ESBL Jasmin Fauteux March 29 th 2012. PLC Intake 66 yo female with dysuria and pelvic pain Just returned from visit to Pakistan VS Normal Physical exam:

ESBL

Jasmin FauteuxMarch 29th 2012

PLC Intake

• 66 yo female with dysuria and pelvic pain

• Just returned from visit to Pakistan

• VS Normal

• Physical exam: Mild right CVA tenderness

• Seen 2d ago and given Cipro for UTI

UA: WBC-21-30 Nitrites +

E. Coli > 8 x 106

• Ampicillin R• Ceftriaxone R• Pip/tazo S• Cipro R• Nitrofurantoin S• TMP/SMX S

Disposition?

Goals

• Definition• Microbiology• Incidence• Risk factors• Morbidity• Management• Prevention

A new problem?

• 1940s: First β-lactamase in E. coli

• 1980s: Introduction of Cefotaxime in Europe

• 1984: First reported case of ESBL in France and Germany

• 1988: First case in US

Definitions

• Beta-lactams– Beta-lactam ring that inhibits cell wall synthesis– Penicillins, cephalosporins, carbapenems and

monobactams

• Beta-lactamase– Bacterial enzymes that open the beta-lactam ring,

inactivating the antibiotic– Currently over 600 β-lactamases

Extended spectrum β-lactamase

• Activity against oxyimino-cephalosporins (3rd generation) and monobactams but not the cephamycins

• Inhibition by beta-lactam inhibitors

• AmpC– Resitant to cephamycins and beta-lactam inhibitors

• Carbapenemase– Resistant to carbapenems

Extended spectrum β-lactamase

• Heterogeneous group

• Testing of various oxyimino-β-lactams required

Which bugs?

• All Gram-negative bacterias– Klebsiella species– E. coli– Pseudomonas– Acinetobacter– Burkholderia– Citrobacter– Enterobacter– Morganella– Proteus– Salmonella– Serratia– Shigella

Detection

• 2010 CLSI– New MIC criterias

– Correlates with clinical outcome

CLSI SensitivityESBL Cefotaxime Ceftriaxone Cefpodoxime Ceftazidime Cefepime

Se 99,2% 99,2% 98,3% 65,3% 11,9%

Sp 40,7% 41,5% 44,9% 55,9% 99,2%

AmpC Cefotaxime Ceftriaxone Cefpodoxime Ceftazidime Cefepime

Se 100% 100% 100% 84,6% 7,7%

Sp 34,6% 41% 32,1% 39,7% 100%

• Any gram-negative bacteria

• Resistance to a single 3rd generation cephalosporin

KlebsiellaE. Coli

12,8% 4,7% 26,6%

13,9%

35,5%26,3%

45,5%25,9%

33,8%32,4%

54,9%12,9%

Canada

ESBL Amp C Carbapenem R

E. Coli 4,4% *2,6%K. Pneumoniae 1,3%Pseudomonas 7,2% 5,6%

CANWARD 2008*CANWARD 2007-2009

Calgary E. coli

Molecular Epidemiology over an 11-Year Period (2000 to 2010) of Extended-Spectrum -Lactamase-Producing Escherichia coli Causing Bacteremia in a Centralized Canadian Region, Peirano et al, Journal of Clinical microbiology

Calgary E. Coli

• 2008-2010 Antibiograms– Sensitivity to Ceftriaxone

ACH PLC FMC RGH

E. Coli 93% 87% 90% 87%

Calgary K. pneumoniae

Molecular epidemiology of extended-spectrum-b-lactamase-producing Klebsiella pneumoniae over a 10 year period in Calgary, Canada, Peirano, G. Journal of Clinical Microbiology

Calgary Klebsiella

• 2008-2010 Antibiograms– Sensitivity to Ceftriaxone

ACH PLC FMC RGH

Klebsiella species 95% 94% 97% 98%

Calgary P. aeruginosa

• 2008-2010 Antibiograms

ACH PLC FMC RGH

Ceftazidime 93% 94% 87% 96%

Meropenem - 94% 91% 90%

RiskFactors

Colonization is the main risk factor

Carrier

-24-33% still colonized at 6mo-10-12% still colonized at 3+ years

Prior antibiotic use CONSISTENTLY increases your risk

• All antibiotics

• 3rd generation cephalosporins– Restriction of use caused reduction in ESBL infection

88% of healthy travelers returning from India were colonized with ESBL E.coli

KlebsiellaE. Coli

12,8% 4,7% 26,6%

13,9%

35,5%26,3%

45,5%25,9%

33,8%32,4%

54,9%12,9%

- Hospital stay and contact- Health care workers contact- Long term care

Instrumentation

• Central or arterial line• Urinary catheter• Mechanical ventilation• G/J-tube• Hemodialysis

• Severity of illness

• Comorbidities

• Low birth weight (NICU)

Who cares?

Hospital cost and length of stay roughly double

-OR for mortality = 2,35-Adjusted for sepsis severity and with appropriate initial therapy = 1,37

Inappropriate therapy increases mortality by 2-10 fold

Back to our patient…

Management

• High bacterial inoculum

• Uncomplicated UTI

Everything but uncomplicated UTI

• Carbapenems–Need to speak to ID– Ertapenem 1g IV q 24hrs– In patient vs outpatient

Serious bacterial infectionsTreatment

• Even with In Vitro susceptibility, we should not use:

– 3rd generation cephalosporins– 4th generation cephalosporins*– Cephamycins– Pip/tazo– Fluoroquinolones– Aminoglycosides

* Might change with 2010 CLSI, potential future therapy

What if…

Speak to ID-Amikacin-Tigecycline-Colistin

Uncomplicated UTI

• If sensitive-Nitrofurantoin - 5 days-Fosfomycin* - 3g PO once

-Fluroquinolones – May be considered

*Not available in Canada

Prevention

• Isolation of ESBL

• Responsible antibiotic use

• Avoiding unnecessary procedures

Contact Isolation

• Reduces incidence of ESBL by 55%

• In Calgary: - no isolation- no screening

Antibiotic stewardship

• Use of narrower spectrum antibiotics– Avoiding cephalosporins and fluroquinolones

• Minimizing days of therapy

Avoid unnecessary procedures

Carbapenem resistance

Carbapenem resistance

• Pseudomonas: 3,3%• A. Baumannii: 2,7%• E. Coli & Klebsiella: 0,1%

• Mortality:40-60%

• Contact ID & contact isolation

Thanks to• Dr. Michael Parkins

• Dr. Shawn Dowling

Thank you!

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