Effect of inoculum size of Enterobacteriaceae producing SHV and CTX-M extended-spectrum -lactamases on the susceptibility to -lactam combinations with inhibitors and carbapenems

Aim Many extended-spectrum β-lactamases (ESBL) producingisolates of E. coli and K. pneumoniae are susceptible in vitro toamoxycillin-clavulanate (AMC), ceftazidime-clavulanate (CAZ/cl), and piperacillin-tazobactam (TZP), but MICs increase substantiallywhen higher inoculum is applied. The aim of this studywas to determine the effect of inoculum size on the susceptibilityof E. coli and K. pneumoniae isolates with well characterized ESBLs,to amoxycillin (AMX), AMC - amoxycilin + clavulanate,ceftazidime (CAZ), CAZ/cl - ceftazidime + clavulanate, piperacillin(PIP), TZP - tazobactam + piperacilin, imipenem (IMI) andmeropenem (MEM).Methods Minimum inhibitory concentrations (MIC) were determinedby broth microdilution method using inocula that differed100 fold in density.Results Inoculum effect for CAZ/cl was detected in 52% of SHV-2producing K. pneumoniae strains followed by AMC (43%) andTZP (38%). SHV-5 producing K. pneumoniae strains showed themost pronounced inoculum effect with CAZ/cl and AMC and tolesser extent with TZP. Inoculum effect was observed for AMC,CAZ/cl and TZP in 71% of SHV-12 producers. E. coli producingSHV-5 β-lactamase showed the most pronounced inoculumeffect with AMC, followed by CAZ/cl and TZP. Strains producingCTX-M β-lactamases had a marked inoculum effect with CAZ/cl,AMC and TZP. Carbapenems did not show inoculum effect withany type of ESBLs.Conclusion According to the results of this study, carbapenemsremain the antibiotics of choice for the treatment of infectionscaused by ESBL-producing Enterobacteriaceae.