ESBL and CPE: Mutants,

Migrants and Masterminds

Debbie Demizio BA RRT CIC

IPAC-CSO Education Day

May 8, 2014

Objectives

MUTANTS

• Describe the characteristics of ESBL and CPE

• Compare the threat of ESBL and CPE

MIGRANTS

• Identify the risk factors

• Consider travel as a risk factor

MASTERMINDS

• Identify infection control measures

• State the criteria to discontinue contact

precautions

• Select the appropriate tests for surveillance

• Be aware of the important role of antibiotic

stewardship

2

Antibiotic resistance

3 Image source: Conly J. CMAJ 2002

4

Fluoroquinolone use and correlation to ciprofloxacin

resistance among uropathogens in British Columbia

5 Patrick & Hutchinson, CMAJ 2009

Definitions

• β-lactam antibiotics – Penicillins

– Cephalosporins

• β-lactamase – Enzymes produced by certain bacteria that

render the above antibiotics ineffective

– First detected in E. coli in 1962

6

Image Source: PHO

7

Image source: CDC

“A serious threat is defined as, a significant

antibiotic-resistant threat. These threats are not

considered urgent, but are expected to worsen

and may become urgent without ongoing public

health monitoring and prevention activities.”

ESBL

Extended spectrum β lactamase

– Not an organism, but describes the characteristic of some gram negative bacteria; most commonly

• E. coli (1962)

• Klebsiella pneumoniae (1983)

• Others

8 Image source: Microbewiki.kenyon.edu

Characteristics of ESBLs

• Gram negative rods

• Resistance to β lactam antibiotics:

– All Penicillins

– Cephalosporins

• Sensitive to:

– Cephamycins

– Carbapenems

9

Image source: CDC

Why ESBL is a concern

1. Difficult to treat infections

2. The ability to produce β-lactamase can transfer to

other strains and species of bacteria

3. Can be difficult to detect by routine susceptibility

tests, causing delay in treatment with an

appropriate antibiotic

4. Longer hospital stays, increased cost of care

5. Increased risk of death

6. Outbreaks are possible and can be difficult to

control, especially in long term/chronic care

10

Risk factors for ESBL infection

Acute care

• Increased length of stay

• ICU – invasive devices – Catheters

– Feeding tubes

– Trach

• Antibiotics

Chronic care

• Poor functional status

• Urinary catheters

• Recent/recurrent antibiotic use

• Diabetes

11

All provide opportunities for transmission

Travel is a risk factor for ESBL Tangden et al. 2010

• A prospective pre-post travel

• Sweden, over a 15-month period (<2008)

• n = 100

• Most were vacationers (89%)

• Median length of stay was 2 weeks

• 24% of international travellers became colonized with ESBL producing bacteria

• 9% were still positive after 6 months

• Travellers’ diarrhea was a statistically significant risk factor

12

Travel is a risk factor for ESBL Tangden et al. 2010

13

0

10

20

30

40

50

60

70

80

90

100

India Asia MiddleEast

SouthernEurope

Africa NorthAmerica

SouthAmerica

Percentage of travellers who became colonized with ESBL

Travel is a risk factor for ESBL Paltansing et al. 2013

• Prospective cohort study, pre-post travel

• n = 370, March – September, 2011

• 113 (31%) colonized with ESBL post travel

– 19 (17%) still colonized after 6 months

• Household contacts

– 11 contacts of 4 ESBL positive travellers

– 2 (18.1%) ESBL positive

14

Duration of ESBL colonization

15

• n = 1,884 patients

• 40% were persistent carriers

• Median time to clear was 6.6 months

(Range 3.4 – 13.4 months)

CPE

ESBL’S MUTANT “EVIL COUSIN”

16

Image source: CDC

17 Image source: CDC

“These are high-consequence antibiotic-resistant

threats because of significant risks identified

across several criteria. These threats may not be

currently widespread, but have the potential to

become so and require urgent public health

attention to identify infections and to limit

transmission.”

Definitions

• Carbapenem antibiotics – Imipenem

– Meropenem

– Ertapenem

– Dorapenem

• Carbapenemase – Enzyme produced by certain bacteria that

render the above antibiotics ineffective

18

Image source: PHO

CRE / CPE

• Gram negative bacteria

• Carbapenem-resistant enterobacteriae (CRE) or

Carbapenemase-producing enterobacteriae (CPE)

• Resistant to carbapenems and 3rd generation

cephalosporins

• Types

– Serine based

• IMP – Japan, 1987

• VIM – Verona Italy, 1999

• KPC – North Carolina, 1996

– Zinc based (metallo β lactamase)

• New Delhi NDM-1, 2009

• Treatment options – Colistin, Tigecycline 19

Image source: CDC

Why CPE is a concern

• Very limited therapeutic options

• 40-50% mortality rate

• Can spread

20

Image source: CDC.org

Risk factors for CPE

• Male

• > 60 yrs old

• Hospitalized within past 12 months

• Hospitalized outside Canada

• Chronic medical conditions

– End stage renal disease

– Cancer/chemotherapy

21 Image source: CDC

Is travel is a risk factor for CPE? Paltansing et al. 2013

• Prospective cohort study, pre-post travel

• n = 370

• 0 (0%) colonized with CPE post travel

22

Is travel is a risk factor for CPE? Peirano et al. 2014

Alberta, 2010-2013

n = 12 patients

– healthcare encounters outside Canada

– Most had UTIs

– 1 case of spread resulting in death

17 strains of CPE

Conclusion:

“Clinical microbiology labs should remain vigilant in detecting bacteria with carbapenemases”.

23

NDM-1

• Associated with “medical tourism”

• Now found in 26

countries worldwide

24

Image source: Globe and Mail

NDM-1

“We estimate that the carriage of NDM-1 in

India is between 100 and 200 million”

- The Times of India, Oct 9, 2011

25

26

Prevalence of CPE in Ontario

27

CPE positive isolates by LHIN, April 2008 to Dec 2012 Health Ontario

Public Health Ontario, CPE surveillance report, Vol. 1 Issue 4, April 2013

CPE by type

28

Duration of colonization

• Follow up screening (rectal swabs) of 97/137 CRE patients post-discharge

• Time to clear – mean 387 days (95% CI; 312-463)

29

Infection Prevention & Control

30

Prevention strategies

1. Hand hygiene

2. Contact precautions

3. Cohorting

4. Minimize use of invasive devices

5. Promote antibiotic stewardship

6. Screening

31 Image source: PHO stock

Accommodation and precautions

• Private or cohorted with like

• Contact precautions • Dedicated

toilet/commode • Dedicated equipment

– Wheelchair – IV pump – Feeding pump – BP cuff – Stethoscope

• Remove catheters if possible

32

Image source: PHO RICN

Criteria to discontinue contact

precautions (PIDAC)

ESBL

• ESBL infection is resolved

AND

• Cleared of carrier status

– Screen for ESBL x 3, at least one week apart; not on Abx

AND

• Consultation with Infection Prevention and Control

CPE

• Maintain precautions

for the duration of

hospitalization

33

Image source: PHO RICN

Surveillance

• Admission screening is targeted to at risk patients only because ESBL and CPE are not endemic in this region

• CPE is a critical result

• In the event of a new Healthcare Associated Infection (HAI) case conduct point prevalence

• Screen known carriers, room-mates, outbreak exposed

• Colonization is possible, so patient may be capable of transmission (direct/indirect)

34

Risk-factor based admission

screening for ESBL and CPE Questions Screening

Positive for ESBL? Specimens for ESBL screening • Fecally stained rectal

swab/stool • Urine for ESBL (sterile

container)

Positive for CPE? Has the patient received health care in another country in the previous 12 months? Is the patient a direct transfer from another healthcare facility outside Canada?

Specimens for CPE screening 1. Fecally stained rectal

swab/stool 2. Urine for CPE (sterile

container) 3. Swab wounds 4. Swab exit sites (critical care) 5. Endotracheal suction

(critical care)

35 Adapted from PIDAC Annex A, page 48

Resources

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Conclusions

• The prevalence of ESBL and CPE is increasing

• History of travel outside North America or

hospitalization out of country is an important part

of the risk assessment for ESBL and CPE

• Active surveillance is required for those at risk

• Laboratory testing and notification of results is

necessary

• Transmission should be prevented with

consistent use of routine practices

• Colonization takes a very long time to clear

• Infection prevention & control and Antibiotic

stewardship play key roles

37

“To avoid taking action to

resolve antimicrobial resistance

is to commit Canadians to the

perils of living in the pre-

antibiotic era” - Canadian Committee on Antibiotic Resistance

38 Image source: www.delpiano.com

References Birgand G, Armand-Lefebvre L, Lolom I, Ruppe E, AndremontA, Lucet JC. Duration of colonization of

extended-spectrum beta-lactamase producing enterobacteriaceae after hospital discharge. American Journal of Infection Control. 2013; 41: 443-7.

Boucher HW et al. Bad drugs, no drugs: No ESKAPE! Clin. Infect. Dis.2009; 48(1): 1-12.

Centers for Disease Control. CPE guidance for control of CPE. C2012. Available from http://www.cdc.gov/hai/pdfs/cre/CRE-guidance-508.pdf

Centers for Disease Control. 2013. Antibiotic resistance threats within the United States. Available from http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf

Centers for Disease Control. Get smart for healthcare: Inpatient stewardship. Available from http://www.cdc.gov/getsmart/healthcare/inpatient-stewardship.html#Facts

Centers for Disease Control. Vital signs. C2013. Available from http://www.cdc.gov/vitalsigns/HAI/CRE/infographic.html

Conly J. Antimicrobial resistance in Canada. CMAJ 2002; 167(8): 885-91.

Conly J, Pitout J, Dalton B, Sabuda D. National Collaborating Centre for Infectious Diseases. The W-5 of NDM-1: the pinnacle of antimicrobial resistance. Nov 2011. Available from http://www.nccid.ca/files/Purple_Paper_Note_mauve/PP_33_EN.pdf

Johnson SW, Anderson DJ, May DB, Drew RH. Utility of a clinical risk factor scoring model in predicting infection with ESBL-producing Enterobacteriaceae on hospital admission. ICHE, April 2013

Paltansing S, Vlot A, Kraakman MEM, Mesman R, et al. Extended-Spectrum β-Lactamase producing Enterobacteriaceae among travellers in the Netherlands. Emerging Infectious Diseases. 2013; 19:8. Available from http://wwwnc.cdc.gov/eid/article/19/8/13-0257_intro.htm

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References – con’t Patrick DM, Hutchinson J. Antibiotic use and population ecology: How you can reduce your “resistance

footprint”. CMAJ 2009; 180(4): 416-421.

Peirano G, Ahmed-Bentley J, Fuller J, Rublin JE, Pitout JD. 2014. Travel-related carbapenemase- producing Gram negatives in Alberta, Canada: the first three years. 2014. J. Clin. Microbiol.

PIDAC. Routine Practices and Additional Precautions, Annex A, Feb 2012. Available from http://www.oahpp.ca/resources/documents/pidac/Annex%20A%20-%20PHO%20template%20-%20REVISION%20-%202012Apr25.pdf

Public Health England. Acute trust toolkit for the early detection, management and control of

Carbapenemase-producing Enterobacteriaceae. 2013. Available from

http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317140378646

Public Health Ontario. Quarterly CPE surveillance report, April 2013. Available from http://www.publichealthontario.ca/en/DataAndAnalytics/Documents/CPE_Quarterly_Surveillance_Report_2013_06.pdf

Public Health Ontario. Quarterly CPE surveillance report, October 2013. Available from http://www.publichealthontario.ca/en/DataAndAnalytics/Documents/Carbapenemase_producing_enterobacteriaceae_(CPE)_surveillance_report_October_2013.pdf

Tangden T, Cars O, Melhus A, Lowdin E. 2010. Foreign travel is a major risk facto for colonization with

Escherichia coli producing CTX-M type Extended-Spectrum β-Lactamases: a prospective study with

Swedish volunteers. Anitmicrobial Agents and Chemotherapy;54:9;3564-3568.

Walsh TR, Weeks J, Livermore DM, Toleman MA, Dissemination of NDM-1 positive bacteria in the New Delhi

environment and its implications on human health. The Lancet Infect. Dis. 2011; 11(5): 355-62.

Zimmerman RS, Assous MV, Bdolah-Abram T, Lachish T, Yinnom AN, Wiener-Well Y. Duration of

carriage of carbapenem-resistant Enterobacteriaceae following hospital carriage. AJIC 2013;

41:190-4.

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