض وضع باستخدام قمنا التلوي للتحليل بالنسبة الكائنات هلذه النامذج لآلثار العشوائية لعوامل اخلطر ونتائج العدوى واالنحدار الفرعية قمنا بوضع خرائط النتشار لتحليل املجموعات التلوي املراقبة بيانات باستخدام ومنطقة دولة 20 يف اإلصابات هذه

املتاحة 40 بتضمني قمنا فحصها تم مقاال 6665 إمجايل من النتائج دراسة من 11 دولة ومنطقة يف التحليل التلوي شملت الدراسات

خطر ارتبط سلبية 2874 و إجيابية اختبار عينة 2411 املجمعة للبيتا املنتجة للبكترييا املوسع املمتد بالنطاق األعىل العدوى الكتاميز بالرعاية السابقة باملستشفيات وخاصة اإلقامة يف وحدة العناية املركزة (نسبة احتامل جممعة 65 بفاصل ثقة 95 304 إىل 137) التعرض للمضادات احليوية (وخاصة سيفالوسبورين من اجليل الثالث نسبة احتامل 48 بفاصل ثقة 95 225 إىل باملضادات العالج كان معا املتواجدة الرشوط بعض 1027) احليوية التجريبية واقيا من العدوى (نسبة احتامل 029 بفاصل ثقة 95 011 إىل 079) أقام املرىض املصابون لفرتات أطول يف املستشفى (26 يوما بفاصل ثقة 95 1281 إىل 3889) 95 ثقة 32 بفاصل احتامل (نسبة للوفاة أعىل وخماطر 182 إىل 580) كان انتشار العدوى بني السكان مرتفعا يف هذه

املناطق وكانت بيانات املراقبة اخلاصة باألطفال مفزعةاالستنتاج هناك حاجة إىل سياسات رعاية للمضادات احليوية ملنع اإلصابة وتشجيع العالج املناسب يف البلدان ومناطق جنوب رشق

آسيا وغرب املحيط اهلادي التابعة ملنظمة الصحة العاملية



protecteur vis-agrave-vis des infections (CR 029 IC agrave 95 de 011 agrave 079) Les patients infecteacutes se caracteacuterisaient par des seacutejours hospitaliers plus longs (26 jours IC agrave 95 de 1281 agrave 3889) et un risque de deacutecegraves plus eacuteleveacute (CR 32 IC agrave 95 de 182 agrave 580) La preacutevalence de lrsquoinfection dans la population eacutetait eacuteleveacutee dans ces reacutegions et les donneacutees de surveillance relatives aux enfants eacutetaient alarmantes

Conclusion Des politiques de gestion des antibiotiques pour preacutevenir les infections et encourager un traitement approprieacute sont neacutecessaires dans les pays et les reacutegions de lrsquoAsie du Sud-Est et du Pacifique occidental de lrsquoOMS

Резюме

Имеющиеся свидетельства устойчивости к антибиотикам у энтеробактерий продуцирующих бета-лактамазу расширенного спектра при лечении пациентов детского возраста в 20 странах и регионах системный обзор и метаанализЦель Выполнить системный обзор факторов риска исходов и распространенности инфекций вызванных микроорганизмами продуцирующими β-лактамазу расширенного спектра у пациентов детского и юношеского возраста в Юго-Восточной Азии и Западно-Тихоокеанском регионе (по классификации ВОЗ)Методы Авторы изучили сетевые базы данных на предмет статей датированных до июня 2018 года и посвященных исследованиям инфекций вызванных продуцирующими β-лактамазу энтеробактериями у пациентов в возрасте от 0 до 21 года В рассмотрение включались обсервационные межгрупповые когортные исследования и исследования типа laquoслучай-контрольraquo в которых сообщалось о пациентах с положительными и отрицательными результатами анализов на наличие указанных организмов Для метаанализа использовалось моделирование факторов риска и исходов инфекции со случайными эффектами Анализ подгрупп проводился с применением метарегрессии Была составлена карта распространенности таких инфекций в 20 странах и регионах с использованием имеющихся данных санитарного надзораРезультаты Из 6665 просмотренных статей в метаанализ были включены 40 исследований охватывающих 11 стран

и регионов В общей сложности исследования включали 2411 положительных и 2874 отрицательных образца Более высокий риск инфицирования бактериями вырабатывающими β-лактамазу расширенного спектра отмечался у пациентов ранее получавших лечение в больничных условиях особенно этот эффект был заметен для пациентов ОИТ (обобщенное ОШ 65 95-й ДИ от 304 до 1373) у тех кто принимал антибиотики (особенно цефалоспорины третьего поколения ОШ 48 95-й ДИ от 225 до 1027) и при некоторых сопутствующих заболеваниях Эмпирическое лечение антибиотиками имело защитный эффект в отношении инфекции (ОШ 029 95-й ДИ от 011 до 079) Инфицированные пациенты дольше оставались в больнице (26 дней 95-й ДИ от 1281 до 3889) и имели более высокий риск смерти (ОШ 32 95-й ДИ от 182 до 580) Частота инфекции в популяции указанных регионов была высокой а данные надзора среди детей mdash ужасающимиВывод В странах Юго-Восточной Азии и в Западно-Тихоокеанском регионе (по географической классификации ВОЗ) необходимо ввести политику ответственного назначения антибиотиков для предотвращения инфекции и поощрения правильного лечения

Resumen

Pruebas disponibles de la resistencia a los antibioacuteticos de las Enterobacteriaacuteceas productoras de betalactamasas de amplio espectro en pacientes pediaacutetricos de 20 paiacuteses y regiones una revisioacuten sistemaacutetica y un metanaacutelisisObjetivo Realizar una revisioacuten sistemaacutetica de los factores de riesgo los resultados y la prevalencia de la infeccioacuten de amplio espectro asociada a la betalactamasa en nintildeos y adultos joacutevenes en las regiones de Asia Sudoriental y el Paciacutefico Occidental de la Organizacioacuten Mundial de la Salud (OMS)Meacutetodos Hasta junio de 2018 se realizaron buacutesquedas en las bases de datos en liacutenea de estudios publicados sobre infeccioacuten con Enterobacteriaacuteceas productoras de betalactamasas de amplio espectro en individuos de 0 a 21 antildeos de edad Se incluyeron estudios de casos y controles de cohortes transversales y observacionales que reportaron pacientes positivos y negativos para estos organismos Para el metanaacutelisis se utilizoacute la modelizacioacuten de efectos aleatorios de los factores de riesgo y los resultados en cuanto a la infeccioacuten y la metarregresioacuten para el anaacutelisis de los subgrupos Mapeamos la prevalencia de estas infecciones en 20 paiacuteses y regiones utilizando los datos de vigilancia disponiblesResultados De los 6 665 artiacuteculos examinados se incluyeron 40 estudios de 11 paiacuteses y regiones en el metanaacutelisis Los estudios agrupados incluyeron 2 411 muestras positivas y 2 874 negativas Un mayor riesgo de infeccioacuten con bacterias productoras de betalactamasas de amplio espectro se asocioacute con la atencioacuten hospitalaria previa en particular las estancias en unidades de cuidados intensivos (OR agrupado 65 IC del 95 304 a 1373) la exposicioacuten a los antibioacuteticos (especialmente las cefalosporinas de tercera generacioacuten OR 48 IC del 95 225 a 1027)

y ciertas enfermedades coexistentes El tratamiento antibioacutetico empiacuterico fue protector contra la infeccioacuten (OR 029 IC del 95 011 a 079) Los pacientes infectados tuvieron estancias hospitalarias maacutes prolongadas (26 diacuteas IC del 95 1281 a 3889) y mayor riesgo de muerte (OR 32 IC del 95 182 a 580) La prevalencia de la infeccioacuten en la poblacioacuten era alta en estas regiones y los datos de vigilancia para los nintildeos eran alarmantesConclusioacuten Se necesitan poliacuteticas de gestioacuten de los antibioacuteticos para prevenir la infeccioacuten y fomentar el tratamiento adecuado en los paiacuteses y zonas de las regiones de Asia Sudoriental y el Paciacutefico Occidental de la OMS



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25 Jain A Mondal R Prevalence amp antimicrobial resistance pattern of extended spectrum beta-lactamase producing Klebsiella spp isolated from cases of neonatal septicaemia Indian J Med Res 2007 Jan125(1)89ndash94 PMID 17332661

26 Kuo KC Shen YH Hwang KP Clinical implications and risk factors of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infection in children a case-control retrospective study in a medical center in southern Taiwan J Microbiol Immunol Infect 2007 Jun40(3)248ndash54 PMID 17639166

27 Lee J Pai H Kim YK Kim NH Eun BW Kang HJ et al Control of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a childrenrsquos hospital by changing antimicrobial agent usage policy J Antimicrob Chemother 2007 Sep60629ndash37 doi httpdxdoiorg101093jacdkm225 PMID 17599919

28 Sehgal R Gaind R Chellani H Agarwal P Extended-spectrum beta lactamase-producing gram-negative bacteria clinical profile and outcome in a neonatal intensive care unit Ann Trop Paediatr 2007 Mar27(1)45ndash54 doi httpdxdoiorg101179146532807X170501 PMID 17469732

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30 Anandan S Thomas N Veeraraghavan B Jana AK Prevalence of extended- spectrum beta-lactamase producing Escherichia coli and Klebsiella spp in a neonatal intensive care unit Indian Pediatr 2009 Dec46(12)1106ndash7 PMID 20061592

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40 Themphachana M Kanobthammakul S Nakaguchi Y Singkhamanans K Yadrak P Sukhumungoon P Virulence characteristics and antimicrobial susceptibility of uropathogens from patients on Phuket Island Thailand Southeast Asian J Trop Med Public Health 2014 Sep45(5)1090ndash8 PMID 25417510

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42 Zuo MF Liu HL Zhu ML Shu QZ Jiang L [Pathologic bacterial distribution and antibiotic resistance in induced sputum of infants aged from 1 to 3 months with lower respiratory tract infection] Zhongguo Dang Dai Er Ke Za Zhi 2014 Dec16(12)1226ndash30 [Chinese] PMID 25523570

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45 Nisha KV Shenoy RD Shetty V Shenoy V Shetty A Comparative study on antibiotic resistance profile of extended-spectrum beta-lactamase and non-extended-spectrum beta-lactamase Escherichia coli infections among pediatric population with community-acquired urinary tract infections in a tertiary care centre Int J Sci Stud 20153(6)47ndash51

46 Agarwal G Kapil A Kabra SK Das BK Dwivedi SN Characterization of Pseudomonas aeruginosa isolated from chronically infected children with cystic fibrosis in India BMC Microbiol 2005 07 215(1)43 doi httpdxdoiorg1011861471-2180-5-43 PMID 16033658

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49 Tsai MH Lee IT Chu SM Lien R Huang HR Chiang MC et al Clinical and molecular characteristics of neonatal extended-spectrum β-lactamase-producing Gram-negative bacteremia a 12-year case-control-control study of a referral center in Taiwan PLoS One 2016 08 911(8)e0159744 doi httpdxdoiorg101371journalpone0159744 PMID 27505270

50 Chen KS Hu Y Guo X Guo F Antibiotic susceptibility patterns and beta-lactamase genotype of recent isolates of ESBL-producing Klebsiella pneumoniae in the intensive care unit of neonatology department Int J Infect Dis 2010 0714S20ndash20 doi httpdxdoiorg101016S1201-9712(10)60057-4

51 He X Xie M Li S Ye J Peng Q Ma Q et al Antimicrobial resistance in bacterial pathogens among hospitalized children with community acquired lower respiratory tract infections in Dongguan China (2011ndash2016) BMC Infect Dis 2017 09 1117(1)614 doi httpdxdoiorg101186s12879-017-2710-4 PMID 28893195

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54 Nisha KV Veena SA Rathika SD Vijaya SM Avinash SK Antimicrobial susceptibility risk factors and prevalence of bla cefotaximase temoneira and sulfhydryl variable genes among Escherichia coli in community-acquired pediatric urinary tract infection J Lab Physicians 2017 Jul-Sep9(3)156ndash62 doi httpdxdoiorg1041030974-2727208262 PMID 28706384

55 Tsai WL Hung CH Chen HA Wang JL Huang IF Chiou YH et al Extended-spectrum β-lactamase-producing Escherichia coli bacteremia Comparison of pediatric and adult populations J Microbiol Immunol Infect 2018 Dec51(6)723ndash31 doi httpdxdoiorg101016jjmii201708005 PMID 28927684

56 Bunjoungmanee P Tangsathapornpong A Kulalert P Clinical manifestations and risk factors in urinary tract infection caused by community-acquired extended-spectrum beta-lactamase enzyme producing bacteria in children Southeast Asian J Trop Med Public Health 201849(1)123ndash32

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58 Weerasinghe NP Vidanagama D Perera B Herath HMM De Silva Nagahawatte A Re-exploring the value of surveillance cultures in predicting pathogens of late onset neonatal sepsis in a tertiary care hospital in southern Sri Lanka BMC Res Notes 2018 05 2911(1)340 doi httpdxdoiorg101186s13104-018-3448-9 PMID 29843815

59 Hu YJ Ogyu A Cowling BJ Fukuda K Pang HH Available evidence of antibiotic resistance from extended-spectrum β-lactamase-producing Enterobacteriaceae in paediatric patients in 20 countries a systematic review and meta-analysisa quantitative analysis London Figshare 2019 doi httpdxdoiorg106084m9figshare8009873 doi httpdxdoiorg106084m9figshare8009873

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61 Ramos NL Dzung DT Stopsack K Jankoacute V Pourshafie MR Katouli M et al Characterisation of uropathogenic Escherichia coli from children with urinary tract infection in different countries Eur J Clin Microbiol Infect Dis 2011 Dec30(12)1587ndash93 doi httpdxdoiorg101007s10096-011-1264-4 PMID 21509475

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65 Fischer MM Bild M Hospital use of antibiotics as the main driver of infections with antibiotic-resistant bacteria ndash a reanalysis of recent data from the European Union bioRxiv 2019553537 Cold Spring Harbor Cold Spring Harbor Labaoratory 2019 doi httpdxdoiorghttpsdoiorg101101553537doi httpdxdoiorg101101553537

66 Honda H Ohmagari N Tokuda Y Mattar C Warren DKJCID Antimicrobial stewardship in inpatient settings in the Asia Pacific Region a systematic review and meta-analysis Clin Infect Dis 2017 May 1564 suppl_2S119ndash26 doi httpdxdoiorg101093cidcix017 PMID 28475777



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68 Zaoutis TE Goyal M Chu JH Coffin SE Bell LM Nachamkin I et al Risk factors for and outcomes of bloodstream infection caused by extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species in children Pediatrics 2005 Apr115(4)942ndash9 doi httpdxdoiorg101542peds2004-1289 PMID 15805368

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70 Topaloglu R Er I Dogan BG Bilginer Y Ozaltin F Besbas N et al Risk factors in community-acquired urinary tract infections caused by ESBL-producing bacteria in children Pediatr Nephrol 2010 May25(5)919ndash25 doi httpdxdoiorg101007s00467-009-1431-3 PMID 20151161

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73 Esposito S Gioia R De Simone G Noviello S Lombardi D Di Crescenzo VG et al Bacterial epidemiology and antimicrobial resistance in the surgery wards of a large teaching hospital in southern Italy Mediterr J Hematol Infect Dis 2015 06 17(1)e2015040 doi httpdxdoiorg104084mjhid2015040 PMID 26075047

74 Ccedilakmakccedili M Antibiotic stewardship programmes and the surgeonrsquos role J Hosp Infect 2015 Apr89(4)264ndash6 doi httpdxdoiorg101016jjhin201501006 PMID 25744279

75 Cusini A Rampini SK Bansal V Ledergerber B Kuster SP Ruef C et al Different patterns of inappropriate antimicrobial use in surgical and medical units at a tertiary care hospital in Switzerland a prevalence survey PLoS One 2010 11 165(11)e14011 doi httpdxdoiorg101371journalpone0014011 PMID 21103362

76 Auta A Hadi MA Oga E Adewuyi EO Abdu-Aguye SN Adeloye D et al Global access to antibiotics without prescription in community pharmacies a systematic review and meta-analysis J Infect 2019 Jan78(1)8ndash18 doi httpdxdoiorg101016jjinf201807001 PMID 29981773

77 Roberts RR Hota B Ahmad I Scott RD 2nd Foster SD Abbasi F et al Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital implications for antibiotic stewardship Clin Infect Dis 2009 Oct 1549(8)1175ndash84 doi httpdxdoiorg101086605630 PMID 19739972

78 Hijazi SM Fawzi MA Ali FM Abd El Galil KH Prevalence and characterization of extended-spectrum beta-lactamases producing Enterobacteriaceae in healthy children and associated risk factors Ann Clin Microbiol Antimicrob 2016 01 2915(1)3 doi httpdxdoiorg101186s12941-016-0121-9 PMID 26823288

79 Strysko JP Mony V Cleveland J Siddiqui H Homel P Gagliardo C International travel is a risk factor for extended-spectrum β-lactamase-producing Enterobacteriaceae acquisition in children a case-case-control study in an urban US hospital Travel Med Infect Dis 2016 Nov - Dec14(6)568ndash71 doi httpdxdoiorg101016jtmaid201611012 PMID 27890813

80 Taumlngdeacuten T Cars O Melhus A Loumlwdin E Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum β-lactamases a prospective study with Swedish volunteers Antimicrob Agents Chemother 2010 Sep54(9)3564ndash8 doi httpdxdoiorg101128AAC00220-10 PMID 20547788

81 Chaurasia S Sivanandan S Agarwal R Ellis S Sharland M Sankar MJ Neonatal sepsis in South Asia huge burden and spiralling antimicrobial resistance BMJ 2019 01 22364k5314 doi httpdxdoiorg101136bmjk5314 PMID 30670451

Bull World Health Organ 201997485ndash500B| doi httpdxdoiorg102471BLT18225698 A


(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash17

yea

rs14

249

9317

157

Esch

eric

hia

coli

Kleb

siella

pn

eum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Jain

et a

l 20

0321

Indi

a1

year

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

728

165

3679

400

E co

li K

pne

umon

iae

Ente

roba

cter

sp

pD

oubl

e di

sk sy

nerg

y te

stCL

SI 2

000

amp N

CCLS

dat

e N

SBo

o et

al

2005

22M

alay

sia19

96ndashO

ct 2

002

Case

ndashcon

trol

7 ye

ars

Hos

pita

lSe

psis

Vario

usN

eona

tes

350

8080

2236

9K

pne

umon

iae

Ente

roba

cter

spp

Dou

ble

disk

di

ffusio

nM

inist

ry o

f Hea

lth

of M

alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

ndashDec

20

01Co

hort

1 ye

arH

ospi

tal

Nos

ocom

ial

infe

ctio

nVa

rious

Neo

nate

s76

3442

4476

E co

li K

pne

umon

iae

KSD

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Hua

ng e

t al

2007

24Ch

ina

Jan

2000

ndashDec

20

02Co

hort

3 ye

ars

Hos

pita

lN

osoc

omia

l in

fect

ion

Vario

usN

eona

tes

3922

1756

2358

E co

li K

pne

umon

iae

Dou

ble

disk

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ffusio

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200

0

Jain

amp M

onda

l 200

725b

Indi

aJa

n 20

04ndashD

ec

2005

Coho

rt2

year

sH

ospi

tal

Seps

isBl

ood

Neo

nate

s10

058

4258

2995

K p

neum

onia

e En

tero

bact

er sp

pD

oubl

e di

sk

diffu

sion

NCC

LS 2

003

Kuo

et a

l 20

0726

Taiw

an C

hina

Jan

2000

ndashOct

20

05Ca

sendashc

ontro

l5

year

s 9

mon

ths

Hos

pita

lVa

rious

Vario

usBi

rth

to N

S10

854

5428

274

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Lee

et a

l 20

0727

Repu

blic

of

Kore

aJa

n 19

99ndashD

ec

2005

Coho

rt7

year

sH

ospi

tal

Vario

usVa

rious

NS

228

3554

2925

2E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

st V

itek-

GNI c

ard

CLSI

200

5

Sehg

al e

t al

2007

28In

dia

April

200

2ndashM

ay

2003

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

7538

2561

75M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Bhat

tach

arje

e et

al

2008

29b

Indi

a14

mon

ths

Coho

rt1

year

2

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

243

2658

3224

3M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

CLSI

200

8

Anan

dan

et a

l 20

0930

bIn

dia

Jan

2003

ndashDec

20

07Co

hort

5 ye

ars

Hos

pita

lSe

psis

Bloo

dN

eona

tes

9468

2672

8330

E co

li K

pne

umon

iae

Not

spec

ifyCL

SI 2

008

Kim

et a

l 20

0931

Repu

blic

of

Kore

aJa

n 20

04ndashA

pr

2009

Coho

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year

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ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

Child

ren

854

3283

1768

1E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

S

Shak

il et

al

2010

32In

dia

Jan

2006

ndashFeb

20

07Co

hort

1 ye

ars

Hos

pita

lVa

rious

Vario

usN

eona

tes

238

104

107

4446

9E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Gau

rav

et a

l 20

1133

Indi

aM

ay 2

007ndash

Apr

2008

Case

ndashcon

trol

1 ye

arH

ospi

tal

Seps

isBl

ood

Neo

nate

s34

450

5236

5116

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI d

ate

NS

Liu

et a

l 20

1134

Chin

aFe

b 20

09ndashJ

an

2011

Coho

rt2

year

sH

ospi

tal

Low

er re

spira

tory

tra

ct in

fect

ion

Sput

umlt

3 y

ears

242

9414

839

242

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

dat

e N

S

Wei

et a

l 20

1135

Chin

aJa

n 20

09ndashD

ec

2009

Obs

erva

tiona

l1

year

Hos

pita

lLo

wer

resp

irato

ry

tract

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ctio

nSp

utum

lt 1

yea

r27

214

412

853

1380

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

CLSI

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9

Min

ami e

t al

2012

36Ja

pan

July

201

1 (1

day

)Cr

oss-

sect

iona

l1

day

Hos

pita

lVa

rious

Rect

alle

12

year

s50

446

1262

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

200

8

Zhen

g et

al

2012

37Ch

ina

2002

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8Co

hort

6 ye

ars

Hos

pita

lH

aem

atol

ogic

al

mal

igna

ncy

Bloo

dlt

16

year

s10

919

3852

3264

E co

li K

pne

umon

iae

Vite

k 60

syst

emN

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dat

e N

S

Vija

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nthi

et a

l 20

1338

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aD

ec 2

009ndash

Nov

20

10Co

hort

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tal

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rious

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nate

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08

3917

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Mul

tiple

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iesa

Dou

ble

disk

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ffusio

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ate

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Fan

et a

l 201

439Ta

iwan

Chi

na20

02ndash2

006

Case

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trol

4 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

lt 1

5 ye

ars

312

104

208

3364

67E

coli

Dou

ble

disk

di

ffusio

nCL

SI 2

007

Them

phac

hana

et a

l 20

1440

Thai

land

Febndash

Sep

2013

Obs

erva

tiona

l8

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 2

1 ye

ars

166

8283

2616

6E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

2

Youn

g et

al

2014

41Si

ngap

ore

Nov

200

6ndashFe

b 20

07O

bser

vatio

nal

3 m

onth

sCo

mm

unity

Vario

usVa

rious

lt 2

1 ye

ars

1006

6912

44

1006

ESBL

-pro

duci

ng

Ente

roba

cter

iace

ae m

ethi

cilli

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taph

yloc

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s aur

eus

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omyc

in-re

sista

nt E

nter

ococ

cus

spp

Dou

ble

disk

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ffusio

nCL

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007

Zuo

et a

l 20

1442

Chin

aJa

nndashD

ec 2

013

Obs

erva

tiona

l1

year

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

1ndash3

mon

ths

622

9394

7937

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coli

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neum

onia

e Ki

rby-

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r disk

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ffusio

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012

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ng e

t al

2015

43Vi

et N

amJu

l 201

1ndashN

ov

2012

Coho

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year

4

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nVa

rious

3 m

onth

sndash15

ye

ars

216

2217

5214

3E

coli

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neum

onia

e D

oubl

e di

sk

diffu

sion

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7

Han

et a

l 20

1517

cRe

publ

ic o

f Ko

rea

Apr 2

009ndash

Mar

20

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hort

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ars

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ia

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ile)

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li K

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iae

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Han

et a

l 20

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publ

ic o

f Ko

rea

Jan

2010

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20

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hort

4 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 1

8 ye

ars

205

2218

910

211

E co

li K

pne

umon

iae

Vite

k 2

syst

emN

S


Bull World Health Organ 201997485ndash500B| doi httpdxdoiorg102471BLT18225698

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

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sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

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alen

ce

of ES

BL

infe

ctio

n

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f iso

late

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ectio

n m

etho

dGu

idel

ines

use

d

ESBL

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sitiv

eES

BL-

nega

tive

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a et

al

2015

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201

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n 20

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hort

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ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

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rine

le 1

8 ye

ars

385

159

226

4138

5E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

dat

e N

S

Agar

wal

et a

l 20

16 46

bIn

dia

2009

ndash201

2Co

hort

4 ye

ars

Hos

pita

lD

iarrh

oea

Stoo

lYo

ung

child

ren

6339

2398

1963

39E

coli

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neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

SAm

ornc

haic

haro

ensu

k 2

01647

Thai

land

Jan

2010

ndashDec

20

14Co

hort

5 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash15

yea

rs11

719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

CLSI

dat

e N

S

Shar

ma

et a

l 20

1648

Indi

aJa

n 20

13ndashA

ug

2014

Obs

erva

tiona

l1

year

7

mon

ths

Hos

pita

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psis

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tes

1449

101

6661

1449

Mul

tiple

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iesa

Dou

ble

disk

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rgy

test

NCC

LS d

ate

NS

Tsai

et a

l 20

1649

Taiw

an C

hina

Jan

2001

ndashDec

20

12Ca

sendashc

ontro

l12

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

350

7731

614

542

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

201

2

Chen

et a

l 20

1750

Taiw

an C

hina

Jan

2004

ndashJul

20

15Cr

oss-

sect

iona

l11

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

275

2219

27E

coli

Not

spec

ifyN

S

He

et a

l 20

1751

Chin

aM

ar 2

011ndash

Jun

2016

Coho

rt4

year

s 3

mon

ths

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

1 m

onth

ndash5 y

ears

236

6472

4723

60E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stCL

SI d

ate

NS

Kim

et a

l 20

1752

Repu

blic

of

Kore

aJa

n 20

10ndashJ

un

2015

Coho

rt5

year

s 5

mon

ths

Hos

pita

lBa

cter

aem

iaBl

ood

le 1

7 ye

ars

185

4993

3518

5E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stN

CCLS

200

1

Man

dal e

t al

2017

53In

dia

Two

cons

ecut

ive

year

Coho

rt2

year

sCo

mm

unity

Dia

rrhoe

aSt

ool

0ndash60

mon

ths

633

7211

938

633

E co

liM

odifi

ed K

irby-

Baue

r disk

diff

usio

nCL

SI d

ate

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Nish

a et

al

2017

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dia

Nov

201

2ndashM

ar

2016

Coho

rt4

year

s 5

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

3 m

onth

sndash18

ye

ars

523

196

327

3852

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coli

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y-Ba

uer d

isk

diffu

sion

CLSI

201

0

Tsai

et a

l 20

1755

Taiw

an C

hina

2010

ndash201

4O

bser

vatio

nal

5 ye

ars

Hos

pita

lBa

cter

aem

iaBl

ood

lt 3

yea

rs41

1427

3441

E co

liN

SN

SBu

njou

ngm

anee

et a

l 20

1856

Thai

land

Jun

2016

ndashMay

20

17Ca

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l1

year

Hos

pita

l amp

com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

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onth

ndash5 y

ears

8040

4023

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coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

0

Kita

gaw

a et

al

2018

57In

done

sia a

nd

Japa

nJa

nndashN

ov 2

014

Case

ndashcon

trol

1 ye

arH

ospi

tal amp

co

mm

unity

Urin

ary

tract

in

fect

ion

Urin

e0ndash

15 y

ears

9437

1339

94E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Wee

rasin

ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

1Co

hort

3 m

onth

sH

ospi

tal

Vario

usVa

rious

Neo

nate

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188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

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ffusio

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CD

C 2

011

CDC

Cen

ters

for D

iseas

e Co

ntro

l and

Pre

vent

ion

CLS

I Clin

ical

and

Lab

orat

ory

Stan

dard

s Ins

titut

e E

SBL

ext

ende

d-sp

ectru

m β

-lact

amas

e-pr

oduc

ing

bact

eria

NCC

LS N

atio

nal C

omm

ittee

for C

linic

al L

abor

ator

y St

anda

rds

NS

not

spec

ified

a M

ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

onas

spp

Acin

etob

acte

r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6



Search strategy

We made a comprehensive search without language limitation of online databases for articles published from 1 January 1940 to 30 June 2018 (Box 1) Two researchers independently con-ducted the search and screened the titles abstracts and full texts of the pa-pers We used a standardized piloted data collection form to determine whether papers were appropriate for inclusion The researchers applied the NewcastlendashOttawa scale to assess risk of bias in non-randomized stud-ies14 Studies scoring ge 5 and le 8 were designated low risk of bias ge 3 and le 4 as moderate and le 2 as high We incorporated the quality assessment results into our sensitivity analysis using the Meta-analyses Of Observa-tional Studies in Epidemiology check-list Discrepancies at any stage of the analysis were resolved by consensus of the researchers

Selection criteria

We included cohort casendashcontrol and observational or cross-sectional stud-ies We defined the target population as children aged from birth to 21 years according the American Academy of Paediatrics guidelines15 We included studies that were conducted in the WHO South-East Asia and Western Pacific Regions and that recorded both positive and negative results of testing for extended-spectrum β-lactamase-producing bacteria

Outcome measures

The principal outcome measure was patientsrsquo infection status defined by whether specimens obtained test-ed positive or negative for infection with extended-spectrum β-lactamase-producing bacteria We analysed infec-tion status by risk sub-groups medical history in the 3 months before the infection (hospital stay intensive care unit admission surgery) exposure to invasive life support antibiotic therapy and co-morbidities or underlying conditions Other outcomes recorded were hospital length of stay mortal-ity persistent bacteraemia antibiotic residence and duration of fever after antibiotic therapy

Data synthesis and analysis

For the meta-analysis we pooled the data on number of isolates (four studies) or patients with isolates (37 studies) us-ing a MantelndashHaenszel random-effects model to determine the risk of infection with extended-spectrum β-lactamase-producing bacteria16 We calculated pooled odds ratio (OR) and 95 con-fidence intervals (CI) for dichotomous outcomes and weighted mean difference and 95 CI for continuous outcomes All tests were two-tailed and P lt 005 was considered statistically significant If studies provided median and inter-quartile range we made estimates of the mean and standardized deviation (SD)17

We assessed the heterogeneity of the studies using the I2 statistic which eval-

uates the consistency of study results The cut-off for defining heterogeneity was I2 gt 5018 Our sensitivity analyses were based on sample size on the over-all summary estimates19 We evaluated whether this restricted analysis affected the magnitude direction and statistical significance of the overall summary estimate Additional sensitivity analy-ses assessed the different types of study designs settings and risk of bias

We carried out meta-regression to explore each potential factor contribut-ing to heterogeneity between studies such as study location design duration and setting and patientsrsquo age and diag-nosis for all included studies reporting mortality and persistent bacteraemia We used funnel plots with Egger re-gression test to assess publication bias (P lt 01)

All statistical analyses were per-formed with R software version 340 (R Foundation for Statistical Computing Vienna Austria) using the Meta and Metafor meta-analysis packages

Prevalence study

We obtained data on the prevalence of extended-spectrum β-lactamase-associated infection from the same studies included in the meta-analysis We also made a search for other data sources in the published and grey lit-erature (Box 1) We included data on children (ages 0ndash21 years) where avail-able and all age groups if data for these ages were unavailable We calculated percentage prevalence by the number of people or isolates testing positive for extended-spectrum β-lactamases out of the total population or isolates tested For casendashcontrol studies the overall prevalence rate was extracted instead Numbers of cases and samples were extracted if stated by the source Where population maps were provided in the source material the average of the range were extracted as the prevalence in the country We pooled the prevalence data by calculating the mean of the extracted data from all sources for each country

ResultsMeta-analysis

Study selection and characteristics

The database search yielded 6665 ar-ticles We removed 1089 duplicates and excluded a further 3046 studies after

Box 1 Search strategy used in the systemic review of extended-spectrum β-lactamase-associated infection among children and young adults in South-East Asia and Western Pacific countries

We searched online databases (Embasereg MEDLINEreg Cochrane Library Web of Science Scopus OvidSPreg EBSCO) electronic abstract databases and references in published articles For the prevalence study we also searched the grey literature including the websites of the World Health Organization and the United States Centers for Disease Control surveillance systems related to antimicrobial resistance dissertations conference reports and country reports When more information about studies was needed we contacted authors or website administrators

We used the following keywords

extended-spectrum beta-lactamase OR extended-spectrum beta-lactamase OR ESBL OR ESBLs OR ESBL-producing

AND paediatric OR pediatric OR juvenile OR child OR children OR adolescence OR infant OR neonat OR neonatal OR newborn OR nursery

AND Asia OR Asia Pacific OR South Asia OR The Western Pacific OR South-East Asia OR Australia OR Bangladesh OR Bhutan OR Brunei Darussalam OR Cambodia OR China OR Cook Islands OR Democratic Peoples Republic of Korea OR Fiji OR India OR Indonesia OR Japan OR Kiribati OR Lao Peoples Democratic Republic OR Malaysia OR Maldives OR Marshall Islands OR Federated States of Micronesia (Federated States of ) OR Mongolia OR Myanmar OR Nauru OR Nepal OR New Zealand OR Niue OR Palau OR Papua New Guinea OR Philippines OR Republic of Korea OR Samoa OR Singapore OR Solomon Islands OR Sri Lanka OR Thailand OR Timor-Leste OR Tonga OR Tuvalu OR Vanuatu OR VietNam





Risk factors





Treatment outcomes










negative infections













Validity tests








6 1258 124 399 65 859 646 (304 to 1373) 65


3 223 NA 110 NA 113 1142b (minus786 to 3071) 99


4 837 213 395 134 442 501 (350 to 719) 79


11 2149 355 808 328 1341 201 (167 to 243) 90


11 2318 384 777 249 1541 481 (225 to 1027) 89


4 703 84 238 132 465 182 (116 to 286) 0


13 2289 340 584 457 1705 358 (230 to 557) 60


5 803 102 192 463 611 029 (011 to 079) 65


5 805 216 283 350 522 377 (135 to 1056) 79


3 682 148 241 303 441 335 (054 to 2061) 91








Total no of

patients





clavulanic acid




3500 3400 19 2900 2200 69 01 600 (-1015ndash2215)



-10 5 0 5 10






01 02 05 1 2 5 20





Prevalence study









-20 0 20 40 60






01 02 05 1 2 5 100








ble

4

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ias i

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ded

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eta-

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ysis

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xten

ded-

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ciate

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g ch

ildre

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ts in

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ple

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rate

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istica

l tes

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et a

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o et

al

2007

260

11

00

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01

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arm

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ai e

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utco

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ps a

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rabl

e b

ased

on

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stud

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sign

or a

naly

sis

b Max

imum

scor

e 8

c C

ross

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tiona

l stu

dy

Not

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e ap

plie

d th

e N

ewca

stle

ndashOtta

wa

scal

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isk o

f bia

s in

non-

rand

omize

d st

udie

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nly

stud

ies s

corin

g ge

5 an

d le

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ere

desig

nate

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sk o

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Man

tel-H

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adom

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cts



Tabl

e 5

Ri

sk o

f bia

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coho

rt st

udie

s inc

lude

d in

the

met

a-an

alys

is of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n am

ong

child

ren

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g ad

ults

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uth-

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ific

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sed

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rt

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ctio

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non-

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sed

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rt

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rtai

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t of

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osur

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mon

stra

tion

that

ou

tcom

e of

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rest

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as n

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nt a

t the

st

art o

f stu

dy

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rts a

re

com

para

ble

base

d on

the

desig

n or

an

alys

is

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ent o

f ou

tcom

ea

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w -u

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ur

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co

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s

Kim

et a

l 20

0220

00

10

01

11

4Ja

in e

t al

2003

210

01

00

11

14

Chiu

et a

l 20

0523

10

10

01

11

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uang

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l 20

0724

00

10

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11

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in amp

Mon

dal 2

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00

10

01

11

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e et

al

2007

271

01

00

11

15

Sehg

al e

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2007

280

01

00

11

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tach

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2008

290

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dan

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l 20

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11

4Ki

m e

t al

2009

310

01

00

11

14

Shak

il et

al

2010

321

01

00

11

15

Liu

et a

l 20

1134

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10

01

11

4W

ei e

t al

2011

350

01

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11

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Zhen

g et

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2012

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00

11

14

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yaka

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l 20

1338

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ng e

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2015

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l 20

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04

a Sub

ject

s in

diffe

rent

out

com

e gr

oups

are

com

para

ble

bas

ed o

n th

e st

udy

desig

n or

ana

lysis

Con

foun

ding

fact

ors a

re c

ontro

lled

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imum

scor

e 8

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eutro

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ia st

udy

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tract

infe

ctio

n st

udy

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es W

e ap

plie

d th

e N

ewca

stle

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wa

scal

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isk o

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rand

omize

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udie

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nly

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corin

g ge

5 an

d le

8 w

ere

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nate

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sk o

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3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h











Pooled preva-lence

No of people

No () ESBL-positive

No of people

No () ESBL-positive


















Fig

6

Map

of p

reva

lenc

e of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s

087

517

503

500

kmN

Prev

alen

ce o

f ES

BL-a

ssoc

iate

d in

fect

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0-80

80ndash6

060

ndash40

40ndash2

020

ndash0N

o da

ta

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ts an

d ch

ildre

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ildre

n

ESBL

ext

ende

d-sp

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m β

-lact

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eN

otes

We

pool

ed d

ata

from

a se

arch

of t

he p

ublis

hed

and

grey

lite

ratu

re fo

r sur

veill

ance

dat

a fro

m a

ll M

embe

r Sta

tes a

nd a

reas

in th

e W

orld

Hea

lth O

rgan

izat

ion

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c Re

gion

s Th

e m

ap fo

r adu

lts a

nd c

hild

ren

incl

udes

dat

a fro

m A

ustra

lia B

huta

n B

rune

i Dar

ussa

lam

Cam

bodi

a Ta

iwan

Chi

na C

hina

Hon

g Ko

ng S

peci

al A

dmin

istra

tive

Regi

on I

ndia

Ind

ones

ia J

apan

Fed

erat

ed S

tate

s of M

icro

nesia

(Fed

erat

ed S

tate

s of)

Mya

nmar

Nep

al N

ew Z

eala

nd

Papu

a N

ew G

uine

a P

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pine

s Re

publ

ic o

f Kor

ea S

inga

pore

Tha

iland

and

Vie

t Nam

The

map

for c

hild

ren

only

(age

s 0ndash2

1 ye

ars)

incl

udes

dat

a fro

m A

ustra

lia (2

5

) Ch

ina

(54

3)

Taiw

an C

hina

(28

7)

Indi

a (4

59

) In

done

sia (3

90

) Ja

pan

(90

)

New

Zea

land

(28

)

Repu

blic

of K

orea

(23

7)

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apor

e (4

0

) Sr

i Lan

ka (3

60

) Th

aila

nd (2

17

) an

d Vi

et N

am (3

95

)



















Reacutesumeacute
















Резюме



Resumen





























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

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0ndash17

yea

rs14

249

9317

157

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238

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107

4446

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onia

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sk

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sion

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aM

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Case

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tal

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E co

li K

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Dou

ble

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Low

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ble

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aJa

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ami e

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rious

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tiple

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ble

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8

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al

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ina

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hort

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ars

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ct

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b 20

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20

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Hos

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ct

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li K

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ct

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20

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ct

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ctio

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li K

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orat

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ma

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ths

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ive

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Dou

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Cen

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vent

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CLS

I Clin

ical

and

Lab

orat

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Stan

dard

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titut

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SBL

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ende

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-lact

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eria

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atio

nal C

omm

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for C

linic

al L

abor

ator

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anda

rds

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not

spec

ified

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ultip

le sp

ecie

s inc

lude

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ebsie

lla p

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Esc

heric

hia

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Pseu

dom

onas

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Acin

etob

acte

r spp

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erob

acte

r spp

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obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6





Risk factors





Treatment outcomes










negative infections













Validity tests








6 1258 124 399 65 859 646 (304 to 1373) 65


3 223 NA 110 NA 113 1142b (minus786 to 3071) 99


4 837 213 395 134 442 501 (350 to 719) 79


11 2149 355 808 328 1341 201 (167 to 243) 90


11 2318 384 777 249 1541 481 (225 to 1027) 89


4 703 84 238 132 465 182 (116 to 286) 0


13 2289 340 584 457 1705 358 (230 to 557) 60


5 803 102 192 463 611 029 (011 to 079) 65


5 805 216 283 350 522 377 (135 to 1056) 79


3 682 148 241 303 441 335 (054 to 2061) 91








Total no of

patients





clavulanic acid




3500 3400 19 2900 2200 69 01 600 (-1015ndash2215)



-10 5 0 5 10






01 02 05 1 2 5 20





Prevalence study









-20 0 20 40 60






01 02 05 1 2 5 100








ble

4

Risk

of b

ias i

n ca

sendashc

ontr

ol a

nd cr

oss-

sect

iona

l stu

dies

inclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st

Asia

and

Wes

tern

Pac

ific c

ount

ries

2005

ndash201

8

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal s

core

b

Repr

esen

tativ

e-ne

ss o

f sam

ple

Sam

ple

size

Non-

resp

on-

dent

sAs

cert

ainm

ent

of e

xpos

ure

(risk

fa

ctor

)

Diffe

rent

out

com

e gr

oups

are

com

pa-

rabl

e co

nfou

ndin

g fa

ctor

s are

cont

rolle

da

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ssm

ent o

f ex

posu

re o

r ou

tcom

e

Sam

e m

etho

d of

as

cert

ainm

ent f

or

case

s and

cont

rols

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resp

onse

rate

or

stat

istica

l tes

t

Boo

et a

l 20

0522

01

11

01

11

6Ku

o et

al

2007

260

11

00

11

15

Gau

rav

et a

l 20

1133

01

10

01

11

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inam

i et a

l 20

1236

c1

00

00

11

14

Fan

et a

l 201

4390

11

10

11

16

Them

phac

hana

et a

l 20

1440

c0

10

00

11

14

Youn

g et

al

2014

41c

11

01

01

10

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o et

al

2014

42c

00

10

11

01

4Sh

arm

a et

al

2016

48c

01

01

01

11

5Ts

ai e

t al

2017

551

10

10

11

16

Chen

et a

l 20

1750

11

00

01

11

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njou

ngm

anee

et a

l 20

1856

01

10

01

10

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taga

wa

et a

l 20

1857

01

10

01

10

4a S

ubje

cts i

n di

ffere

nt o

utco

me

grou

ps a

re c

ompa

rabl

e b

ased

on

the

stud

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sign

or a

naly

sis

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imum

scor

e 8

c C

ross

-sec

tiona

l stu

dy

Not

es W

e ap

plie

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e N

ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h W

e m

ade

Man

tel-H

aens

zel r

adom

-effe

cts



Tabl

e 5

Ri

sk o

f bia

s in

coho

rt st

udie

s inc

lude

d in

the

met

a-an

alys

is of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n am

ong

child

ren

and

youn

g ad

ults

in So

uth-

East

Asia

and

Wes

tern

Pac

ific

coun

trie

s 20

02ndash2

018

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal

scor

eb

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esen

tativ

enes

s of

the

expo

sed

coho

rt

Sele

ctio

n of

the

non-

expo

sed

coho

rt

Asce

rtai

nmen

t of

exp

osur

eDe

mon

stra

tion

that

ou

tcom

e of

inte

rest

w

as n

ot p

rese

nt a

t the

st

art o

f stu

dy

Coho

rts a

re

com

para

ble

base

d on

the

desig

n or

an

alys

is

Asse

ssm

ent o

f ou

tcom

ea

Follo

w -u

p lo

ng

enou

gh fo

r ou

tcom

es to

occ

ur

Adeq

uacy

of

follo

w-u

p of

co

hort

s

Kim

et a

l 20

0220

00

10

01

11

4Ja

in e

t al

2003

210

01

00

11

14

Chiu

et a

l 20

0523

10

10

01

11

5H

uang

et a

l 20

0724

00

10

01

11

4Ja

in amp

Mon

dal 2

00725

00

10

01

11

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e et

al

2007

271

01

00

11

15

Sehg

al e

t al

2007

280

01

00

11

14

Bhat

tach

arje

e et

al

2008

290

01

00

11

14

Anan

dan

et a

l 20

0930

00

10

01

11

4Ki

m e

t al

2009

310

01

00

11

14

Shak

il et

al

2010

321

01

00

11

15

Liu

et a

l 20

1134

00

10

01

11

4W

ei e

t al

2011

350

01

00

11

14

Zhen

g et

al

2012

370

01

00

11

14

Vija

yaka

nthi

et a

l 20

1338

00

10

01

11

5Th

emph

acha

na e

t al

2014

400

01

00

11

14

Duo

ng e

t al

2015

430

01

00

11

14

Han

et a

l 20

1517

c0

01

00

11

14

Han

et a

l 20

1544

d0

01

00

11

14

Nish

a et

al

2015

450

01

01

11

15

Agar

wal

et a

l 20

16 46

0

01

00

11

14

Amor

ncha

icha

roen

suk

20

1647

00

10

11

11

5

He

et a

l 20

1751

10

10

01

11

5Ki

m e

t al

2017

521

01

00

11

15

Man

dal e

t al

2017

530

01

01

11

04

Nish

a et

al

2017

540

01

00

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Fig

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Tabl

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Ch

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Stud

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Shar

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Repu

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185

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2017

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Two

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2017

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Nov

201

2ndashM

ar

2016

Coho

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Com

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ood

lt 3

yea

rs41

1427

3441

E co

liN

SN

SBu

njou

ngm

anee

et a

l 20

1856

Thai

land

Jun

2016

ndashMay

20

17Ca

sendashc

ontro

l1

year

Hos

pita

l amp

com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

1 m

onth

ndash5 y

ears

8040

4023

80E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

0

Kita

gaw

a et

al

2018

57In

done

sia a

nd

Japa

nJa

nndashN

ov 2

014

Case

ndashcon

trol

1 ye

arH

ospi

tal amp

co

mm

unity

Urin

ary

tract

in

fect

ion

Urin

e0ndash

15 y

ears

9437

1339

94E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Wee

rasin

ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

1Co

hort

3 m

onth

sH

ospi

tal

Vario

usVa

rious

Neo

nate

s50

188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI amp

CD

C 2

011

CDC

Cen

ters

for D

iseas

e Co

ntro

l and

Pre

vent

ion

CLS

I Clin

ical

and

Lab

orat

ory

Stan

dard

s Ins

titut

e E

SBL

ext

ende

d-sp

ectru

m β

-lact

amas

e-pr

oduc

ing

bact

eria

NCC

LS N

atio

nal C

omm

ittee

for C

linic

al L

abor

ator

y St

anda

rds

NS

not

spec

ified

a M

ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

onas

spp

Acin

etob

acte

r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6







Validity tests








6 1258 124 399 65 859 646 (304 to 1373) 65


3 223 NA 110 NA 113 1142b (minus786 to 3071) 99


4 837 213 395 134 442 501 (350 to 719) 79


11 2149 355 808 328 1341 201 (167 to 243) 90


11 2318 384 777 249 1541 481 (225 to 1027) 89


4 703 84 238 132 465 182 (116 to 286) 0


13 2289 340 584 457 1705 358 (230 to 557) 60


5 803 102 192 463 611 029 (011 to 079) 65


5 805 216 283 350 522 377 (135 to 1056) 79


3 682 148 241 303 441 335 (054 to 2061) 91








Total no of

patients





clavulanic acid




3500 3400 19 2900 2200 69 01 600 (-1015ndash2215)



-10 5 0 5 10






01 02 05 1 2 5 20





Prevalence study









-20 0 20 40 60






01 02 05 1 2 5 100








ble

4

Risk

of b

ias i

n ca

sendashc

ontr

ol a

nd cr

oss-

sect

iona

l stu

dies

inclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st

Asia

and

Wes

tern

Pac

ific c

ount

ries

2005

ndash201

8

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal s

core

b

Repr

esen

tativ

e-ne

ss o

f sam

ple

Sam

ple

size

Non-

resp

on-

dent

sAs

cert

ainm

ent

of e

xpos

ure

(risk

fa

ctor

)

Diffe

rent

out

com

e gr

oups

are

com

pa-

rabl

e co

nfou

ndin

g fa

ctor

s are

cont

rolle

da

Asse

ssm

ent o

f ex

posu

re o

r ou

tcom

e

Sam

e m

etho

d of

as

cert

ainm

ent f

or

case

s and

cont

rols

Non-

resp

onse

rate

or

stat

istica

l tes

t

Boo

et a

l 20

0522

01

11

01

11

6Ku

o et

al

2007

260

11

00

11

15

Gau

rav

et a

l 20

1133

01

10

01

11

5M

inam

i et a

l 20

1236

c1

00

00

11

14

Fan

et a

l 201

4390

11

10

11

16

Them

phac

hana

et a

l 20

1440

c0

10

00

11

14

Youn

g et

al

2014

41c

11

01

01

10

5Zu

o et

al

2014

42c

00

10

11

01

4Sh

arm

a et

al

2016

48c

01

01

01

11

5Ts

ai e

t al

2017

551

10

10

11

16

Chen

et a

l 20

1750

11

00

01

11

5Bu

njou

ngm

anee

et a

l 20

1856

01

10

01

10

4Ki

taga

wa

et a

l 20

1857

01

10

01

10

4a S

ubje

cts i

n di

ffere

nt o

utco

me

grou

ps a

re c

ompa

rabl

e b

ased

on

the

stud

y de

sign

or a

naly

sis

b Max

imum

scor

e 8

c C

ross

-sec

tiona

l stu

dy

Not

es W

e ap

plie

d th

e N

ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h W

e m

ade

Man

tel-H

aens

zel r

adom

-effe

cts



Tabl

e 5

Ri

sk o

f bia

s in

coho

rt st

udie

s inc

lude

d in

the

met

a-an

alys

is of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n am

ong

child

ren

and

youn

g ad

ults

in So

uth-

East

Asia

and

Wes

tern

Pac

ific

coun

trie

s 20

02ndash2

018

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal

scor

eb

Repr

esen

tativ

enes

s of

the

expo

sed

coho

rt

Sele

ctio

n of

the

non-

expo

sed

coho

rt

Asce

rtai

nmen

t of

exp

osur

eDe

mon

stra

tion

that

ou

tcom

e of

inte

rest

w

as n

ot p

rese

nt a

t the

st

art o

f stu

dy

Coho

rts a

re

com

para

ble

base

d on

the

desig

n or

an

alys

is

Asse

ssm

ent o

f ou

tcom

ea

Follo

w -u

p lo

ng

enou

gh fo

r ou

tcom

es to

occ

ur

Adeq

uacy

of

follo

w-u

p of

co

hort

s

Kim

et a

l 20

0220

00

10

01

11

4Ja

in e

t al

2003

210

01

00

11

14

Chiu

et a

l 20

0523

10

10

01

11

5H

uang

et a

l 20

0724

00

10

01

11

4Ja

in amp

Mon

dal 2

00725

00

10

01

11

4Le

e et

al

2007

271

01

00

11

15

Sehg

al e

t al

2007

280

01

00

11

14

Bhat

tach

arje

e et

al

2008

290

01

00

11

14

Anan

dan

et a

l 20

0930

00

10

01

11

4Ki

m e

t al

2009

310

01

00

11

14

Shak

il et

al

2010

321

01

00

11

15

Liu

et a

l 20

1134

00

10

01

11

4W

ei e

t al

2011

350

01

00

11

14

Zhen

g et

al

2012

370

01

00

11

14

Vija

yaka

nthi

et a

l 20

1338

00

10

01

11

5Th

emph

acha

na e

t al

2014

400

01

00

11

14

Duo

ng e

t al

2015

430

01

00

11

14

Han

et a

l 20

1517

c0

01

00

11

14

Han

et a

l 20

1544

d0

01

00

11

14

Nish

a et

al

2015

450

01

01

11

15

Agar

wal

et a

l 20

16 46

0

01

00

11

14

Amor

ncha

icha

roen

suk

20

1647

00

10

11

11

5

He

et a

l 20

1751

10

10

01

11

5Ki

m e

t al

2017

521

01

00

11

15

Man

dal e

t al

2017

530

01

01

11

04

Nish

a et

al

2017

540

01

00

11

14

Tsai

et a

l 20

1755

10

00

01

11

4W

eera

singh

e et

al

2018

580

11

00

11

04

a Sub

ject

s in

diffe

rent

out

com

e gr

oups

are

com

para

ble

bas

ed o

n th

e st

udy

desig

n or

ana

lysis

Con

foun

ding

fact

ors a

re c

ontro

lled

b Max

imum

scor

e 8

C N

eutro

poen

ia st

udy

d Urin

ary

tract

infe

ctio

n st

udy

Not

es W

e ap

plie

d th

e N

ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h











Pooled preva-lence

No of people

No () ESBL-positive

No of people

No () ESBL-positive


















Fig

6

Map

of p

reva

lenc

e of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s

087

517

503

500

kmN

Prev

alen

ce o

f ES

BL-a

ssoc

iate

d in

fect

ion

10

0-80

80ndash6

060

ndash40

40ndash2

020

ndash0N

o da

ta

Adul

ts an

d ch

ildre

nCh

ildre

n

ESBL

ext

ende

d-sp

ectru

m β

-lact

amas

eN

otes

We

pool

ed d

ata

from

a se

arch

of t

he p

ublis

hed

and

grey

lite

ratu

re fo

r sur

veill

ance

dat

a fro

m a

ll M

embe

r Sta

tes a

nd a

reas

in th

e W

orld

Hea

lth O

rgan

izat

ion

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c Re

gion

s Th

e m

ap fo

r adu

lts a

nd c

hild

ren

incl

udes

dat

a fro

m A

ustra

lia B

huta

n B

rune

i Dar

ussa

lam

Cam

bodi

a Ta

iwan

Chi

na C

hina

Hon

g Ko

ng S

peci

al A

dmin

istra

tive

Regi

on I

ndia

Ind

ones

ia J

apan

Fed

erat

ed S

tate

s of M

icro

nesia

(Fed

erat

ed S

tate

s of)

Mya

nmar

Nep

al N

ew Z

eala

nd

Papu

a N

ew G

uine

a P

hilip

pine

s Re

publ

ic o

f Kor

ea S

inga

pore

Tha

iland

and

Vie

t Nam

The

map

for c

hild

ren

only

(age

s 0ndash2

1 ye

ars)

incl

udes

dat

a fro

m A

ustra

lia (2

5

) Ch

ina

(54

3)

Taiw

an C

hina

(28

7)

Indi

a (4

59

) In

done

sia (3

90

) Ja

pan

(90

)

New

Zea

land

(28

)

Repu

blic

of K

orea

(23

7)

Sing

apor

e (4

0

) Sr

i Lan

ka (3

60

) Th

aila

nd (2

17

) an

d Vi

et N

am (3

95

)



















Reacutesumeacute
















Резюме



Resumen





























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash17

yea

rs14

249

9317

157

Esch

eric

hia

coli

Kleb

siella

pn

eum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Jain

et a

l 20

0321

Indi

a1

year

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

728

165

3679

400

E co

li K

pne

umon

iae

Ente

roba

cter

sp

pD

oubl

e di

sk sy

nerg

y te

stCL

SI 2

000

amp N

CCLS

dat

e N

SBo

o et

al

2005

22M

alay

sia19

96ndashO

ct 2

002

Case

ndashcon

trol

7 ye

ars

Hos

pita

lSe

psis

Vario

usN

eona

tes

350

8080

2236

9K

pne

umon

iae

Ente

roba

cter

spp

Dou

ble

disk

di

ffusio

nM

inist

ry o

f Hea

lth

of M

alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

ndashDec

20

01Co

hort

1 ye

arH

ospi

tal

Nos

ocom

ial

infe

ctio

nVa

rious

Neo

nate

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3442

4476

E co

li K

pne

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iae

KSD

oubl

e di

sk

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sion

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Hua

ng e

t al

2007

24Ch

ina

Jan

2000

ndashDec

20

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hort

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ars

Hos

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lN

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omia

l in

fect

ion

Vario

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2358

E co

li K

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iae

Dou

ble

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Jain

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onda

l 200

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n 20

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ec

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tal

Seps

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ood

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058

4258

2995

K p

neum

onia

e En

tero

bact

er sp

pD

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sk

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Kuo

et a

l 20

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Taiw

an C

hina

Jan

2000

ndashOct

20

05Ca

sendashc

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l5

year

s 9

mon

ths

Hos

pita

lVa

rious

Vario

usBi

rth

to N

S10

854

5428

274

K p

neum

onia

e D

oubl

e di

sk

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sion

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LS 2

001

Lee

et a

l 20

0727

Repu

blic

of

Kore

aJa

n 19

99ndashD

ec

2005

Coho

rt7

year

sH

ospi

tal

Vario

usVa

rious

NS

228

3554

2925

2E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

st V

itek-

GNI c

ard

CLSI

200

5

Sehg

al e

t al

2007

28In

dia

April

200

2ndashM

ay

2003

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

7538

2561

75M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Bhat

tach

arje

e et

al

2008

29b

Indi

a14

mon

ths

Coho

rt1

year

2

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

243

2658

3224

3M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

CLSI

200

8

Anan

dan

et a

l 20

0930

bIn

dia

Jan

2003

ndashDec

20

07Co

hort

5 ye

ars

Hos

pita

lSe

psis

Bloo

dN

eona

tes

9468

2672

8330

E co

li K

pne

umon

iae

Not

spec

ifyCL

SI 2

008

Kim

et a

l 20

0931

Repu

blic

of

Kore

aJa

n 20

04ndashA

pr

2009

Coho

rt5

year

s 2

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

Child

ren

854

3283

1768

1E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

S

Shak

il et

al

2010

32In

dia

Jan

2006

ndashFeb

20

07Co

hort

1 ye

ars

Hos

pita

lVa

rious

Vario

usN

eona

tes

238

104

107

4446

9E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Gau

rav

et a

l 20

1133

Indi

aM

ay 2

007ndash

Apr

2008

Case

ndashcon

trol

1 ye

arH

ospi

tal

Seps

isBl

ood

Neo

nate

s34

450

5236

5116

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI d

ate

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tal

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tiple

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ble

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e N

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aJa

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tiple

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ble

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20

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ct

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ctio

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li K

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ma

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linic

al L

abor

ator

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anda

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spec

ified

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ultip

le sp

ecie

s inc

lude

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ebsie

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onia

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heric

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onas

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r spp

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erob

acte

r spp

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obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

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on

patie

nts a

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es

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nia

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yd U

rinar

y tra

ct in

fect

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stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6





Total no of

patients





clavulanic acid




3500 3400 19 2900 2200 69 01 600 (-1015ndash2215)



-10 5 0 5 10






01 02 05 1 2 5 20





Prevalence study









-20 0 20 40 60






01 02 05 1 2 5 100








ble

4

Risk

of b

ias i

n ca

sendashc

ontr

ol a

nd cr

oss-

sect

iona

l stu

dies

inclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st

Asia

and

Wes

tern

Pac

ific c

ount

ries

2005

ndash201

8

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal s

core

b

Repr

esen

tativ

e-ne

ss o

f sam

ple

Sam

ple

size

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resp

on-

dent

sAs

cert

ainm

ent

of e

xpos

ure

(risk

fa

ctor

)

Diffe

rent

out

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e gr

oups

are

com

pa-

rabl

e co

nfou

ndin

g fa

ctor

s are

cont

rolle

da

Asse

ssm

ent o

f ex

posu

re o

r ou

tcom

e

Sam

e m

etho

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as

cert

ainm

ent f

or

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cont

rols

Non-

resp

onse

rate

or

stat

istica

l tes

t

Boo

et a

l 20

0522

01

11

01

11

6Ku

o et

al

2007

260

11

00

11

15

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rav

et a

l 20

1133

01

10

01

11

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inam

i et a

l 20

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c1

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00

11

14

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l 201

4390

11

10

11

16

Them

phac

hana

et a

l 20

1440

c0

10

00

11

14

Youn

g et

al

2014

41c

11

01

01

10

5Zu

o et

al

2014

42c

00

10

11

01

4Sh

arm

a et

al

2016

48c

01

01

01

11

5Ts

ai e

t al

2017

551

10

10

11

16

Chen

et a

l 20

1750

11

00

01

11

5Bu

njou

ngm

anee

et a

l 20

1856

01

10

01

10

4Ki

taga

wa

et a

l 20

1857

01

10

01

10

4a S

ubje

cts i

n di

ffere

nt o

utco

me

grou

ps a

re c

ompa

rabl

e b

ased

on

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stud

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sign

or a

naly

sis

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imum

scor

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ross

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tiona

l stu

dy

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es W

e ap

plie

d th

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ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h W

e m

ade

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tel-H

aens

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adom

-effe

cts



Tabl

e 5

Ri

sk o

f bia

s in

coho

rt st

udie

s inc

lude

d in

the

met

a-an

alys

is of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n am

ong

child

ren

and

youn

g ad

ults

in So

uth-

East

Asia

and

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tern

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ific

coun

trie

s 20

02ndash2

018

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orSe

lect

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para

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tal

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tativ

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expo

sed

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rt

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ctio

n of

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non-

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rtai

nmen

t of

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osur

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mon

stra

tion

that

ou

tcom

e of

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rest

w

as n

ot p

rese

nt a

t the

st

art o

f stu

dy

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rts a

re

com

para

ble

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d on

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desig

n or

an

alys

is

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ent o

f ou

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ea

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p lo

ng

enou

gh fo

r ou

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es to

occ

ur

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uacy

of

follo

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p of

co

hort

s

Kim

et a

l 20

0220

00

10

01

11

4Ja

in e

t al

2003

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01

00

11

14

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et a

l 20

0523

10

10

01

11

5H

uang

et a

l 20

0724

00

10

01

11

4Ja

in amp

Mon

dal 2

00725

00

10

01

11

4Le

e et

al

2007

271

01

00

11

15

Sehg

al e

t al

2007

280

01

00

11

14

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tach

arje

e et

al

2008

290

01

00

11

14

Anan

dan

et a

l 20

0930

00

10

01

11

4Ki

m e

t al

2009

310

01

00

11

14

Shak

il et

al

2010

321

01

00

11

15

Liu

et a

l 20

1134

00

10

01

11

4W

ei e

t al

2011

350

01

00

11

14

Zhen

g et

al

2012

370

01

00

11

14

Vija

yaka

nthi

et a

l 20

1338

00

10

01

11

5Th

emph

acha

na e

t al

2014

400

01

00

11

14

Duo

ng e

t al

2015

430

01

00

11

14

Han

et a

l 20

1517

c0

01

00

11

14

Han

et a

l 20

1544

d0

01

00

11

14

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a et

al

2015

450

01

01

11

15

Agar

wal

et a

l 20

16 46

0

01

00

11

14

Amor

ncha

icha

roen

suk

20

1647

00

10

11

11

5

He

et a

l 20

1751

10

10

01

11

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m e

t al

2017

521

01

00

11

15

Man

dal e

t al

2017

530

01

01

11

04

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a et

al

2017

540

01

00

11

14

Tsai

et a

l 20

1755

10

00

01

11

4W

eera

singh

e et

al

2018

580

11

00

11

04

a Sub

ject

s in

diffe

rent

out

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e gr

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com

para

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ed o

n th

e st

udy

desig

n or

ana

lysis

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foun

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fact

ors a

re c

ontro

lled

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imum

scor

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ia st

udy

d Urin

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mod

erat

e an

d le

2 as

hig

h











Pooled preva-lence

No of people

No () ESBL-positive

No of people

No () ESBL-positive


















Fig

6

Map

of p

reva

lenc

e of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s

087

517

503

500

kmN

Prev

alen

ce o

f ES

BL-a

ssoc

iate

d in

fect

ion

10

0-80

80ndash6

060

ndash40

40ndash2

020

ndash0N

o da

ta

Adul

ts an

d ch

ildre

nCh

ildre

n

ESBL

ext

ende

d-sp

ectru

m β

-lact

amas

eN

otes

We

pool

ed d

ata

from

a se

arch

of t

he p

ublis

hed

and

grey

lite

ratu

re fo

r sur

veill

ance

dat

a fro

m a

ll M

embe

r Sta

tes a

nd a

reas

in th

e W

orld

Hea

lth O

rgan

izat

ion

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c Re

gion

s Th

e m

ap fo

r adu

lts a

nd c

hild

ren

incl

udes

dat

a fro

m A

ustra

lia B

huta

n B

rune

i Dar

ussa

lam

Cam

bodi

a Ta

iwan

Chi

na C

hina

Hon

g Ko

ng S

peci

al A

dmin

istra

tive

Regi

on I

ndia

Ind

ones

ia J

apan

Fed

erat

ed S

tate

s of M

icro

nesia

(Fed

erat

ed S

tate

s of)

Mya

nmar

Nep

al N

ew Z

eala

nd

Papu

a N

ew G

uine

a P

hilip

pine

s Re

publ

ic o

f Kor

ea S

inga

pore

Tha

iland

and

Vie

t Nam

The

map

for c

hild

ren

only

(age

s 0ndash2

1 ye

ars)

incl

udes

dat

a fro

m A

ustra

lia (2

5

) Ch

ina

(54

3)

Taiw

an C

hina

(28

7)

Indi

a (4

59

) In

done

sia (3

90

) Ja

pan

(90

)

New

Zea

land

(28

)

Repu

blic

of K

orea

(23

7)

Sing

apor

e (4

0

) Sr

i Lan

ka (3

60

) Th

aila

nd (2

17

) an

d Vi

et N

am (3

95

)



















Reacutesumeacute
















Резюме



Resumen





























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

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nclu

ded

in th

e m

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anal

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Auth

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Stud

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ting

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nosis

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mpl

e ag

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of

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ren

No o

f sam

ples

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alen

ce

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late

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19

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Esch

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E co

li K

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Ente

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nerg

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SI 2

000

amp N

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dat

e N

SBo

o et

al

2005

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alay

sia19

96ndashO

ct 2

002

Case

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trol

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ars

Hos

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Vario

usN

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350

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pne

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Ente

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spp

Dou

ble

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inist

ry o

f Hea

lth

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alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

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20

01Co

hort

1 ye

arH

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tal

Nos

ocom

ial

infe

ctio

nVa

rious

Neo

nate

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li K

pne

umon

iae

KSD

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sion

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ng e

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2007

24Ch

ina

Jan

2000

ndashDec

20

02Co

hort

3 ye

ars

Hos

pita

lN

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omia

l in

fect

ion

Vario

usN

eona

tes

3922

1756

2358

E co

li K

pne

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iae

Dou

ble

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0

Jain

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onda

l 200

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Indi

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ec

2005

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Seps

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ood

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4258

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K p

neum

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tero

bact

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pD

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sk

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Kuo

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l 20

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Taiw

an C

hina

Jan

2000

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20

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mon

ths

Hos

pita

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rious

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Lee

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l 20

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Repu

blic

of

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ec

2005

Coho

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rious

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228

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2925

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coli

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onia

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nerg

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st V

itek-

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ard

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5

Sehg

al e

t al

2007

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dia

April

200

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ay

2003

Coho

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year

Hos

pita

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Bloo

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7538

2561

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ultip

le sp

ecie

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e di

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sion

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tach

arje

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al

2008

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Indi

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ths

Coho

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2

mon

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Hos

pita

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psis

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243

2658

3224

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saD

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sk

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sion

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8

Anan

dan

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l 20

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dia

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Hos

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Repu

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2010

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dia

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2006

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20

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Hos

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rious

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l 20

1133

Indi

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Apr

2008

Case

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trol

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tal

Seps

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ood

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nate

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E co

li K

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Dou

ble

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Low

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Sput

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ears

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9414

839

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Mul

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Dou

ble

disk

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dat

e N

S

Wei

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l 20

1135

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aJa

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ec

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Obs

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tiona

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Hos

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Dou

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ami e

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pan

July

201

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day

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iona

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Hos

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rious

Rect

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Mul

tiple

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8

Zhen

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al

2012

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ina

2002

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hort

6 ye

ars

Hos

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Nov

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Mul

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Dou

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Fan

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Chi

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Com

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Dou

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Sep

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Obs

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tiona

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Hos

pita

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ct

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ctio

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lt 2

1 ye

ars

166

8283

2616

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sk

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sion

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al

2014

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Nov

200

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b 20

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bser

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2015

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l 201

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ov

2012

Coho

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year

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Hos

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rious

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216

2217

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sk

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Han

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ic o

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Jan

2010

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ars

Hos

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205

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Auth

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rea

Stud

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nSt

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y set

ting

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nosis

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eSa

mpl

e ag

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child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

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eria

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det

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etho

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idel

ines

use

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sitiv

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BL-

nega

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Nish

a et

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2015

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dia

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201

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Com

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rinar

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ct

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ctio

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385

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isk

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dat

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S

Agar

wal

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l 20

16 46

bIn

dia

2009

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hort

4 ye

ars

Hos

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lD

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tek

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stem

CLSI

dat

e N

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haic

haro

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k 2

01647

Thai

land

Jan

2010

ndashDec

20

14Co

hort

5 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

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rine

0ndash15

yea

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719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

CLSI

dat

e N

S

Shar

ma

et a

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Indi

aJa

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ug

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Obs

erva

tiona

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Hos

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psis

Bloo

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1449

101

6661

1449

Mul

tiple

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iesa

Dou

ble

disk

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LS d

ate

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Tsai

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1649

Taiw

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hina

Jan

2001

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20

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sendashc

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l12

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

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350

7731

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Mul

tiple

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Dou

ble

disk

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201

2

Chen

et a

l 20

1750

Taiw

an C

hina

Jan

2004

ndashJul

20

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oss-

sect

iona

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yea

rsH

ospi

tal

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Bloo

dN

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275

2219

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Not

spec

ifyN

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He

et a

l 20

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Chin

aM

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Jun

2016

Coho

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year

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mon

ths

Hos

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ry

tract

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ears

236

6472

4723

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coli

K p

neum

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e D

oubl

e di

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nerg

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SI d

ate

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Kim

et a

l 20

1752

Repu

blic

of

Kore

aJa

n 20

10ndashJ

un

2015

Coho

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year

s 5

mon

ths

Hos

pita

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aem

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le 1

7 ye

ars

185

4993

3518

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coli

K p

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e D

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sk sy

nerg

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200

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Man

dal e

t al

2017

53In

dia

Two

cons

ecut

ive

year

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year

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Dia

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ths

633

7211

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633

E co

liM

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ate

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al

2017

54In

dia

Nov

201

2ndashM

ar

2016

Coho

rt4

year

s 5

mon

ths

Com

mun

ityU

rinar

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ct

infe

ctio

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ye

ars

523

196

327

3852

3E

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isk

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sion

CLSI

201

0

Tsai

et a

l 20

1755

Taiw

an C

hina

2010

ndash201

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bser

vatio

nal

5 ye

ars

Hos

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cter

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1427

3441

E co

liN

SN

SBu

njou

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anee

et a

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1856

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Jun

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Hos

pita

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com

mun

ityU

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ct

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ctio

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rine

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4023

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K p

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onia

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oubl

e di

sk

diffu

sion

CLSI

201

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Kita

gaw

a et

al

2018

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done

sia a

nd

Japa

nJa

nndashN

ov 2

014

Case

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tal amp

co

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unity

Urin

ary

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fect

ion

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e0ndash

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ears

9437

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e di

sk

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sion

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e N

S

Wee

rasin

ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

1Co

hort

3 m

onth

sH

ospi

tal

Vario

usVa

rious

Neo

nate

s50

188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI amp

CD

C 2

011

CDC

Cen

ters

for D

iseas

e Co

ntro

l and

Pre

vent

ion

CLS

I Clin

ical

and

Lab

orat

ory

Stan

dard

s Ins

titut

e E

SBL

ext

ende

d-sp

ectru

m β

-lact

amas

e-pr

oduc

ing

bact

eria

NCC

LS N

atio

nal C

omm

ittee

for C

linic

al L

abor

ator

y St

anda

rds

NS

not

spec

ified

a M

ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

onas

spp

Acin

etob

acte

r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6




Prevalence study









-20 0 20 40 60






01 02 05 1 2 5 100








ble

4

Risk

of b

ias i

n ca

sendashc

ontr

ol a

nd cr

oss-

sect

iona

l stu

dies

inclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st

Asia

and

Wes

tern

Pac

ific c

ount

ries

2005

ndash201

8

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal s

core

b

Repr

esen

tativ

e-ne

ss o

f sam

ple

Sam

ple

size

Non-

resp

on-

dent

sAs

cert

ainm

ent

of e

xpos

ure

(risk

fa

ctor

)

Diffe

rent

out

com

e gr

oups

are

com

pa-

rabl

e co

nfou

ndin

g fa

ctor

s are

cont

rolle

da

Asse

ssm

ent o

f ex

posu

re o

r ou

tcom

e

Sam

e m

etho

d of

as

cert

ainm

ent f

or

case

s and

cont

rols

Non-

resp

onse

rate

or

stat

istica

l tes

t

Boo

et a

l 20

0522

01

11

01

11

6Ku

o et

al

2007

260

11

00

11

15

Gau

rav

et a

l 20

1133

01

10

01

11

5M

inam

i et a

l 20

1236

c1

00

00

11

14

Fan

et a

l 201

4390

11

10

11

16

Them

phac

hana

et a

l 20

1440

c0

10

00

11

14

Youn

g et

al

2014

41c

11

01

01

10

5Zu

o et

al

2014

42c

00

10

11

01

4Sh

arm

a et

al

2016

48c

01

01

01

11

5Ts

ai e

t al

2017

551

10

10

11

16

Chen

et a

l 20

1750

11

00

01

11

5Bu

njou

ngm

anee

et a

l 20

1856

01

10

01

10

4Ki

taga

wa

et a

l 20

1857

01

10

01

10

4a S

ubje

cts i

n di

ffere

nt o

utco

me

grou

ps a

re c

ompa

rabl

e b

ased

on

the

stud

y de

sign

or a

naly

sis

b Max

imum

scor

e 8

c C

ross

-sec

tiona

l stu

dy

Not

es W

e ap

plie

d th

e N

ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h W

e m

ade

Man

tel-H

aens

zel r

adom

-effe

cts



Tabl

e 5

Ri

sk o

f bia

s in

coho

rt st

udie

s inc

lude

d in

the

met

a-an

alys

is of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n am

ong

child

ren

and

youn

g ad

ults

in So

uth-

East

Asia

and

Wes

tern

Pac

ific

coun

trie

s 20

02ndash2

018

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal

scor

eb

Repr

esen

tativ

enes

s of

the

expo

sed

coho

rt

Sele

ctio

n of

the

non-

expo

sed

coho

rt

Asce

rtai

nmen

t of

exp

osur

eDe

mon

stra

tion

that

ou

tcom

e of

inte

rest

w

as n

ot p

rese

nt a

t the

st

art o

f stu

dy

Coho

rts a

re

com

para

ble

base

d on

the

desig

n or

an

alys

is

Asse

ssm

ent o

f ou

tcom

ea

Follo

w -u

p lo

ng

enou

gh fo

r ou

tcom

es to

occ

ur

Adeq

uacy

of

follo

w-u

p of

co

hort

s

Kim

et a

l 20

0220

00

10

01

11

4Ja

in e

t al

2003

210

01

00

11

14

Chiu

et a

l 20

0523

10

10

01

11

5H

uang

et a

l 20

0724

00

10

01

11

4Ja

in amp

Mon

dal 2

00725

00

10

01

11

4Le

e et

al

2007

271

01

00

11

15

Sehg

al e

t al

2007

280

01

00

11

14

Bhat

tach

arje

e et

al

2008

290

01

00

11

14

Anan

dan

et a

l 20

0930

00

10

01

11

4Ki

m e

t al

2009

310

01

00

11

14

Shak

il et

al

2010

321

01

00

11

15

Liu

et a

l 20

1134

00

10

01

11

4W

ei e

t al

2011

350

01

00

11

14

Zhen

g et

al

2012

370

01

00

11

14

Vija

yaka

nthi

et a

l 20

1338

00

10

01

11

5Th

emph

acha

na e

t al

2014

400

01

00

11

14

Duo

ng e

t al

2015

430

01

00

11

14

Han

et a

l 20

1517

c0

01

00

11

14

Han

et a

l 20

1544

d0

01

00

11

14

Nish

a et

al

2015

450

01

01

11

15

Agar

wal

et a

l 20

16 46

0

01

00

11

14

Amor

ncha

icha

roen

suk

20

1647

00

10

11

11

5

He

et a

l 20

1751

10

10

01

11

5Ki

m e

t al

2017

521

01

00

11

15

Man

dal e

t al

2017

530

01

01

11

04

Nish

a et

al

2017

540

01

00

11

14

Tsai

et a

l 20

1755

10

00

01

11

4W

eera

singh

e et

al

2018

580

11

00

11

04

a Sub

ject

s in

diffe

rent

out

com

e gr

oups

are

com

para

ble

bas

ed o

n th

e st

udy

desig

n or

ana

lysis

Con

foun

ding

fact

ors a

re c

ontro

lled

b Max

imum

scor

e 8

C N

eutro

poen

ia st

udy

d Urin

ary

tract

infe

ctio

n st

udy

Not

es W

e ap

plie

d th

e N

ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h











Pooled preva-lence

No of people

No () ESBL-positive

No of people

No () ESBL-positive


















Fig

6

Map

of p

reva

lenc

e of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s

087

517

503

500

kmN

Prev

alen

ce o

f ES

BL-a

ssoc

iate

d in

fect

ion

10

0-80

80ndash6

060

ndash40

40ndash2

020

ndash0N

o da

ta

Adul

ts an

d ch

ildre

nCh

ildre

n

ESBL

ext

ende

d-sp

ectru

m β

-lact

amas

eN

otes

We

pool

ed d

ata

from

a se

arch

of t

he p

ublis

hed

and

grey

lite

ratu

re fo

r sur

veill

ance

dat

a fro

m a

ll M

embe

r Sta

tes a

nd a

reas

in th

e W

orld

Hea

lth O

rgan

izat

ion

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c Re

gion

s Th

e m

ap fo

r adu

lts a

nd c

hild

ren

incl

udes

dat

a fro

m A

ustra

lia B

huta

n B

rune

i Dar

ussa

lam

Cam

bodi

a Ta

iwan

Chi

na C

hina

Hon

g Ko

ng S

peci

al A

dmin

istra

tive

Regi

on I

ndia

Ind

ones

ia J

apan

Fed

erat

ed S

tate

s of M

icro

nesia

(Fed

erat

ed S

tate

s of)

Mya

nmar

Nep

al N

ew Z

eala

nd

Papu

a N

ew G

uine

a P

hilip

pine

s Re

publ

ic o

f Kor

ea S

inga

pore

Tha

iland

and

Vie

t Nam

The

map

for c

hild

ren

only

(age

s 0ndash2

1 ye

ars)

incl

udes

dat

a fro

m A

ustra

lia (2

5

) Ch

ina

(54

3)

Taiw

an C

hina

(28

7)

Indi

a (4

59

) In

done

sia (3

90

) Ja

pan

(90

)

New

Zea

land

(28

)

Repu

blic

of K

orea

(23

7)

Sing

apor

e (4

0

) Sr

i Lan

ka (3

60

) Th

aila

nd (2

17

) an

d Vi

et N

am (3

95

)



















Reacutesumeacute
















Резюме



Resumen





























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash17

yea

rs14

249

9317

157

Esch

eric

hia

coli

Kleb

siella

pn

eum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Jain

et a

l 20

0321

Indi

a1

year

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

728

165

3679

400

E co

li K

pne

umon

iae

Ente

roba

cter

sp

pD

oubl

e di

sk sy

nerg

y te

stCL

SI 2

000

amp N

CCLS

dat

e N

SBo

o et

al

2005

22M

alay

sia19

96ndashO

ct 2

002

Case

ndashcon

trol

7 ye

ars

Hos

pita

lSe

psis

Vario

usN

eona

tes

350

8080

2236

9K

pne

umon

iae

Ente

roba

cter

spp

Dou

ble

disk

di

ffusio

nM

inist

ry o

f Hea

lth

of M

alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

ndashDec

20

01Co

hort

1 ye

arH

ospi

tal

Nos

ocom

ial

infe

ctio

nVa

rious

Neo

nate

s76

3442

4476

E co

li K

pne

umon

iae

KSD

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Hua

ng e

t al

2007

24Ch

ina

Jan

2000

ndashDec

20

02Co

hort

3 ye

ars

Hos

pita

lN

osoc

omia

l in

fect

ion

Vario

usN

eona

tes

3922

1756

2358

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nN

CCLS

200

0

Jain

amp M

onda

l 200

725b

Indi

aJa

n 20

04ndashD

ec

2005

Coho

rt2

year

sH

ospi

tal

Seps

isBl

ood

Neo

nate

s10

058

4258

2995

K p

neum

onia

e En

tero

bact

er sp

pD

oubl

e di

sk

diffu

sion

NCC

LS 2

003

Kuo

et a

l 20

0726

Taiw

an C

hina

Jan

2000

ndashOct

20

05Ca

sendashc

ontro

l5

year

s 9

mon

ths

Hos

pita

lVa

rious

Vario

usBi

rth

to N

S10

854

5428

274

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Lee

et a

l 20

0727

Repu

blic

of

Kore

aJa

n 19

99ndashD

ec

2005

Coho

rt7

year

sH

ospi

tal

Vario

usVa

rious

NS

228

3554

2925

2E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

st V

itek-

GNI c

ard

CLSI

200

5

Sehg

al e

t al

2007

28In

dia

April

200

2ndashM

ay

2003

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

7538

2561

75M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Bhat

tach

arje

e et

al

2008

29b

Indi

a14

mon

ths

Coho

rt1

year

2

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

243

2658

3224

3M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

CLSI

200

8

Anan

dan

et a

l 20

0930

bIn

dia

Jan

2003

ndashDec

20

07Co

hort

5 ye

ars

Hos

pita

lSe

psis

Bloo

dN

eona

tes

9468

2672

8330

E co

li K

pne

umon

iae

Not

spec

ifyCL

SI 2

008

Kim

et a

l 20

0931

Repu

blic

of

Kore

aJa

n 20

04ndashA

pr

2009

Coho

rt5

year

s 2

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

Child

ren

854

3283

1768

1E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

S

Shak

il et

al

2010

32In

dia

Jan

2006

ndashFeb

20

07Co

hort

1 ye

ars

Hos

pita

lVa

rious

Vario

usN

eona

tes

238

104

107

4446

9E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Gau

rav

et a

l 20

1133

Indi

aM

ay 2

007ndash

Apr

2008

Case

ndashcon

trol

1 ye

arH

ospi

tal

Seps

isBl

ood

Neo

nate

s34

450

5236

5116

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI d

ate

NS

Liu

et a

l 20

1134

Chin

aFe

b 20

09ndashJ

an

2011

Coho

rt2

year

sH

ospi

tal

Low

er re

spira

tory

tra

ct in

fect

ion

Sput

umlt

3 y

ears

242

9414

839

242

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

dat

e N

S

Wei

et a

l 20

1135

Chin

aJa

n 20

09ndashD

ec

2009

Obs

erva

tiona

l1

year

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

lt 1

yea

r27

214

412

853

1380

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

200

9

Min

ami e

t al

2012

36Ja

pan

July

201

1 (1

day

)Cr

oss-

sect

iona

l1

day

Hos

pita

lVa

rious

Rect

alle

12

year

s50

446

1262

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

200

8

Zhen

g et

al

2012

37Ch

ina

2002

ndash200

8Co

hort

6 ye

ars

Hos

pita

lH

aem

atol

ogic

al

mal

igna

ncy

Bloo

dlt

16

year

s10

919

3852

3264

E co

li K

pne

umon

iae

Vite

k 60

syst

emN

CCLS

dat

e N

S

Vija

yaka

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l 20

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aD

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Nov

20

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tal

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tiple

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Dou

ble

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ffusio

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ars

Com

mun

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ct

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Dou

ble

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ths

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pita

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rinar

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ct

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ctio

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rine

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ars

166

8283

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coli

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onia

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e di

sk

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sion

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g et

al

2014

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200

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b 20

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bser

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nal

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rious

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ths

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amJu

l 201

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ov

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ct

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ctio

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rious

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ars

216

2217

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neum

onia

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e di

sk

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sion

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7

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et a

l 20

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ic o

f Ko

rea

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20

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ia

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et a

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ic o

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rea

Jan

2010

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20

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hort

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ars

Hos

pita

lU

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ct

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ctio

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rine

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ars

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li K

pne

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rea

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y dat

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y set

ting

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nosis

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imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

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alen

ce

of ES

BL

infe

ctio

n

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f iso

late

s or

cultu

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eria

l spe

cies

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det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

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sitiv

eES

BL-

nega

tive

Nish

a et

al

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dia

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201

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n 20

15Co

hort

3 ye

ars

Com

mun

ityU

rinar

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ct

infe

ctio

nU

rine

le 1

8 ye

ars

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226

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coli

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sion

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dat

e N

S

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wal

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l 20

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dia

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2Co

hort

4 ye

ars

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pita

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iarrh

oea

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lYo

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tek

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stem

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haic

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k 2

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land

Jan

2010

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20

14Co

hort

5 ye

ars

Hos

pita

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y tra

ct

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ctio

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E co

li K

pne

umon

iae

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pita

l lab

orat

ory

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dat

e N

S

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ma

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l 20

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aJa

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ug

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ths

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psis

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tiple

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ble

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rgy

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ate

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an C

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mia

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tiple

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ble

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an C

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tal

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l 20

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aM

ar 2

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mon

ths

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onia

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e di

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nerg

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stCL

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ate

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Kim

et a

l 20

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ars

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nerg

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1

Man

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cons

ecut

ive

year

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liM

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201

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ar

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mun

ityU

rinar

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ct

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ctio

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sion

CLSI

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0

Tsai

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1755

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bser

vatio

nal

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ars

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liN

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njou

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ctio

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sion

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sion

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ded

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nia

stud

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ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6







ble

4

Risk

of b

ias i

n ca

sendashc

ontr

ol a

nd cr

oss-

sect

iona

l stu

dies

inclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st

Asia

and

Wes

tern

Pac

ific c

ount

ries

2005

ndash201

8

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal s

core

b

Repr

esen

tativ

e-ne

ss o

f sam

ple

Sam

ple

size

Non-

resp

on-

dent

sAs

cert

ainm

ent

of e

xpos

ure

(risk

fa

ctor

)

Diffe

rent

out

com

e gr

oups

are

com

pa-

rabl

e co

nfou

ndin

g fa

ctor

s are

cont

rolle

da

Asse

ssm

ent o

f ex

posu

re o

r ou

tcom

e

Sam

e m

etho

d of

as

cert

ainm

ent f

or

case

s and

cont

rols

Non-

resp

onse

rate

or

stat

istica

l tes

t

Boo

et a

l 20

0522

01

11

01

11

6Ku

o et

al

2007

260

11

00

11

15

Gau

rav

et a

l 20

1133

01

10

01

11

5M

inam

i et a

l 20

1236

c1

00

00

11

14

Fan

et a

l 201

4390

11

10

11

16

Them

phac

hana

et a

l 20

1440

c0

10

00

11

14

Youn

g et

al

2014

41c

11

01

01

10

5Zu

o et

al

2014

42c

00

10

11

01

4Sh

arm

a et

al

2016

48c

01

01

01

11

5Ts

ai e

t al

2017

551

10

10

11

16

Chen

et a

l 20

1750

11

00

01

11

5Bu

njou

ngm

anee

et a

l 20

1856

01

10

01

10

4Ki

taga

wa

et a

l 20

1857

01

10

01

10

4a S

ubje

cts i

n di

ffere

nt o

utco

me

grou

ps a

re c

ompa

rabl

e b

ased

on

the

stud

y de

sign

or a

naly

sis

b Max

imum

scor

e 8

c C

ross

-sec

tiona

l stu

dy

Not

es W

e ap

plie

d th

e N

ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h W

e m

ade

Man

tel-H

aens

zel r

adom

-effe

cts



Tabl

e 5

Ri

sk o

f bia

s in

coho

rt st

udie

s inc

lude

d in

the

met

a-an

alys

is of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n am

ong

child

ren

and

youn

g ad

ults

in So

uth-

East

Asia

and

Wes

tern

Pac

ific

coun

trie

s 20

02ndash2

018

Auth

orSe

lect

ion

Com

para

bilit

yEx

posu

reTo

tal

scor

eb

Repr

esen

tativ

enes

s of

the

expo

sed

coho

rt

Sele

ctio

n of

the

non-

expo

sed

coho

rt

Asce

rtai

nmen

t of

exp

osur

eDe

mon

stra

tion

that

ou

tcom

e of

inte

rest

w

as n

ot p

rese

nt a

t the

st

art o

f stu

dy

Coho

rts a

re

com

para

ble

base

d on

the

desig

n or

an

alys

is

Asse

ssm

ent o

f ou

tcom

ea

Follo

w -u

p lo

ng

enou

gh fo

r ou

tcom

es to

occ

ur

Adeq

uacy

of

follo

w-u

p of

co

hort

s

Kim

et a

l 20

0220

00

10

01

11

4Ja

in e

t al

2003

210

01

00

11

14

Chiu

et a

l 20

0523

10

10

01

11

5H

uang

et a

l 20

0724

00

10

01

11

4Ja

in amp

Mon

dal 2

00725

00

10

01

11

4Le

e et

al

2007

271

01

00

11

15

Sehg

al e

t al

2007

280

01

00

11

14

Bhat

tach

arje

e et

al

2008

290

01

00

11

14

Anan

dan

et a

l 20

0930

00

10

01

11

4Ki

m e

t al

2009

310

01

00

11

14

Shak

il et

al

2010

321

01

00

11

15

Liu

et a

l 20

1134

00

10

01

11

4W

ei e

t al

2011

350

01

00

11

14

Zhen

g et

al

2012

370

01

00

11

14

Vija

yaka

nthi

et a

l 20

1338

00

10

01

11

5Th

emph

acha

na e

t al

2014

400

01

00

11

14

Duo

ng e

t al

2015

430

01

00

11

14

Han

et a

l 20

1517

c0

01

00

11

14

Han

et a

l 20

1544

d0

01

00

11

14

Nish

a et

al

2015

450

01

01

11

15

Agar

wal

et a

l 20

16 46

0

01

00

11

14

Amor

ncha

icha

roen

suk

20

1647

00

10

11

11

5

He

et a

l 20

1751

10

10

01

11

5Ki

m e

t al

2017

521

01

00

11

15

Man

dal e

t al

2017

530

01

01

11

04

Nish

a et

al

2017

540

01

00

11

14

Tsai

et a

l 20

1755

10

00

01

11

4W

eera

singh

e et

al

2018

580

11

00

11

04

a Sub

ject

s in

diffe

rent

out

com

e gr

oups

are

com

para

ble

bas

ed o

n th

e st

udy

desig

n or

ana

lysis

Con

foun

ding

fact

ors a

re c

ontro

lled

b Max

imum

scor

e 8

C N

eutro

poen

ia st

udy

d Urin

ary

tract

infe

ctio

n st

udy

Not

es W

e ap

plie

d th

e N

ewca

stle

ndashOtta

wa

scal

e to

ass

ess r

isk o

f bia

s in

non-

rand

omize

d st

udie

s14 O

nly

stud

ies s

corin

g ge

5 an

d le

8 w

ere

desig

nate

d lo

w ri

sk o

f bia

s ge

3 an

d le

4 as

mod

erat

e an

d le

2 as

hig

h











Pooled preva-lence

No of people

No () ESBL-positive

No of people

No () ESBL-positive


















Fig

6

Map

of p

reva

lenc

e of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s

087

517

503

500

kmN

Prev

alen

ce o

f ES

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ssoc

iate

d in

fect

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10

0-80

80ndash6

060

ndash40

40ndash2

020

ndash0N

o da

ta

Adul

ts an

d ch

ildre

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ildre

n

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otes

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pool

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ata

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r sur

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ll M

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e W

orld

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lth O

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m A

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n B

rune

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lam

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a Ta

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na C

hina

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ng S

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on I

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Ind

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ia J

apan

Fed

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al N

ew Z

eala

nd

Papu

a N

ew G

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hilip

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publ

ic o

f Kor

ea S

inga

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Tha

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The

map

for c

hild

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only

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s 0ndash2

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incl

udes

dat

a fro

m A

ustra

lia (2

5

) Ch

ina

(54

3)

Taiw

an C

hina

(28

7)

Indi

a (4

59

) In

done

sia (3

90

) Ja

pan

(90

)

New

Zea

land

(28

)

Repu

blic

of K

orea

(23

7)

Sing

apor

e (4

0

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i Lan

ka (3

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aila

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d Vi

et N

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95

)



















Reacutesumeacute
















Резюме



Resumen





























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

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eria

l spe

cies

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ectio

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idel

ines

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d

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sitiv

eES

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nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

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yea

rs14

249

9317

157

Esch

eric

hia

coli

Kleb

siella

pn

eum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Jain

et a

l 20

0321

Indi

a1

year

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

728

165

3679

400

E co

li K

pne

umon

iae

Ente

roba

cter

sp

pD

oubl

e di

sk sy

nerg

y te

stCL

SI 2

000

amp N

CCLS

dat

e N

SBo

o et

al

2005

22M

alay

sia19

96ndashO

ct 2

002

Case

ndashcon

trol

7 ye

ars

Hos

pita

lSe

psis

Vario

usN

eona

tes

350

8080

2236

9K

pne

umon

iae

Ente

roba

cter

spp

Dou

ble

disk

di

ffusio

nM

inist

ry o

f Hea

lth

of M

alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

ndashDec

20

01Co

hort

1 ye

arH

ospi

tal

Nos

ocom

ial

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ctio

nVa

rious

Neo

nate

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4476

E co

li K

pne

umon

iae

KSD

oubl

e di

sk

diffu

sion

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LS 2

001

Hua

ng e

t al

2007

24Ch

ina

Jan

2000

ndashDec

20

02Co

hort

3 ye

ars

Hos

pita

lN

osoc

omia

l in

fect

ion

Vario

usN

eona

tes

3922

1756

2358

E co

li K

pne

umon

iae

Dou

ble

disk

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ffusio

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0

Jain

amp M

onda

l 200

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Indi

aJa

n 20

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ec

2005

Coho

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year

sH

ospi

tal

Seps

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ood

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nate

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058

4258

2995

K p

neum

onia

e En

tero

bact

er sp

pD

oubl

e di

sk

diffu

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NCC

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003

Kuo

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l 20

0726

Taiw

an C

hina

Jan

2000

ndashOct

20

05Ca

sendashc

ontro

l5

year

s 9

mon

ths

Hos

pita

lVa

rious

Vario

usBi

rth

to N

S10

854

5428

274

K p

neum

onia

e D

oubl

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sk

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sion

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Lee

et a

l 20

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Repu

blic

of

Kore

aJa

n 19

99ndashD

ec

2005

Coho

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year

sH

ospi

tal

Vario

usVa

rious

NS

228

3554

2925

2E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

st V

itek-

GNI c

ard

CLSI

200

5

Sehg

al e

t al

2007

28In

dia

April

200

2ndashM

ay

2003

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

7538

2561

75M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

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LS 2

002

Bhat

tach

arje

e et

al

2008

29b

Indi

a14

mon

ths

Coho

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year

2

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

243

2658

3224

3M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

CLSI

200

8

Anan

dan

et a

l 20

0930

bIn

dia

Jan

2003

ndashDec

20

07Co

hort

5 ye

ars

Hos

pita

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Bloo

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9468

2672

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E co

li K

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Not

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l 20

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Repu

blic

of

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n 20

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pr

2009

Coho

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ths

Com

mun

ityU

rinar

y tra

ct

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ctio

nU

rine

Child

ren

854

3283

1768

1E

coli

K p

neum

onia

e Vi

tek

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stem

CLSI

dat

e N

S

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il et

al

2010

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dia

Jan

2006

ndashFeb

20

07Co

hort

1 ye

ars

Hos

pita

lVa

rious

Vario

usN

eona

tes

238

104

107

4446

9E

coli

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neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Gau

rav

et a

l 20

1133

Indi

aM

ay 2

007ndash

Apr

2008

Case

ndashcon

trol

1 ye

arH

ospi

tal

Seps

isBl

ood

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nate

s34

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5236

5116

E co

li K

pne

umon

iae

Dou

ble

disk

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ffusio

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l 20

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aFe

b 20

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an

2011

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tal

Low

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spira

tory

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ct in

fect

ion

Sput

umlt

3 y

ears

242

9414

839

242

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

dat

e N

S

Wei

et a

l 20

1135

Chin

aJa

n 20

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ec

2009

Obs

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tiona

l1

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Hos

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ry

tract

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ctio

nSp

utum

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214

412

853

1380

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

CLSI

200

9

Min

ami e

t al

2012

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pan

July

201

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day

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oss-

sect

iona

l1

day

Hos

pita

lVa

rious

Rect

alle

12

year

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446

1262

Mul

tiple

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iesa

Dou

ble

disk

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rgy

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CLSI

200

8

Zhen

g et

al

2012

37Ch

ina

2002

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8Co

hort

6 ye

ars

Hos

pita

lH

aem

atol

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al

mal

igna

ncy

Bloo

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year

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E co

li K

pne

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k 60

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dat

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S

Vija

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et a

l 20

1338

Indi

aD

ec 2

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Nov

20

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hort

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tal

Seps

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rious

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Mul

tiple

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Dou

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ate

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Fan

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Chi

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ars

Com

mun

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ct

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ctio

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rine

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ars

312

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Dou

ble

disk

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ffusio

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Them

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l 20

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land

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Obs

erva

tiona

l8

mon

ths

Hos

pita

lU

rinar

y tra

ct

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ctio

nU

rine

lt 2

1 ye

ars

166

8283

2616

6E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

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2

Youn

g et

al

2014

41Si

ngap

ore

Nov

200

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b 20

07O

bser

vatio

nal

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onth

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mm

unity

Vario

usVa

rious

lt 2

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ars

1006

6912

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aJa

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Obs

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tiona

l1

year

Hos

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wer

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irato

ry

tract

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ctio

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utum

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ths

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coli

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r disk

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ng e

t al

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et N

amJu

l 201

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ov

2012

Coho

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year

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mon

ths

Hos

pita

lU

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ct

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ctio

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rious

3 m

onth

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ye

ars

216

2217

5214

3E

coli

K p

neum

onia

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oubl

e di

sk

diffu

sion

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7

Han

et a

l 20

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publ

ic o

f Ko

rea

Apr 2

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20

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li K

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k 2

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Han

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publ

ic o

f Ko

rea

Jan

2010

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20

14Co

hort

4 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 1

8 ye

ars

205

2218

910

211

E co

li K

pne

umon

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Vite

k 2

syst

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S



Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

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sitiv

eES

BL-

nega

tive

Nish

a et

al

2015

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dia

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201

2ndashJa

n 20

15Co

hort

3 ye

ars

Com

mun

ityU

rinar

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ct

infe

ctio

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ars

385

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226

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coli

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y-Ba

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isk

diffu

sion

CLSI

dat

e N

S

Agar

wal

et a

l 20

16 46

bIn

dia

2009

ndash201

2Co

hort

4 ye

ars

Hos

pita

lD

iarrh

oea

Stoo

lYo

ung

child

ren

6339

2398

1963

39E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

SAm

ornc

haic

haro

ensu

k 2

01647

Thai

land

Jan

2010

ndashDec

20

14Co

hort

5 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash15

yea

rs11

719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

CLSI

dat

e N

S

Shar

ma

et a

l 20

1648

Indi

aJa

n 20

13ndashA

ug

2014

Obs

erva

tiona

l1

year

7

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

1449

101

6661

1449

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

NCC

LS d

ate

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Tsai

et a

l 20

1649

Taiw

an C

hina

Jan

2001

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20

12Ca

sendashc

ontro

l12

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

350

7731

614

542

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

201

2

Chen

et a

l 20

1750

Taiw

an C

hina

Jan

2004

ndashJul

20

15Cr

oss-

sect

iona

l11

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

275

2219

27E

coli

Not

spec

ifyN

S

He

et a

l 20

1751

Chin

aM

ar 2

011ndash

Jun

2016

Coho

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s 3

mon

ths

Hos

pita

lLo

wer

resp

irato

ry

tract

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ctio

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utum

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onth

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ears

236

6472

4723

60E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stCL

SI d

ate

NS

Kim

et a

l 20

1752

Repu

blic

of

Kore

aJa

n 20

10ndashJ

un

2015

Coho

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year

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mon

ths

Hos

pita

lBa

cter

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iaBl

ood

le 1

7 ye

ars

185

4993

3518

5E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stN

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200

1

Man

dal e

t al

2017

53In

dia

Two

cons

ecut

ive

year

Coho

rt2

year

sCo

mm

unity

Dia

rrhoe

aSt

ool

0ndash60

mon

ths

633

7211

938

633

E co

liM

odifi

ed K

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r disk

diff

usio

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ate

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Nish

a et

al

2017

54In

dia

Nov

201

2ndashM

ar

2016

Coho

rt4

year

s 5

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

3 m

onth

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ye

ars

523

196

327

3852

3E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

201

0

Tsai

et a

l 20

1755

Taiw

an C

hina

2010

ndash201

4O

bser

vatio

nal

5 ye

ars

Hos

pita

lBa

cter

aem

iaBl

ood

lt 3

yea

rs41

1427

3441

E co

liN

SN

SBu

njou

ngm

anee

et a

l 20

1856

Thai

land

Jun

2016

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20

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l1

year

Hos

pita

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com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

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onth

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ears

8040

4023

80E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

0

Kita

gaw

a et

al

2018

57In

done

sia a

nd

Japa

nJa

nndashN

ov 2

014

Case

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trol

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tal amp

co

mm

unity

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ary

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in

fect

ion

Urin

e0ndash

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ears

9437

1339

94E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

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dat

e N

S

Wee

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ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

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hort

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onth

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tal

Vario

usVa

rious

Neo

nate

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188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

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CDC

Cen

ters

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e Co

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vent

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ical

and

Lab

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dard

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titut

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ende

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atio

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for C

linic

al L

abor

ator

y St

anda

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NS

not

spec

ified

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ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

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spp

Acin

etob

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r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6



Tabl

e 5

Ri

sk o

f bia

s in

coho

rt st

udie

s inc

lude

d in

the

met

a-an

alys

is of

ext

ende

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01

00

11

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l 20

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10

01

11

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uang

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l 20

0724

00

10

01

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in amp

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dal 2

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10

01

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e et

al

2007

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01

00

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al e

t al

2007

280

01

00

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14

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tach

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e et

al

2008

290

01

00

11

14

Anan

dan

et a

l 20

0930

00

10

01

11

4Ki

m e

t al

2009

310

01

00

11

14

Shak

il et

al

2010

321

01

00

11

15

Liu

et a

l 20

1134

00

10

01

11

4W

ei e

t al

2011

350

01

00

11

14

Zhen

g et

al

2012

370

01

00

11

14

Vija

yaka

nthi

et a

l 20

1338

00

10

01

11

5Th

emph

acha

na e

t al

2014

400

01

00

11

14

Duo

ng e

t al

2015

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00

11

14

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et a

l 20

1517

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6

Map

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Резюме



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(con

tinue

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Tabl

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Ch

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Stud

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2015

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201

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n 20

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Com

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Agar

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719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

CLSI

dat

e N

S

Shar

ma

et a

l 20

1648

Indi

aJa

n 20

13ndashA

ug

2014

Obs

erva

tiona

l1

year

7

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

1449

101

6661

1449

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

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LS d

ate

NS

Tsai

et a

l 20

1649

Taiw

an C

hina

Jan

2001

ndashDec

20

12Ca

sendashc

ontro

l12

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

350

7731

614

542

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

CLSI

201

2

Chen

et a

l 20

1750

Taiw

an C

hina

Jan

2004

ndashJul

20

15Cr

oss-

sect

iona

l11

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

275

2219

27E

coli

Not

spec

ifyN

S

He

et a

l 20

1751

Chin

aM

ar 2

011ndash

Jun

2016

Coho

rt4

year

s 3

mon

ths

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

1 m

onth

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ears

236

6472

4723

60E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stCL

SI d

ate

NS

Kim

et a

l 20

1752

Repu

blic

of

Kore

aJa

n 20

10ndashJ

un

2015

Coho

rt5

year

s 5

mon

ths

Hos

pita

lBa

cter

aem

iaBl

ood

le 1

7 ye

ars

185

4993

3518

5E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stN

CCLS

200

1

Man

dal e

t al

2017

53In

dia

Two

cons

ecut

ive

year

Coho

rt2

year

sCo

mm

unity

Dia

rrhoe

aSt

ool

0ndash60

mon

ths

633

7211

938

633

E co

liM

odifi

ed K

irby-

Baue

r disk

diff

usio

nCL

SI d

ate

NS

Nish

a et

al

2017

54In

dia

Nov

201

2ndashM

ar

2016

Coho

rt4

year

s 5

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

3 m

onth

sndash18

ye

ars

523

196

327

3852

3E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

201

0

Tsai

et a

l 20

1755

Taiw

an C

hina

2010

ndash201

4O

bser

vatio

nal

5 ye

ars

Hos

pita

lBa

cter

aem

iaBl

ood

lt 3

yea

rs41

1427

3441

E co

liN

SN

SBu

njou

ngm

anee

et a

l 20

1856

Thai

land

Jun

2016

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20

17Ca

sendashc

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l1

year

Hos

pita

l amp

com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

1 m

onth

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ears

8040

4023

80E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

0

Kita

gaw

a et

al

2018

57In

done

sia a

nd

Japa

nJa

nndashN

ov 2

014

Case

ndashcon

trol

1 ye

arH

ospi

tal amp

co

mm

unity

Urin

ary

tract

in

fect

ion

Urin

e0ndash

15 y

ears

9437

1339

94E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Wee

rasin

ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

1Co

hort

3 m

onth

sH

ospi

tal

Vario

usVa

rious

Neo

nate

s50

188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

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SI amp

CD

C 2

011

CDC

Cen

ters

for D

iseas

e Co

ntro

l and

Pre

vent

ion

CLS

I Clin

ical

and

Lab

orat

ory

Stan

dard

s Ins

titut

e E

SBL

ext

ende

d-sp

ectru

m β

-lact

amas

e-pr

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ing

bact

eria

NCC

LS N

atio

nal C

omm

ittee

for C

linic

al L

abor

ator

y St

anda

rds

NS

not

spec

ified

a M

ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

onas

spp

Acin

etob

acte

r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6











Pooled preva-lence

No of people

No () ESBL-positive

No of people

No () ESBL-positive


















Fig

6

Map

of p

reva

lenc

e of

ext

ende

d-sp

ectr

um β

-lact

amas

e-as

socia

ted

infe

ctio

n in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s

087

517

503

500

kmN

Prev

alen

ce o

f ES

BL-a

ssoc

iate

d in

fect

ion

10

0-80

80ndash6

060

ndash40

40ndash2

020

ndash0N

o da

ta

Adul

ts an

d ch

ildre

nCh

ildre

n

ESBL

ext

ende

d-sp

ectru

m β

-lact

amas

eN

otes

We

pool

ed d

ata

from

a se

arch

of t

he p

ublis

hed

and

grey

lite

ratu

re fo

r sur

veill

ance

dat

a fro

m a

ll M

embe

r Sta

tes a

nd a

reas

in th

e W

orld

Hea

lth O

rgan

izat

ion

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c Re

gion

s Th

e m

ap fo

r adu

lts a

nd c

hild

ren

incl

udes

dat

a fro

m A

ustra

lia B

huta

n B

rune

i Dar

ussa

lam

Cam

bodi

a Ta

iwan

Chi

na C

hina

Hon

g Ko

ng S

peci

al A

dmin

istra

tive

Regi

on I

ndia

Ind

ones

ia J

apan

Fed

erat

ed S

tate

s of M

icro

nesia

(Fed

erat

ed S

tate

s of)

Mya

nmar

Nep

al N

ew Z

eala

nd

Papu

a N

ew G

uine

a P

hilip

pine

s Re

publ

ic o

f Kor

ea S

inga

pore

Tha

iland

and

Vie

t Nam

The

map

for c

hild

ren

only

(age

s 0ndash2

1 ye

ars)

incl

udes

dat

a fro

m A

ustra

lia (2

5

) Ch

ina

(54

3)

Taiw

an C

hina

(28

7)

Indi

a (4

59

) In

done

sia (3

90

) Ja

pan

(90

)

New

Zea

land

(28

)

Repu

blic

of K

orea

(23

7)

Sing

apor

e (4

0

) Sr

i Lan

ka (3

60

) Th

aila

nd (2

17

) an

d Vi

et N

am (3

95

)



















Reacutesumeacute
















Резюме



Resumen





























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash17

yea

rs14

249

9317

157

Esch

eric

hia

coli

Kleb

siella

pn

eum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Jain

et a

l 20

0321

Indi

a1

year

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

728

165

3679

400

E co

li K

pne

umon

iae

Ente

roba

cter

sp

pD

oubl

e di

sk sy

nerg

y te

stCL

SI 2

000

amp N

CCLS

dat

e N

SBo

o et

al

2005

22M

alay

sia19

96ndashO

ct 2

002

Case

ndashcon

trol

7 ye

ars

Hos

pita

lSe

psis

Vario

usN

eona

tes

350

8080

2236

9K

pne

umon

iae

Ente

roba

cter

spp

Dou

ble

disk

di

ffusio

nM

inist

ry o

f Hea

lth

of M

alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

ndashDec

20

01Co

hort

1 ye

arH

ospi

tal

Nos

ocom

ial

infe

ctio

nVa

rious

Neo

nate

s76

3442

4476

E co

li K

pne

umon

iae

KSD

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Hua

ng e

t al

2007

24Ch

ina

Jan

2000

ndashDec

20

02Co

hort

3 ye

ars

Hos

pita

lN

osoc

omia

l in

fect

ion

Vario

usN

eona

tes

3922

1756

2358

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nN

CCLS

200

0

Jain

amp M

onda

l 200

725b

Indi

aJa

n 20

04ndashD

ec

2005

Coho

rt2

year

sH

ospi

tal

Seps

isBl

ood

Neo

nate

s10

058

4258

2995

K p

neum

onia

e En

tero

bact

er sp

pD

oubl

e di

sk

diffu

sion

NCC

LS 2

003

Kuo

et a

l 20

0726

Taiw

an C

hina

Jan

2000

ndashOct

20

05Ca

sendashc

ontro

l5

year

s 9

mon

ths

Hos

pita

lVa

rious

Vario

usBi

rth

to N

S10

854

5428

274

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Lee

et a

l 20

0727

Repu

blic

of

Kore

aJa

n 19

99ndashD

ec

2005

Coho

rt7

year

sH

ospi

tal

Vario

usVa

rious

NS

228

3554

2925

2E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

st V

itek-

GNI c

ard

CLSI

200

5

Sehg

al e

t al

2007

28In

dia

April

200

2ndashM

ay

2003

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

7538

2561

75M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Bhat

tach

arje

e et

al

2008

29b

Indi

a14

mon

ths

Coho

rt1

year

2

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

243

2658

3224

3M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

CLSI

200

8

Anan

dan

et a

l 20

0930

bIn

dia

Jan

2003

ndashDec

20

07Co

hort

5 ye

ars

Hos

pita

lSe

psis

Bloo

dN

eona

tes

9468

2672

8330

E co

li K

pne

umon

iae

Not

spec

ifyCL

SI 2

008

Kim

et a

l 20

0931

Repu

blic

of

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aJa

n 20

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pr

2009

Coho

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ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

Child

ren

854

3283

1768

1E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

S

Shak

il et

al

2010

32In

dia

Jan

2006

ndashFeb

20

07Co

hort

1 ye

ars

Hos

pita

lVa

rious

Vario

usN

eona

tes

238

104

107

4446

9E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Gau

rav

et a

l 20

1133

Indi

aM

ay 2

007ndash

Apr

2008

Case

ndashcon

trol

1 ye

arH

ospi

tal

Seps

isBl

ood

Neo

nate

s34

450

5236

5116

E co

li K

pne

umon

iae

Dou

ble

disk

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ffusio

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ate

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Liu

et a

l 20

1134

Chin

aFe

b 20

09ndashJ

an

2011

Coho

rt2

year

sH

ospi

tal

Low

er re

spira

tory

tra

ct in

fect

ion

Sput

umlt

3 y

ears

242

9414

839

242

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

dat

e N

S

Wei

et a

l 20

1135

Chin

aJa

n 20

09ndashD

ec

2009

Obs

erva

tiona

l1

year

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

lt 1

yea

r27

214

412

853

1380

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

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200

9

Min

ami e

t al

2012

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pan

July

201

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day

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oss-

sect

iona

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day

Hos

pita

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rious

Rect

alle

12

year

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446

1262

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

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200

8

Zhen

g et

al

2012

37Ch

ina

2002

ndash200

8Co

hort

6 ye

ars

Hos

pita

lH

aem

atol

ogic

al

mal

igna

ncy

Bloo

dlt

16

year

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919

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3264

E co

li K

pne

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k 60

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dat

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Vija

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l 20

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Indi

aD

ec 2

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Nov

20

10Co

hort

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tal

Seps

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rious

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Mul

tiple

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iesa

Dou

ble

disk

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ffusio

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ate

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Fan

et a

l 201

439Ta

iwan

Chi

na20

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006

Case

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trol

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ars

Com

mun

ityU

rinar

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ct

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ctio

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rine

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ars

312

104

208

3364

67E

coli

Dou

ble

disk

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ffusio

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007

Them

phac

hana

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l 20

1440

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land

Febndash

Sep

2013

Obs

erva

tiona

l8

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 2

1 ye

ars

166

8283

2616

6E

coli

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neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

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Youn

g et

al

2014

41Si

ngap

ore

Nov

200

6ndashFe

b 20

07O

bser

vatio

nal

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mm

unity

Vario

usVa

rious

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1006

6912

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1006

ESBL

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taph

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eus

vanc

omyc

in-re

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nt E

nter

ococ

cus

spp

Dou

ble

disk

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Zuo

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l 20

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Chin

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Obs

erva

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year

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pita

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e Ki

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r disk

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Duo

ng e

t al

2015

43Vi

et N

amJu

l 201

1ndashN

ov

2012

Coho

rt1

year

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mon

ths

Hos

pita

lU

rinar

y tra

ct

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ctio

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rious

3 m

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ye

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216

2217

5214

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e di

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sion

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Han

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ic o

f Ko

rea

Apr 2

009ndash

Mar

20

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hort

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ars

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pita

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ia

(febr

ile)

Bloo

dlt

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year

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3461

E co

li K

pne

umon

iae

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k 2

syst

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Han

et a

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publ

ic o

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rea

Jan

2010

ndashDec

20

14Co

hort

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Hos

pita

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rinar

y tra

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infe

ctio

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8 ye

ars

205

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E co

li K

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S



Auth

orCo

untr

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Figure 1

Table 2

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Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6



Fig

6

Map

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ende

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)



















Reacutesumeacute
















Резюме



Resumen





























































































(con

tinue

s

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Tabl

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utum

1ndash3

mon

ths

622

9394

7937

9E

coli

K p

neum

onia

e Ki

rby-

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r disk

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ffusio

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SI 2

012

Duo

ng e

t al

2015

43Vi

et N

amJu

l 201

1ndashN

ov

2012

Coho

rt1

year

4

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nVa

rious

3 m

onth

sndash15

ye

ars

216

2217

5214

3E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

200

7

Han

et a

l 20

1517

cRe

publ

ic o

f Ko

rea

Apr 2

009ndash

Mar

20

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hort

4 ye

ars

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pita

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ia

(febr

ile)

Bloo

dlt

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year

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E co

li K

pne

umon

iae

Vite

k 2

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S

Han

et a

l 20

1544

dRe

publ

ic o

f Ko

rea

Jan

2010

ndashDec

20

14Co

hort

4 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 1

8 ye

ars

205

2218

910

211

E co

li K

pne

umon

iae

Vite

k 2

syst

emN

S



Auth

orCo

untr

y or a

rea

Stud

y dat

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udy d

esig

nSt

udy

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tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

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eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Nish

a et

al

2015

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dia

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201

2ndashJa

n 20

15Co

hort

3 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

le 1

8 ye

ars

385

159

226

4138

5E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

dat

e N

S

Agar

wal

et a

l 20

16 46

bIn

dia

2009

ndash201

2Co

hort

4 ye

ars

Hos

pita

lD

iarrh

oea

Stoo

lYo

ung

child

ren

6339

2398

1963

39E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

SAm

ornc

haic

haro

ensu

k 2

01647

Thai

land

Jan

2010

ndashDec

20

14Co

hort

5 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash15

yea

rs11

719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

CLSI

dat

e N

S

Shar

ma

et a

l 20

1648

Indi

aJa

n 20

13ndashA

ug

2014

Obs

erva

tiona

l1

year

7

mon

ths

Hos

pita

lSe

psis

Bloo

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tes

1449

101

6661

1449

Mul

tiple

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iesa

Dou

ble

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rgy

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LS d

ate

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Tsai

et a

l 20

1649

Taiw

an C

hina

Jan

2001

ndashDec

20

12Ca

sendashc

ontro

l12

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

350

7731

614

542

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

CLSI

201

2

Chen

et a

l 20

1750

Taiw

an C

hina

Jan

2004

ndashJul

20

15Cr

oss-

sect

iona

l11

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

275

2219

27E

coli

Not

spec

ifyN

S

He

et a

l 20

1751

Chin

aM

ar 2

011ndash

Jun

2016

Coho

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year

s 3

mon

ths

Hos

pita

lLo

wer

resp

irato

ry

tract

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ctio

nSp

utum

1 m

onth

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ears

236

6472

4723

60E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stCL

SI d

ate

NS

Kim

et a

l 20

1752

Repu

blic

of

Kore

aJa

n 20

10ndashJ

un

2015

Coho

rt5

year

s 5

mon

ths

Hos

pita

lBa

cter

aem

iaBl

ood

le 1

7 ye

ars

185

4993

3518

5E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stN

CCLS

200

1

Man

dal e

t al

2017

53In

dia

Two

cons

ecut

ive

year

Coho

rt2

year

sCo

mm

unity

Dia

rrhoe

aSt

ool

0ndash60

mon

ths

633

7211

938

633

E co

liM

odifi

ed K

irby-

Baue

r disk

diff

usio

nCL

SI d

ate

NS

Nish

a et

al

2017

54In

dia

Nov

201

2ndashM

ar

2016

Coho

rt4

year

s 5

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

3 m

onth

sndash18

ye

ars

523

196

327

3852

3E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

201

0

Tsai

et a

l 20

1755

Taiw

an C

hina

2010

ndash201

4O

bser

vatio

nal

5 ye

ars

Hos

pita

lBa

cter

aem

iaBl

ood

lt 3

yea

rs41

1427

3441

E co

liN

SN

SBu

njou

ngm

anee

et a

l 20

1856

Thai

land

Jun

2016

ndashMay

20

17Ca

sendashc

ontro

l1

year

Hos

pita

l amp

com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

1 m

onth

ndash5 y

ears

8040

4023

80E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

0

Kita

gaw

a et

al

2018

57In

done

sia a

nd

Japa

nJa

nndashN

ov 2

014

Case

ndashcon

trol

1 ye

arH

ospi

tal amp

co

mm

unity

Urin

ary

tract

in

fect

ion

Urin

e0ndash

15 y

ears

9437

1339

94E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Wee

rasin

ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

1Co

hort

3 m

onth

sH

ospi

tal

Vario

usVa

rious

Neo

nate

s50

188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

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SI amp

CD

C 2

011

CDC

Cen

ters

for D

iseas

e Co

ntro

l and

Pre

vent

ion

CLS

I Clin

ical

and

Lab

orat

ory

Stan

dard

s Ins

titut

e E

SBL

ext

ende

d-sp

ectru

m β

-lact

amas

e-pr

oduc

ing

bact

eria

NCC

LS N

atio

nal C

omm

ittee

for C

linic

al L

abor

ator

y St

anda

rds

NS

not

spec

ified

a M

ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

onas

spp

Acin

etob

acte

r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

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trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6



















Reacutesumeacute
















Резюме



Resumen





























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

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eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

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sitiv

eES

BL-

nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash17

yea

rs14

249

9317

157

Esch

eric

hia

coli

Kleb

siella

pn

eum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Jain

et a

l 20

0321

Indi

a1

year

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

728

165

3679

400

E co

li K

pne

umon

iae

Ente

roba

cter

sp

pD

oubl

e di

sk sy

nerg

y te

stCL

SI 2

000

amp N

CCLS

dat

e N

SBo

o et

al

2005

22M

alay

sia19

96ndashO

ct 2

002

Case

ndashcon

trol

7 ye

ars

Hos

pita

lSe

psis

Vario

usN

eona

tes

350

8080

2236

9K

pne

umon

iae

Ente

roba

cter

spp

Dou

ble

disk

di

ffusio

nM

inist

ry o

f Hea

lth

of M

alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

ndashDec

20

01Co

hort

1 ye

arH

ospi

tal

Nos

ocom

ial

infe

ctio

nVa

rious

Neo

nate

s76

3442

4476

E co

li K

pne

umon

iae

KSD

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Hua

ng e

t al

2007

24Ch

ina

Jan

2000

ndashDec

20

02Co

hort

3 ye

ars

Hos

pita

lN

osoc

omia

l in

fect

ion

Vario

usN

eona

tes

3922

1756

2358

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nN

CCLS

200

0

Jain

amp M

onda

l 200

725b

Indi

aJa

n 20

04ndashD

ec

2005

Coho

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year

sH

ospi

tal

Seps

isBl

ood

Neo

nate

s10

058

4258

2995

K p

neum

onia

e En

tero

bact

er sp

pD

oubl

e di

sk

diffu

sion

NCC

LS 2

003

Kuo

et a

l 20

0726

Taiw

an C

hina

Jan

2000

ndashOct

20

05Ca

sendashc

ontro

l5

year

s 9

mon

ths

Hos

pita

lVa

rious

Vario

usBi

rth

to N

S10

854

5428

274

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

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LS 2

001

Lee

et a

l 20

0727

Repu

blic

of

Kore

aJa

n 19

99ndashD

ec

2005

Coho

rt7

year

sH

ospi

tal

Vario

usVa

rious

NS

228

3554

2925

2E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

st V

itek-

GNI c

ard

CLSI

200

5

Sehg

al e

t al

2007

28In

dia

April

200

2ndashM

ay

2003

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

7538

2561

75M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Bhat

tach

arje

e et

al

2008

29b

Indi

a14

mon

ths

Coho

rt1

year

2

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

243

2658

3224

3M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

CLSI

200

8

Anan

dan

et a

l 20

0930

bIn

dia

Jan

2003

ndashDec

20

07Co

hort

5 ye

ars

Hos

pita

lSe

psis

Bloo

dN

eona

tes

9468

2672

8330

E co

li K

pne

umon

iae

Not

spec

ifyCL

SI 2

008

Kim

et a

l 20

0931

Repu

blic

of

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aJa

n 20

04ndashA

pr

2009

Coho

rt5

year

s 2

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

Child

ren

854

3283

1768

1E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

S

Shak

il et

al

2010

32In

dia

Jan

2006

ndashFeb

20

07Co

hort

1 ye

ars

Hos

pita

lVa

rious

Vario

usN

eona

tes

238

104

107

4446

9E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Gau

rav

et a

l 20

1133

Indi

aM

ay 2

007ndash

Apr

2008

Case

ndashcon

trol

1 ye

arH

ospi

tal

Seps

isBl

ood

Neo

nate

s34

450

5236

5116

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI d

ate

NS

Liu

et a

l 20

1134

Chin

aFe

b 20

09ndashJ

an

2011

Coho

rt2

year

sH

ospi

tal

Low

er re

spira

tory

tra

ct in

fect

ion

Sput

umlt

3 y

ears

242

9414

839

242

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

CLSI

dat

e N

S

Wei

et a

l 20

1135

Chin

aJa

n 20

09ndashD

ec

2009

Obs

erva

tiona

l1

year

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

lt 1

yea

r27

214

412

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1380

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

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200

9

Min

ami e

t al

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pan

July

201

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day

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oss-

sect

iona

l1

day

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pita

lVa

rious

Rect

alle

12

year

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446

1262

Mul

tiple

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iesa

Dou

ble

disk

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rgy

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200

8

Zhen

g et

al

2012

37Ch

ina

2002

ndash200

8Co

hort

6 ye

ars

Hos

pita

lH

aem

atol

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al

mal

igna

ncy

Bloo

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year

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3264

E co

li K

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k 60

syst

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dat

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S

Vija

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l 20

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Nov

20

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hort

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tal

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rious

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nate

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Mul

tiple

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ble

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ffusio

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ate

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Fan

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l 201

439Ta

iwan

Chi

na20

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Case

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ars

Com

mun

ityU

rinar

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ct

infe

ctio

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rine

lt 1

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ars

312

104

208

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coli

Dou

ble

disk

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ffusio

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007

Them

phac

hana

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l 20

1440

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land

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Sep

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Obs

erva

tiona

l8

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 2

1 ye

ars

166

8283

2616

6E

coli

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neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

2

Youn

g et

al

2014

41Si

ngap

ore

Nov

200

6ndashFe

b 20

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bser

vatio

nal

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unity

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usVa

rious

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ars

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ng

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ae m

ethi

cilli

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sista

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taph

yloc

occu

s aur

eus

vanc

omyc

in-re

sista

nt E

nter

ococ

cus

spp

Dou

ble

disk

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ffusio

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l 20

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aJa

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ec 2

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Obs

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Hos

pita

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ctio

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utum

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ths

622

9394

7937

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coli

K p

neum

onia

e Ki

rby-

Baue

r disk

di

ffusio

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SI 2

012

Duo

ng e

t al

2015

43Vi

et N

amJu

l 201

1ndashN

ov

2012

Coho

rt1

year

4

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nVa

rious

3 m

onth

sndash15

ye

ars

216

2217

5214

3E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

200

7

Han

et a

l 20

1517

cRe

publ

ic o

f Ko

rea

Apr 2

009ndash

Mar

20

13Co

hort

4 ye

ars

Hos

pita

lN

eutro

poen

ia

(febr

ile)

Bloo

dlt

20

year

s61

2140

3461

E co

li K

pne

umon

iae

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S

Han

et a

l 20

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publ

ic o

f Ko

rea

Jan

2010

ndashDec

20

14Co

hort

4 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 1

8 ye

ars

205

2218

910

211

E co

li K

pne

umon

iae

Vite

k 2

syst

emN

S



Auth

orCo

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y or a

rea

Stud

y dat

esSt

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esig

nSt

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dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

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sitiv

eES

BL-

nega

tive

Nish

a et

al

2015

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dia

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201

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n 20

15Co

hort

3 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

le 1

8 ye

ars

385

159

226

4138

5E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

dat

e N

S

Agar

wal

et a

l 20

16 46

bIn

dia

2009

ndash201

2Co

hort

4 ye

ars

Hos

pita

lD

iarrh

oea

Stoo

lYo

ung

child

ren

6339

2398

1963

39E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

SAm

ornc

haic

haro

ensu

k 2

01647

Thai

land

Jan

2010

ndashDec

20

14Co

hort

5 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash15

yea

rs11

719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

CLSI

dat

e N

S

Shar

ma

et a

l 20

1648

Indi

aJa

n 20

13ndashA

ug

2014

Obs

erva

tiona

l1

year

7

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

1449

101

6661

1449

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

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LS d

ate

NS

Tsai

et a

l 20

1649

Taiw

an C

hina

Jan

2001

ndashDec

20

12Ca

sendashc

ontro

l12

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

350

7731

614

542

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

201

2

Chen

et a

l 20

1750

Taiw

an C

hina

Jan

2004

ndashJul

20

15Cr

oss-

sect

iona

l11

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

275

2219

27E

coli

Not

spec

ifyN

S

He

et a

l 20

1751

Chin

aM

ar 2

011ndash

Jun

2016

Coho

rt4

year

s 3

mon

ths

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

1 m

onth

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ears

236

6472

4723

60E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stCL

SI d

ate

NS

Kim

et a

l 20

1752

Repu

blic

of

Kore

aJa

n 20

10ndashJ

un

2015

Coho

rt5

year

s 5

mon

ths

Hos

pita

lBa

cter

aem

iaBl

ood

le 1

7 ye

ars

185

4993

3518

5E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stN

CCLS

200

1

Man

dal e

t al

2017

53In

dia

Two

cons

ecut

ive

year

Coho

rt2

year

sCo

mm

unity

Dia

rrhoe

aSt

ool

0ndash60

mon

ths

633

7211

938

633

E co

liM

odifi

ed K

irby-

Baue

r disk

diff

usio

nCL

SI d

ate

NS

Nish

a et

al

2017

54In

dia

Nov

201

2ndashM

ar

2016

Coho

rt4

year

s 5

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

3 m

onth

sndash18

ye

ars

523

196

327

3852

3E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

201

0

Tsai

et a

l 20

1755

Taiw

an C

hina

2010

ndash201

4O

bser

vatio

nal

5 ye

ars

Hos

pita

lBa

cter

aem

iaBl

ood

lt 3

yea

rs41

1427

3441

E co

liN

SN

SBu

njou

ngm

anee

et a

l 20

1856

Thai

land

Jun

2016

ndashMay

20

17Ca

sendashc

ontro

l1

year

Hos

pita

l amp

com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

1 m

onth

ndash5 y

ears

8040

4023

80E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

0

Kita

gaw

a et

al

2018

57In

done

sia a

nd

Japa

nJa

nndashN

ov 2

014

Case

ndashcon

trol

1 ye

arH

ospi

tal amp

co

mm

unity

Urin

ary

tract

in

fect

ion

Urin

e0ndash

15 y

ears

9437

1339

94E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Wee

rasin

ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

1Co

hort

3 m

onth

sH

ospi

tal

Vario

usVa

rious

Neo

nate

s50

188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI amp

CD

C 2

011

CDC

Cen

ters

for D

iseas

e Co

ntro

l and

Pre

vent

ion

CLS

I Clin

ical

and

Lab

orat

ory

Stan

dard

s Ins

titut

e E

SBL

ext

ende

d-sp

ectru

m β

-lact

amas

e-pr

oduc

ing

bact

eria

NCC

LS N

atio

nal C

omm

ittee

for C

linic

al L

abor

ator

y St

anda

rds

NS

not

spec

ified

a M

ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

onas

spp

Acin

etob

acte

r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6





Резюме



Resumen





























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash17

yea

rs14

249

9317

157

Esch

eric

hia

coli

Kleb

siella

pn

eum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Jain

et a

l 20

0321

Indi

a1

year

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

728

165

3679

400

E co

li K

pne

umon

iae

Ente

roba

cter

sp

pD

oubl

e di

sk sy

nerg

y te

stCL

SI 2

000

amp N

CCLS

dat

e N

SBo

o et

al

2005

22M

alay

sia19

96ndashO

ct 2

002

Case

ndashcon

trol

7 ye

ars

Hos

pita

lSe

psis

Vario

usN

eona

tes

350

8080

2236

9K

pne

umon

iae

Ente

roba

cter

spp

Dou

ble

disk

di

ffusio

nM

inist

ry o

f Hea

lth

of M

alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

ndashDec

20

01Co

hort

1 ye

arH

ospi

tal

Nos

ocom

ial

infe

ctio

nVa

rious

Neo

nate

s76

3442

4476

E co

li K

pne

umon

iae

KSD

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Hua

ng e

t al

2007

24Ch

ina

Jan

2000

ndashDec

20

02Co

hort

3 ye

ars

Hos

pita

lN

osoc

omia

l in

fect

ion

Vario

usN

eona

tes

3922

1756

2358

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nN

CCLS

200

0

Jain

amp M

onda

l 200

725b

Indi

aJa

n 20

04ndashD

ec

2005

Coho

rt2

year

sH

ospi

tal

Seps

isBl

ood

Neo

nate

s10

058

4258

2995

K p

neum

onia

e En

tero

bact

er sp

pD

oubl

e di

sk

diffu

sion

NCC

LS 2

003

Kuo

et a

l 20

0726

Taiw

an C

hina

Jan

2000

ndashOct

20

05Ca

sendashc

ontro

l5

year

s 9

mon

ths

Hos

pita

lVa

rious

Vario

usBi

rth

to N

S10

854

5428

274

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Lee

et a

l 20

0727

Repu

blic

of

Kore

aJa

n 19

99ndashD

ec

2005

Coho

rt7

year

sH

ospi

tal

Vario

usVa

rious

NS

228

3554

2925

2E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

st V

itek-

GNI c

ard

CLSI

200

5

Sehg

al e

t al

2007

28In

dia

April

200

2ndashM

ay

2003

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

7538

2561

75M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Bhat

tach

arje

e et

al

2008

29b

Indi

a14

mon

ths

Coho

rt1

year

2

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

243

2658

3224

3M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

CLSI

200

8

Anan

dan

et a

l 20

0930

bIn

dia

Jan

2003

ndashDec

20

07Co

hort

5 ye

ars

Hos

pita

lSe

psis

Bloo

dN

eona

tes

9468

2672

8330

E co

li K

pne

umon

iae

Not

spec

ifyCL

SI 2

008

Kim

et a

l 20

0931

Repu

blic

of

Kore

aJa

n 20

04ndashA

pr

2009

Coho

rt5

year

s 2

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

Child

ren

854

3283

1768

1E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

S

Shak

il et

al

2010

32In

dia

Jan

2006

ndashFeb

20

07Co

hort

1 ye

ars

Hos

pita

lVa

rious

Vario

usN

eona

tes

238

104

107

4446

9E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Gau

rav

et a

l 20

1133

Indi

aM

ay 2

007ndash

Apr

2008

Case

ndashcon

trol

1 ye

arH

ospi

tal

Seps

isBl

ood

Neo

nate

s34

450

5236

5116

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI d

ate

NS

Liu

et a

l 20

1134

Chin

aFe

b 20

09ndashJ

an

2011

Coho

rt2

year

sH

ospi

tal

Low

er re

spira

tory

tra

ct in

fect

ion

Sput

umlt

3 y

ears

242

9414

839

242

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

CLSI

dat

e N

S

Wei

et a

l 20

1135

Chin

aJa

n 20

09ndashD

ec

2009

Obs

erva

tiona

l1

year

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

lt 1

yea

r27

214

412

853

1380

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

200

9

Min

ami e

t al

2012

36Ja

pan

July

201

1 (1

day

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oss-

sect

iona

l1

day

Hos

pita

lVa

rious

Rect

alle

12

year

s50

446

1262

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

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200

8

Zhen

g et

al

2012

37Ch

ina

2002

ndash200

8Co

hort

6 ye

ars

Hos

pita

lH

aem

atol

ogic

al

mal

igna

ncy

Bloo

dlt

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year

s10

919

3852

3264

E co

li K

pne

umon

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k 60

syst

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dat

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S

Vija

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nthi

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l 20

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Nov

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rious

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Mul

tiple

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iesa

Dou

ble

disk

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ffusio

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ate

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Fan

et a

l 201

439Ta

iwan

Chi

na20

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Case

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4 ye

ars

Com

mun

ityU

rinar

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ct

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ctio

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rine

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ars

312

104

208

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Dou

ble

disk

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ffusio

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phac

hana

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l 20

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land

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Sep

2013

Obs

erva

tiona

l8

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 2

1 ye

ars

166

8283

2616

6E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

2

Youn

g et

al

2014

41Si

ngap

ore

Nov

200

6ndashFe

b 20

07O

bser

vatio

nal

3 m

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unity

Vario

usVa

rious

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ars

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ng

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roba

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ethi

cilli

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sista

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taph

yloc

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s aur

eus

vanc

omyc

in-re

sista

nt E

nter

ococ

cus

spp

Dou

ble

disk

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ffusio

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et a

l 20

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aJa

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013

Obs

erva

tiona

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ths

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coli

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onia

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r disk

di

ffusio

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012

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ng e

t al

2015

43Vi

et N

amJu

l 201

1ndashN

ov

2012

Coho

rt1

year

4

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nVa

rious

3 m

onth

sndash15

ye

ars

216

2217

5214

3E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

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200

7

Han

et a

l 20

1517

cRe

publ

ic o

f Ko

rea

Apr 2

009ndash

Mar

20

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hort

4 ye

ars

Hos

pita

lN

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ia

(febr

ile)

Bloo

dlt

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year

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3461

E co

li K

pne

umon

iae

Vite

k 2

syst

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S

Han

et a

l 20

1544

dRe

publ

ic o

f Ko

rea

Jan

2010

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20

14Co

hort

4 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

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8 ye

ars

205

2218

910

211

E co

li K

pne

umon

iae

Vite

k 2

syst

emN

S



Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Nish

a et

al

2015

45In

dia

Nov

201

2ndashJa

n 20

15Co

hort

3 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

le 1

8 ye

ars

385

159

226

4138

5E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

dat

e N

S

Agar

wal

et a

l 20

16 46

bIn

dia

2009

ndash201

2Co

hort

4 ye

ars

Hos

pita

lD

iarrh

oea

Stoo

lYo

ung

child

ren

6339

2398

1963

39E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

SAm

ornc

haic

haro

ensu

k 2

01647

Thai

land

Jan

2010

ndashDec

20

14Co

hort

5 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash15

yea

rs11

719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

CLSI

dat

e N

S

Shar

ma

et a

l 20

1648

Indi

aJa

n 20

13ndashA

ug

2014

Obs

erva

tiona

l1

year

7

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

1449

101

6661

1449

Mul

tiple

spec

iesa

Dou

ble

disk

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rgy

test

NCC

LS d

ate

NS

Tsai

et a

l 20

1649

Taiw

an C

hina

Jan

2001

ndashDec

20

12Ca

sendashc

ontro

l12

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

350

7731

614

542

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

201

2

Chen

et a

l 20

1750

Taiw

an C

hina

Jan

2004

ndashJul

20

15Cr

oss-

sect

iona

l11

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

275

2219

27E

coli

Not

spec

ifyN

S

He

et a

l 20

1751

Chin

aM

ar 2

011ndash

Jun

2016

Coho

rt4

year

s 3

mon

ths

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

1 m

onth

ndash5 y

ears

236

6472

4723

60E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stCL

SI d

ate

NS

Kim

et a

l 20

1752

Repu

blic

of

Kore

aJa

n 20

10ndashJ

un

2015

Coho

rt5

year

s 5

mon

ths

Hos

pita

lBa

cter

aem

iaBl

ood

le 1

7 ye

ars

185

4993

3518

5E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

stN

CCLS

200

1

Man

dal e

t al

2017

53In

dia

Two

cons

ecut

ive

year

Coho

rt2

year

sCo

mm

unity

Dia

rrhoe

aSt

ool

0ndash60

mon

ths

633

7211

938

633

E co

liM

odifi

ed K

irby-

Baue

r disk

diff

usio

nCL

SI d

ate

NS

Nish

a et

al

2017

54In

dia

Nov

201

2ndashM

ar

2016

Coho

rt4

year

s 5

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

3 m

onth

sndash18

ye

ars

523

196

327

3852

3E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

201

0

Tsai

et a

l 20

1755

Taiw

an C

hina

2010

ndash201

4O

bser

vatio

nal

5 ye

ars

Hos

pita

lBa

cter

aem

iaBl

ood

lt 3

yea

rs41

1427

3441

E co

liN

SN

SBu

njou

ngm

anee

et a

l 20

1856

Thai

land

Jun

2016

ndashMay

20

17Ca

sendashc

ontro

l1

year

Hos

pita

l amp

com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

1 m

onth

ndash5 y

ears

8040

4023

80E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

0

Kita

gaw

a et

al

2018

57In

done

sia a

nd

Japa

nJa

nndashN

ov 2

014

Case

ndashcon

trol

1 ye

arH

ospi

tal amp

co

mm

unity

Urin

ary

tract

in

fect

ion

Urin

e0ndash

15 y

ears

9437

1339

94E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Wee

rasin

ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

1Co

hort

3 m

onth

sH

ospi

tal

Vario

usVa

rious

Neo

nate

s50

188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI amp

CD

C 2

011

CDC

Cen

ters

for D

iseas

e Co

ntro

l and

Pre

vent

ion

CLS

I Clin

ical

and

Lab

orat

ory

Stan

dard

s Ins

titut

e E

SBL

ext

ende

d-sp

ectru

m β

-lact

amas

e-pr

oduc

ing

bact

eria

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LS N

atio

nal C

omm

ittee

for C

linic

al L

abor

ator

y St

anda

rds

NS

not

spec

ified

a M

ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

onas

spp

Acin

etob

acte

r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6



























































































(con

tinue

s

)

Tabl

e 1

Ch

arac

teris

tics o

f 40

stud

ies i

nclu

ded

in th

e m

eta-

anal

ysis

of e

xten

ded-

spec

trum

β-la

ctam

ase-

asso

ciate

d in

fect

ion

amon

g ch

ildre

n an

d yo

ung

adul

ts in

Sout

h-Ea

st A

sia a

nd W

este

rn P

acifi

c cou

ntrie

s 20

02ndash2

018

Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Kim

et a

l 20

0220

Repu

blic

of

Kore

aN

ov 1

993ndash

Dec

19

98Co

hort

5 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash17

yea

rs14

249

9317

157

Esch

eric

hia

coli

Kleb

siella

pn

eum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Jain

et a

l 20

0321

Indi

a1

year

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

728

165

3679

400

E co

li K

pne

umon

iae

Ente

roba

cter

sp

pD

oubl

e di

sk sy

nerg

y te

stCL

SI 2

000

amp N

CCLS

dat

e N

SBo

o et

al

2005

22M

alay

sia19

96ndashO

ct 2

002

Case

ndashcon

trol

7 ye

ars

Hos

pita

lSe

psis

Vario

usN

eona

tes

350

8080

2236

9K

pne

umon

iae

Ente

roba

cter

spp

Dou

ble

disk

di

ffusio

nM

inist

ry o

f Hea

lth

of M

alay

sia 2

001

Chiu

et a

l 20

0523

Taiw

an C

hina

Jan

2001

ndashDec

20

01Co

hort

1 ye

arH

ospi

tal

Nos

ocom

ial

infe

ctio

nVa

rious

Neo

nate

s76

3442

4476

E co

li K

pne

umon

iae

KSD

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Hua

ng e

t al

2007

24Ch

ina

Jan

2000

ndashDec

20

02Co

hort

3 ye

ars

Hos

pita

lN

osoc

omia

l in

fect

ion

Vario

usN

eona

tes

3922

1756

2358

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nN

CCLS

200

0

Jain

amp M

onda

l 200

725b

Indi

aJa

n 20

04ndashD

ec

2005

Coho

rt2

year

sH

ospi

tal

Seps

isBl

ood

Neo

nate

s10

058

4258

2995

K p

neum

onia

e En

tero

bact

er sp

pD

oubl

e di

sk

diffu

sion

NCC

LS 2

003

Kuo

et a

l 20

0726

Taiw

an C

hina

Jan

2000

ndashOct

20

05Ca

sendashc

ontro

l5

year

s 9

mon

ths

Hos

pita

lVa

rious

Vario

usBi

rth

to N

S10

854

5428

274

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

NCC

LS 2

001

Lee

et a

l 20

0727

Repu

blic

of

Kore

aJa

n 19

99ndashD

ec

2005

Coho

rt7

year

sH

ospi

tal

Vario

usVa

rious

NS

228

3554

2925

2E

coli

K p

neum

onia

e D

oubl

e di

sk sy

nerg

y te

st V

itek-

GNI c

ard

CLSI

200

5

Sehg

al e

t al

2007

28In

dia

April

200

2ndashM

ay

2003

Coho

rt1

year

Hos

pita

lSe

psis

Bloo

dN

eona

tes

7538

2561

75M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

NCC

LS 2

002

Bhat

tach

arje

e et

al

2008

29b

Indi

a14

mon

ths

Coho

rt1

year

2

mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

243

2658

3224

3M

ultip

le sp

ecie

saD

oubl

e di

sk

diffu

sion

CLSI

200

8

Anan

dan

et a

l 20

0930

bIn

dia

Jan

2003

ndashDec

20

07Co

hort

5 ye

ars

Hos

pita

lSe

psis

Bloo

dN

eona

tes

9468

2672

8330

E co

li K

pne

umon

iae

Not

spec

ifyCL

SI 2

008

Kim

et a

l 20

0931

Repu

blic

of

Kore

aJa

n 20

04ndashA

pr

2009

Coho

rt5

year

s 2

mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

Child

ren

854

3283

1768

1E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

S

Shak

il et

al

2010

32In

dia

Jan

2006

ndashFeb

20

07Co

hort

1 ye

ars

Hos

pita

lVa

rious

Vario

usN

eona

tes

238

104

107

4446

9E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Gau

rav

et a

l 20

1133

Indi

aM

ay 2

007ndash

Apr

2008

Case

ndashcon

trol

1 ye

arH

ospi

tal

Seps

isBl

ood

Neo

nate

s34

450

5236

5116

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI d

ate

NS

Liu

et a

l 20

1134

Chin

aFe

b 20

09ndashJ

an

2011

Coho

rt2

year

sH

ospi

tal

Low

er re

spira

tory

tra

ct in

fect

ion

Sput

umlt

3 y

ears

242

9414

839

242

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

dat

e N

S

Wei

et a

l 20

1135

Chin

aJa

n 20

09ndashD

ec

2009

Obs

erva

tiona

l1

year

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

lt 1

yea

r27

214

412

853

1380

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

200

9

Min

ami e

t al

2012

36Ja

pan

July

201

1 (1

day

)Cr

oss-

sect

iona

l1

day

Hos

pita

lVa

rious

Rect

alle

12

year

s50

446

1262

Mul

tiple

spec

iesa

Dou

ble

disk

syne

rgy

test

CLSI

200

8

Zhen

g et

al

2012

37Ch

ina

2002

ndash200

8Co

hort

6 ye

ars

Hos

pita

lH

aem

atol

ogic

al

mal

igna

ncy

Bloo

dlt

16

year

s10

919

3852

3264

E co

li K

pne

umon

iae

Vite

k 60

syst

emN

CCLS

dat

e N

S

Vija

yaka

nthi

et a

l 20

1338

Indi

aD

ec 2

009ndash

Nov

20

10Co

hort

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tal

Seps

isVa

rious

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nate

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3917

150

Mul

tiple

spec

iesa

Dou

ble

disk

di

ffusio

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ate

NS

Fan

et a

l 201

439Ta

iwan

Chi

na20

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006

Case

ndashcon

trol

4 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

lt 1

5 ye

ars

312

104

208

3364

67E

coli

Dou

ble

disk

di

ffusio

nCL

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007

Them

phac

hana

et a

l 20

1440

Thai

land

Febndash

Sep

2013

Obs

erva

tiona

l8

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 2

1 ye

ars

166

8283

2616

6E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

201

2

Youn

g et

al

2014

41Si

ngap

ore

Nov

200

6ndashFe

b 20

07O

bser

vatio

nal

3 m

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mm

unity

Vario

usVa

rious

lt 2

1 ye

ars

1006

6912

44

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duci

ng

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roba

cter

iace

ae m

ethi

cilli

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sista

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taph

yloc

occu

s aur

eus

vanc

omyc

in-re

sista

nt E

nter

ococ

cus

spp

Dou

ble

disk

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ffusio

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007

Zuo

et a

l 20

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Chin

aJa

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ec 2

013

Obs

erva

tiona

l1

year

Hos

pita

lLo

wer

resp

irato

ry

tract

infe

ctio

nSp

utum

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mon

ths

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9394

7937

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coli

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neum

onia

e Ki

rby-

Baue

r disk

di

ffusio

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012

Duo

ng e

t al

2015

43Vi

et N

amJu

l 201

1ndashN

ov

2012

Coho

rt1

year

4

mon

ths

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nVa

rious

3 m

onth

sndash15

ye

ars

216

2217

5214

3E

coli

K p

neum

onia

e D

oubl

e di

sk

diffu

sion

CLSI

200

7

Han

et a

l 20

1517

cRe

publ

ic o

f Ko

rea

Apr 2

009ndash

Mar

20

13Co

hort

4 ye

ars

Hos

pita

lN

eutro

poen

ia

(febr

ile)

Bloo

dlt

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year

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2140

3461

E co

li K

pne

umon

iae

Vite

k 2

syst

emN

S

Han

et a

l 20

1544

dRe

publ

ic o

f Ko

rea

Jan

2010

ndashDec

20

14Co

hort

4 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

lt 1

8 ye

ars

205

2218

910

211

E co

li K

pne

umon

iae

Vite

k 2

syst

emN

S



Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

etho

dGu

idel

ines

use

d

ESBL

-po

sitiv

eES

BL-

nega

tive

Nish

a et

al

2015

45In

dia

Nov

201

2ndashJa

n 20

15Co

hort

3 ye

ars

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

le 1

8 ye

ars

385

159

226

4138

5E

coli

Kirb

y-Ba

uer d

isk

diffu

sion

CLSI

dat

e N

S

Agar

wal

et a

l 20

16 46

bIn

dia

2009

ndash201

2Co

hort

4 ye

ars

Hos

pita

lD

iarrh

oea

Stoo

lYo

ung

child

ren

6339

2398

1963

39E

coli

K p

neum

onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

SAm

ornc

haic

haro

ensu

k 2

01647

Thai

land

Jan

2010

ndashDec

20

14Co

hort

5 ye

ars

Hos

pita

lU

rinar

y tra

ct

infe

ctio

nU

rine

0ndash15

yea

rs11

719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

CLSI

dat

e N

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ma

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ths

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2001

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Man

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Figure 1

Table 2

Table 3

Figure 2

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Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6



Auth

orCo

untr

y or a

rea

Stud

y dat

esSt

udy d

esig

nSt

udy

dura

tion

Stud

y set

ting

Diag

nosis

Spec

imen

sit

eSa

mpl

e ag

esNo

of

child

ren

No o

f sam

ples

Prev

alen

ce

of ES

BL

infe

ctio

n

No o

f iso

late

s or

cultu

res

Bact

eria

l spe

cies

ESBL

det

ectio

n m

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dGu

idel

ines

use

d

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sitiv

eES

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2015

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Nov

201

2ndashJa

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15Co

hort

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ars

Com

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rinar

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ctio

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8 ye

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385

159

226

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5E

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Kirb

y-Ba

uer d

isk

diffu

sion

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dat

e N

S

Agar

wal

et a

l 20

16 46

bIn

dia

2009

ndash201

2Co

hort

4 ye

ars

Hos

pita

lD

iarrh

oea

Stoo

lYo

ung

child

ren

6339

2398

1963

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K p

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onia

e Vi

tek

2 sy

stem

CLSI

dat

e N

SAm

ornc

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ensu

k 2

01647

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land

Jan

2010

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20

14Co

hort

5 ye

ars

Hos

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lU

rinar

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ct

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ctio

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rine

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yea

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719

6916

117

E co

li K

pne

umon

iae

Hos

pita

l lab

orat

ory

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dat

e N

S

Shar

ma

et a

l 20

1648

Indi

aJa

n 20

13ndashA

ug

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Obs

erva

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year

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mon

ths

Hos

pita

lSe

psis

Bloo

dN

eona

tes

1449

101

6661

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Mul

tiple

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iesa

Dou

ble

disk

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rgy

test

NCC

LS d

ate

NS

Tsai

et a

l 20

1649

Taiw

an C

hina

Jan

2001

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20

12Ca

sendashc

ontro

l12

yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

eona

tes

350

7731

614

542

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tiple

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iesa

Dou

ble

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rgy

test

CLSI

201

2

Chen

et a

l 20

1750

Taiw

an C

hina

Jan

2004

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20

15Cr

oss-

sect

iona

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yea

rsH

ospi

tal

Bact

erae

mia

Bloo

dN

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tes

275

2219

27E

coli

Not

spec

ifyN

S

He

et a

l 20

1751

Chin

aM

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Jun

2016

Coho

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mon

ths

Hos

pita

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ry

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ctio

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utum

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ears

236

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nerg

y te

stCL

SI d

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Kim

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Repu

blic

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un

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Coho

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ths

Hos

pita

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ood

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ars

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4993

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5E

coli

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sk sy

nerg

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stN

CCLS

200

1

Man

dal e

t al

2017

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dia

Two

cons

ecut

ive

year

Coho

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year

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mm

unity

Dia

rrhoe

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ool

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E co

liM

odifi

ed K

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r disk

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usio

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ate

NS

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al

2017

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dia

Nov

201

2ndashM

ar

2016

Coho

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year

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mon

ths

Com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

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ye

ars

523

196

327

3852

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y-Ba

uer d

isk

diffu

sion

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201

0

Tsai

et a

l 20

1755

Taiw

an C

hina

2010

ndash201

4O

bser

vatio

nal

5 ye

ars

Hos

pita

lBa

cter

aem

iaBl

ood

lt 3

yea

rs41

1427

3441

E co

liN

SN

SBu

njou

ngm

anee

et a

l 20

1856

Thai

land

Jun

2016

ndashMay

20

17Ca

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ontro

l1

year

Hos

pita

l amp

com

mun

ityU

rinar

y tra

ct

infe

ctio

nU

rine

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onth

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ears

8040

4023

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coli

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neum

onia

e D

oubl

e di

sk

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sion

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0

Kita

gaw

a et

al

2018

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done

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Japa

nJa

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ov 2

014

Case

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trol

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arH

ospi

tal amp

co

mm

unity

Urin

ary

tract

in

fect

ion

Urin

e0ndash

15 y

ears

9437

1339

94E

coli

K p

neum

onia

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oubl

e di

sk

diffu

sion

CLSI

dat

e N

S

Wee

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ghe

et a

l 20

1858

Sri L

anka

Janndash

April

201

1Co

hort

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onth

sH

ospi

tal

Vario

usVa

rious

Neo

nate

s50

188

3650

E co

li K

pne

umon

iae

Dou

ble

disk

di

ffusio

nCL

SI amp

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C 2

011

CDC

Cen

ters

for D

iseas

e Co

ntro

l and

Pre

vent

ion

CLS

I Clin

ical

and

Lab

orat

ory

Stan

dard

s Ins

titut

e E

SBL

ext

ende

d-sp

ectru

m β

-lact

amas

e-pr

oduc

ing

bact

eria

NCC

LS N

atio

nal C

omm

ittee

for C

linic

al L

abor

ator

y St

anda

rds

NS

not

spec

ified

a M

ultip

le sp

ecie

s inc

lude

d Kl

ebsie

lla p

neum

onia

Esc

heric

hia

coli

Pseu

dom

onas

spp

Acin

etob

acte

r spp

Ent

erob

acte

r spp

and

Citr

obac

ter s

pp

b Stu

dies

with

dat

a on

ly o

n iso

late

s th

e re

mai

ning

stud

ies i

nclu

ded

data

on

patie

nts a

nd is

olat

es

c Neu

trpoe

nia

stud

yd U

rinar

y tra

ct in

fect

ion

stud

y

(

cont

inue

d)

Figure 1

Table 2

Table 3

Figure 2

Figure 3

Figure 4

Figure 5

Table 4

Table 5

Table 6

Figure 6

available evidence of antibiotic resistance from extended ... · extended-spectrum β-lactamases...

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