ESBL
Jasmin Fauteux
March 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
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Ampicillin
Ceftriaxone
Pip/tazo
Cipro
Nitrofurantoin
TMP/SMX
Disposition?
R
R
S
R
S
S
Goals
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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
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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 Sensitivity
ESBL
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
12,8%
4,7%
26,6%
13,9%
54,9%
12,9%
45,5%
25,9%
Klebsiella
E. Coli
33,8%
32,4%
35,5%
26,3%
Canada
ESBL
Amp C
E. Coli
4,4%
*2,6%
K. Pneumoniae
1,3%
Pseudomonas
7,2%
CANWARD 2008
*CANWARD 2007-2009
Carbapenem R
5,6%
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
E. Coli
ACH
PLC
FMC
RGH
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
Klebsiella species
ACH
PLC
FMC
RGH
95%
94%
97%
98%
Calgary P. aeruginosa
• 2008-2010 Antibiograms
ACH
PLC
FMC
RGH
Ceftazidime
93%
94%
87%
96%
Meropenem
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94%
91%
90%
Risk
Factors
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
12,8%
4,7%
26,6%
13,9%
54,9%
12,9%
45,5%
25,9%
Klebsiella
E. Coli
33,8%
32,4%
35,5%
26,3%
- 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 infections
Treatment
• Even with In Vitro susceptibility, we should not use:
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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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