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84 Extended-spectrum beta-lactamase (ESBL)-producers and piperacillin/tazobactam in the era of lowered break-points and no confirmatory tests

Saturday, April 2, 2011
Trinity Ballroom (Hilton Anatole)
Jason M. Pogue, PharmD , Detroit Medical Center, Wayne State University, Detroit, MI
Dror Marchaim, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Paul R. Lephart, PhD , Detroit Medical Center, Wayne State University, Detroit, MI
Ryan P. Mynatt, PharmD , Detroit Medical Center, Wayne State University, Detroit, MI
Jing J. Zhao, PharmD , Detroit Medical Center, Wayne State University, Detroit, MI
Suchitha Bheemreddy, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Bharath Sunkara, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Judy Moshos, MT , Detroit Medical Center, Wayne State University, Detroit, MI
Kayoko Hayakawa, MD, PhD , Detroit Medical Center, Wayne State University, Detroit, MI
Teena Chopra, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Sorabh Dhar, MD , Detroit Medical Center, Wayne State University, Detroit, MI
Keith S. Kaye, MD, MPH , Detroit Medical Center, Wayne State University, Detroit, MI

Background: Until recently, the Clinical and Laboratory Standards Institutes (CLSI) had recommended that all isolates that tested ESBL positive be reported as resistant to penicillins, cephalosporins, and monobactams. Recently, CLSI has adopted lower breakpoints for most cephalosporins and no longer recommends ESBL testing for treatment purposes. Implementation of these new testing guidelines might lead to higher rates of organisms, notably ESBL-producers, being reported as susceptible to piperacillin/tazobactam.

Objective: The primary aim of this study was to analyze the susceptibility pattern of piperacillin/tazobactam in ESBL-producing organisms and evaluate the impact that new testing guidelines will have on patient therapy.

Methods: This study was conducted at the Detroit Medical Center (DMC), an 8-hospital healthcare system with over 2,200 inpatient beds. All unique patients ESBL positive cultures of Escherichia coli and Klebsiella pneumoniae from 2009 were analyzed. Species identification, susceptibility testing for piperacillin/tazobactam, and ESBL tests were all conducted via automated broth microdilution system Microscan® (Siemens; Germany), as part of routine testing according to the older CLSI criteria.

Results: There were 659 E. coli and 552 K. pneumoniae ESBL positive organisms at DMC during the study period. The Table displays the susceptibility pattern to piperacillin/tazobactam. In E. coli, 95% of ESBL-producing strains tested susceptible by current breakpoints (MIC50 ≤ 8; MIC90 ≤ 32); while 38% of K. pneumoniae tested as susceptible (MIC50 ≥ 128; MIC90 ≥ 128).

Conclusions: Most E. coli ESBLs and a large portion of K. pneumoniae ESBLs test as susceptible to piperacillin/tazobactam by current recommended breakpoints. The lack of ESBL confirmatory testing will lead clinicians to perceive this agent as a reasonable option in patients infected with ESBL producing organisms despite a lack of good efficacy data, and it's inferiority versus other agents (e.g. carbapenems) in comparative trials.

Table: Susceptibility ranges of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae

 

Piperacillin/tazobactam MIC (µg/mL)

 

≤ 8

16

32

64

≥128

E.coli

527 (80%)

53 (8%)

20 (3%)

26 (4%)

33 (5%)

K.pneumoniae

116 (21%)

28 (5%)

11 (2%)

55 (10%)

332 (62%)