Susceptibilities of ESBL-producing Enterobacteriaceae to ertapenem, meropenem and piperacillin-tazobactam with and without clavulanic acid.
BACKGROUND
Faced with the extended-spectrum beta-lactamase (ESBL) pandemic, we compared the susceptibilities of ESBL-producing Enterobacteriaceae to ertapenem, meropenem and piperacillin-tazobactam with and without clavulanate.


METHODS
121 strains of Escherichia coli and Klebsiella were studied. 70 strains were originally reported as resistant to ceftazidime based upon disk diffusion; 51 strains were originally reported as sensitive to ceftazidime based upon previous guidelines of the National Committee for Clinical Laboratory Standards, but subsequently shown to be ESBL producers. Minimal inhibitory concentrations (MICs) of the strains towards ertapenem, meropenem and piperacillin-tazobactam were determined by Etest. The effect of adding clavulanate on the MICs was determined by performing the Etest, using plates containing 2 microg/ml of clavulanate.


RESULTS
The MIC90 of all isolates was 0.094 and 0.25 microg/ml for ertapenem, 0.032 and 0.064 microg/ml for meropenem, and 16 and 256 microg/ml for piperacillin-tazobactam with and without clavulanate, respectively.


CONCLUSIONS
ESBL-producing organisms were more susceptible to meropenem than to ertapenem, although the MICs to ertapenem were well within clinically achievable levels. Piperacillin-tazobactam was ineffective in a large percentage of isolates. The presence of clavulanate resulted in a 5-fold decrease in the MIC of ertapenem and in a drastic reduction in the MIC of piperacillin-tazobactam. The decrease observed with ertapenem is unlikely to be of clinical significance. Thus, in our hospital, ertapenem could be a good meropenem-sparing agent for infections due to ESBL-producing organisms. Piperacillin-tazobactam appeared to be a poor choice, as our isolates produce ESBLs which are not successfully inhibited by tazobactam.
Raveh
David
D
Infectious Diseases Unit, Shaare-Zedek Medical Center, Jerusalem, Israel.
Yinnon
Amos M
AM
Broide
Ellen
E
Rudensky
Bernard
B
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019818:Clavulanic Acid / Q000494:pharmacology*; D004347:Drug Interactions; D000077727:Ertapenem; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D013845:Thienamycins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D019818:Clavulanic Acid; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000077731:Meropenem; D000077727:Ertapenem; D010878:Piperacillin