mnh chanoine bacterial infection in cirrhosis cairo 2008

8/8/2019 MNH Chanoine Bacterial Infection in Cirrhosis Cairo 2008

http://slidepdf.com/reader/full/mnh-chanoine-bacterial-infection-in-cirrhosis-cairo-2008 1/32

Bacterial Infection in Liver Cirrhosis:the Microbiologist Point of View

Prof. Marie-Hélène NICOLAS-CHANOINE



Bacterial infections

life-threatening complications in cirrhotic patientsand common



30 to 5 0 % of hospitalized cirrhotic patients are concerned by bacterialinfections



Spontaneous Bacterial Peritonitis (SBP)

(± bacteremia)

Urinary Tract Infection (UTI)(± bacteremia)

Pulmonaryinfection

Others(peritoneal

tuberculosis )

25 % of deathdirectly due to

bacterialinfection



Host risk factors for SBP

Surviving to a previous SBP episodeLow ascitic fluid protein levels (<1 0 g/L)Gastrointestinal hemorrhage



Physiopathology of SBP

SBP is caused by intestinal micro-organismsthat translocate through the mucosal barrier tothe mesenteric lymph nodes , enter the

bloodstream and reach the ascitic fluid.



Parameter Number (%)

Community Nosocomial Total

Episode number 128 69 197

Isolate number 1 30 74 2 0 4

Plurimicrobial 2 5 7 (3.5) Enterobacteriacae 67 4 3 110

E.coli 61 (47) 27 (3 6 ) 88 (43) K lebsiella spp 2 6 8

Others 4 1 0 14

S treptococci 52 (40) 1 5 (20) 6 7 (32)Viridans group 27 11 3 8

S . bovis 9 2 11

Pneumococci 7 2 9

B group 8 0 8

S . aureus 2 5 7

Enterococcus spp 1 5 6 (3)Others 7 3 10

C andida 2 3 5 (2.5)

Bacterial species isolated from AF obtained from patients

with SBP and hospitalized in Beaujon hospital ( 199 8-2007)



Are bacterial factors involved in morbidityor/and mortality in cirrhotic patients withSBP?

³Genetic background of Escherichia coli isolatesfrom patients with spontaneous bacterial peritonitis:relationship with host factors and prognosis´.

F. Bert et al, Clin. Microbiol. Infect. (in press)



- 4 phylogenetic groups: A, B1, B2 and D

- extraintestinal pathogens: more often group B2isolates

- virulence factors (VF)-encoding genes

- group B2 isolates have more VF genes thannon B2 group isolates

Population structure of E. coli



VF gene Prevalence of VF gene, No. (%) of isolates

Group A(n=2 0 )

Group B1(n= 3 )

Group B2(n= 3 5)

Group D(n=18)

Total(n=76)

Adhesins

pap C 7 ( 3 5) 0 26 (74) 6 ( 33 ) 3 9 (51)

pap G allele II 0 0 15 (4 3 ) 6 ( 33 ) 21 (28)

pap G allele III 0 0 11 ( 3 1) 0 11 (14)

sfa/foc 0 0 18 (51) 0 18 (24)

Toxins

hly 0 0 18 (51) 1 (5.6) 19 (25)

cnf 1 0 0 17 (49) 0 17 (22)

Siderophores

fyuA 8 (4 0 ) 1 ( 33 ) 3 5 (1 00 ) 11 (61) 55 (72)

aer 10 (50 ) 2 (66) 19 (54) 12 (67) 4 3 (56)

Prevalence of virulence factor (VF) genes according to phylogeneticgroups in 76 E. coli isolates from patients with SBP (1998-2 00 5)

Mean VF score of B2 versus non B2: 15.4 vs 7. 3 p<1 0 -4



Value in the indicated group*

Variable Patients with B2isolates (n= 3 5)

Patients with non-B2isolates (n= 41)

PP

Age (year) 55 55 NS

Male gender 26 (75) 3 4 (8 3 ) NS

Alcoholism 22 (65) 25 (64) NS

Viral hepatitis 8 (24) 11 (28) NS

Hepatocellular carcinoma 7 (2 0 ) 4 (1 0 ) NS

Previous SBP episode 2 (6) 12 ( 30 ) 0 .0 15 3

Norfloxacin prophylaxis 1 ( 3 ) 9 (22) 0 .0 172

MELD score 26 29 0 .195 3

Blood neutrophils (cells/mm 3 ) 10 ,752 7,9 3 1 NS

Platelet (cells/m 3 ) 13 6,828 1 00 ,0 49 0 .0 82 3

Prothrombin ratio (%) 4 0 33 0 .0 558

Serum bilirubin ( mol/L) 2 00 178 NS

Serum creatinine ( mol/L) 142 182 NS

Serum sodium ( mol/L) 1 3 1 13 2 NS

AF neutrophils (cells/mm 3 ) 4,3 89 4,5 0 1 NS

AF protein (g/L) 11 1 0 0 .11 00

Hospital-acquired SBP 11 ( 3 1) 16 ( 3 9) NS

Positive blood cultures 9 (26) 15 ( 3 7) 0 .1487

Comparison of host factors in patients with B2 isolates and thosewith non-B2 isolates.

* data are no (%) of patients or mean value ; NS, non significant (p 0 .2) ; SBP, spontaneous bacterial peritonitisAF, ascitic fluid, red indicates host factors independently associated with non-B2 isolates



Overall, we found that the prevalence

of non B2 isolates (fewer VF andmore often resistant) increased withthe severity of liver disease



Variable OR CI 95 % P

MELD score 1.8 3 2 1.29 2.59 0 .000 7

Hospital-acquiredSBP

4.1 3 1.2 0 14.21 0 .0 247

Prothrombin ratio 1.51 3 1.0 2 14. 0 5 0 .0 412

Serum creatininelevel

1.77 4 1.1 3 2.78 0 .0 127

Hospital-acquiredSBP

4.0 4 1.16 14. 0 5 0 .0 281

Multiple logistic regression of risk factors for in-hospitalmortality 1

1: the first multivariate analysis tested the MELD score and the second multivariateanalysis tested the components of the score, 2: value for an increase of 5, 3 : value for adecrease of 1 0 %, 4: value for an increase of 5 0 mol/L



Host factors, namely the severity of renal and hepatic dysfunctionsoutweigh bacterial factors in

predicting SBP in-hospital mortality



Viridans S treptococci



Viridans group streptococci (VGS) in 56 episodes*of SBP and/or bacteremia in 51 patients** (1998-2 00 6)

Species SBP(n = 3 9)***

Bacteremia withoutSBP (n = 17)

S . oralis 14 6S . mitis 10 1S . salivarius 4 6S . gordonii 3 3

S . sanguis 3 0

S . vestibularis

3 0

S . mutans 0 1

others 2 0

* 60 ,7 % acquired in the community,** 5 patients with 2 consecutive episodes*** 4 episodes with bacteremia

Liver Transplantation (in press)



Antibiotic susceptibility

of the 56 VGS

Ten patients had a prior episode of SBP andwere receivingnorflaxacin prophylaxis.

No VGS resistant tofluoroquinolones .

penicillin: 71 %amoxicillin: 87.5 %cefotaxime: 89. 3 %erythromycin: 59 %levofloxacin: 1 00 %moxifloxacin: 1 00 %



Demographic and biological data in 115 episodes of SBPcaused by viridans group streptococci or E. coli

VariableSBP caused by

pVGS (n = 3 9) E. coli (n = 76)

Age (year) 59. 3 54.7 NS

Male gender 30 (76.9 %) 6 0 (78.9 %) NS

Alcoholism 18 (46.2 %) 46 (6 3 %) NS

Viral hepatitis 17 (4 3 .6 %) 19 ( 3 6 %) NS

Carcinoma 7 (17.8 %) 11 (14.5 %) NS

MELD score 19.5 27.9 < 0 .0 1

Norfloxacin prophylaxis 9 (2 3 .1 %) 1 0 (13 .2 %) NS

Blood PMN (cells/mm 3 ) 7,672 8,85 0 NS

AF PMN (cells/mm3

) 1,426 4,451 < 0 .00 1AF protein (g/L) 9.2 1 0 .4 NS

Nosocomial origin 1 3 (33 .3 %) 24 ( 3 1.6 %) NS

Positive blood cultures 4 (1 0 .5 %) 29 ( 3 5.5 %) < 0 .0 1

15-day mortality 9 (2 3 .1 %) 27 ( 3 8 %)* NS NS, non significant; PMN, polymorphonuclear leucocytes; AF, ascitic fluid.* Data available for 71 patients.



Multi drug-resistance in E. coli

related to extended-spectrumß-lactamase (ESBL) production,notably CTX-M enzymes



Endémic CTX-M-1 CTX-M-8 CTX-M-9Sporadic CTX-M-2

2005

CTX-M-2, -5

CTX-M-16, -17

CTX-M-8

CTX-M-9, -16

CTX-M-1, 3, 15

CTX-M-9, -14, 18, 19, 20, 21

CTX-M-2, -5

CTX-M-, 3, 15

CTX-M-2

TOHO-like

CTX-M-2

CTX-M-3, 15

CTX-M-14

CTX-M-3, 15

CTX-M-9, -13, -14

CTX-M-3

CTX-M-3

CTX-M-9,-14

CTX-M-1,10,15

CTX-M-4, -6

CTX-M-3

CTX-M-15

CTX-M-9,-14

CTX-M-1,10,15,32

L ewis J, AAC 2007, « CTX-M-type as the predominant ESB L isolated in a US health

care system » (dominance of CTX-M- 1 5)

Canton R. Curr. Opin. Microbial. 2 00 6



Groupe B2Resistance to fluoroquinolonesLower number of VF-encoding genes than expected in B2 isolates



Canada

France

Spain

England

Turkey

India

Portugal

Switzerland

Korea



ESBL-producing E.coli and cirrhotic patients ?

Still rare as agent responsible for SBP / bacteremia

- 2 patients, June and Sept 2 00 7 at Beaujon hospital- Korean J Hepatol sept 2 00 7: survey on 12 years,

emergence of ESBL-producing E. coli

but carried in the digestive tract (rectal swabs)



Period Incidence / 1 00 screened patients

Hepatology* ICU** Hospital

7/2 6/ 3 3 .75 4.7

15/6 15/12 4 2

Beaujon Hospital (2 00 6): incidence of fecalESBL-positive enterobacteriaceae

* patients screened at admission,** patients screened at admission, then once a week

8 patients with ESBL-producing E. coli, 5 CTX-M-15 and 2 isolates belonging to clone ST1 3 1



In 2 00 8Good and bad news about clinical andmicrobiological data with regard to SBP

Good news: norfloxacin prophylaxis not only

decreases the risk of second SBP but also delayshepato-renal syndrome and improves survival incirrhosis. Fernandez J et al, Gastroenterology. 2 00 7 Sep;1 33 (3 ):818-24.

Bad news. E. coli is become the enterobacterialspecies the most concerned by ESBL andfluoroquinolone resistance is extremely frequent in

those E. coli producing CTX-M enzyme



Frederic Bert: infection in cirrhotic patients and patientswith liver transplant

Véronique Leflon Guibout: molecular mechanisms of resistance

and molecular epidemiology

Latifa Noussair: M ycobacterium tuberculosis infection diagnosisincluding tuberculosis peritonitis in cirrhotic patients



Characteristic Value*

Epidemiological featuresAge (yr) 54.7 ± 1 0 .6

Male gender 6 0 (78.9)

Alcoholism 46 (6 3 )

Viral Hepatitis 19 ( 3 6)

Carcinoma 11 (14.5)

Previous SBP episode 14 (18.4) Norfloxacin prophylaxis 1 0 (13 .2)

Meld score 27.9 ± 9.7

Blood variables

PMN (cells/mm 3 ) 8,85 0 ± 5,989

Platelet (cells/mm 3 ) 117, 000 ± 85,618

Prothrombin ratio (%)3

5.9 ± 15.6Bilirubin (µmol/L) 188 ± 1 3 8

Creatinine (µmol/L) 16 3 ± 14 0

Sodium (mmol/L) 1 3 1 ± 5.6

Ascitic fluid variables

PMN (cells/mm 3 ) 4,451 ± 4,72 0

Total protein (g/L) 1 0 .4 ± 5.1

Characteristics of cirrhotic patients in 7 6

episodes of spontaneous bacterial peritonitis(SBP)

* Data are means ± SD or numbers (%) of patients



Prevalence of group or VF gene, no. (%)

TraitCiprofloxacin-susceptible

(n= 64)Ciprofloxacin-resistant

(n=12)

Phylogenetic group

A 1 3 (20 .3 ) 7 (58. 3 )

B1 2 ( 3 .1) 1 (8. 3 )

B23

5 (54.7)0

D 14 (21.9) 4 ( 33 .3 )

VF genes

pap C 3 4 (5 3 .1) 5 (41.7)

pap GII 21 ( 3 2.8) 0

pap GIII 11 (17.2) 0

sfa/foc 18 (28.1) 0

hly 19 ( 29.7) 0

cnf 1 17 (26.6) 0

fyuA 49 (76.6) 6 (5 0 )

aer 3 6 (56.2) 7 (58. 3 )

Distribution of phylogenetic groups and virulence factor (VF)genes in relation to susceptibility to ciprofloxacin



Value in the indicated group*

Variable Patients who died (n= 3 8) Patients who survived (n= 33 ) P

Age (year) 51.7 5 3 NS

Male gender 3 1 (81.6) 25 (75.7) NS

Alcoholism 21 (58. 3 ) 22 (68.7) NS

Viral hepatitis 1 0 (27.8) 8 (25) NS

Hepatocellular carcinoma 6 (15.8) 5 (15.1) NS

Previous SBP episode 5 (1 3 .2) 8 (24.2) NS

Norfloxacin prophylaxis 3 (7.9) 6 (18.2) NS

MELD score 3 1.6 2 3 .1 0 .00 12

Blood neutrophils (cells/mm 3) 10 ,29 3 7,85 0 0 .116 3

Platelet (cells/m 3) 117,552 114,18 0 NS

Prothrombin ratio (%)3

1.1 42.20

.00

48Serum bilirubin ( mol/L) 227.2 15 3 .3 0 .03 57

Serum creatinine ( mol/L) 2 0 1.7 112.6 0 .0 93

Serum sodium ( mol/L) 1 30 .9 1 3 1.9 NS

AF neutrophils (cells/mm 3) 4,992 4,181 NS

AF protein (g/L) 1 0 .4 9.7 NS

B2 group 16 (48.1) 17 (51.5) NS

VF score 2.9 2.9 NS

Amoxicillin resistance 21 (55. 3 ) 14 (42.4) NS

Amoxi-clavulanate resistance 5 (1 3 .2) 5 (15.1) NS

Cefatoxime resistance 1 (2.6) 1 ( 3 ) NS

Ciprofloxacin resistance 5 (1 3 .2) 6 (18.2) NS

Cotrimoxazole resistance 14 ( 3 6.8) 7 (21.2) 0 .1542

Hospital-acquired SBP 16 (42.1) 7 (21.2) 0 .00 65

Positive blood cultures 16 (42.1) 8 (24.2) 0 .1161

Appropriate empiric antibiotics 33 (94. 3 ) 30 (96.7) NS

Albumin therapy 9 (2 3 .7) 11 ( 33 .3 ) NS

Unvariate analysis of host and bacterial factors associated with in-hospital mortality

* data are no (%) of patients or mean value ; NS, non significant (p 0 .2) ; SBP, spontaneous bacterial peritonitis ; AF, ascite fluid ; VF, virulence factor



Bacteremia without SBP (n = 17)*Ascite Number

without 3

Sterile ascite 9

Bacterascites (PNM < 25 0 mm 3 ) 5* one patient with endocardites

@ primary bacteremia = 16

mnh chanoine bacterial infection in cirrhosis cairo 2008

Documents