engleski

Effect of inoculum size on the antibacterial activity of cefprime and cefepime against Klebsiella pneumoniae strains producing SHV extended-spectrum beta-lactamases

Objective: to determine the effects of varying inoculum size on in-vitro susceptibility of SHV extended-spectrum b-lactamase (ESBL)- producing Klebsiella pneumoniae isolates to cefepime and cefpirome compared to previously established cephalosporins and aztreonam. Methodology: Antibiotic susceptibilities were determined by disk-diffusion test, MIC broth microdilution method and in time-kill studies. The strains were classified in five groups acccording to the type of b-lactamase they produce: SHV-2, SHV-5, SHV-12, putative SHV ESBL producers and ESBL negative Klebsiellae. Results: Antibacterial activity of cefpirome and cefepime was comparable to that of cefotaxime but it was significantly stronger than of ceftazidime and aztreonam. An inoculum effect was detected for all broad-spectrum cephalosporins but it was more pronounced with cefpirome and cefepime compared to older cephalosporins. A marked increase in MIC50 and MIC90 was seen against K. pneumoniae strains producing all three types of SHV ESBLs at inoculum size of 107 CFU/ml compared to 103 CFU/ml. The disk-diffusion test turned out not to be enough sensitive method for detection of an inoculum effect, particularly for cefepime. Conclusions:The present study found that most SHV producing Klebsiellae produce MICs of cefpirome that imply susceptibility at the low and moderate inoculum sizes and to cefepime at low inoculum size in spite of the fact that according to NCCLS all ESBL producers should be considered resistant to all cephalosporins, with independence of MIC values. With a high inoculum most of the of the strains seemed to be resistant to both antibiotics. Furthermore bactericidal activity of cefpirome and cefepime against isogenenic E. coli strains producing SHV-2, SHV-4 and SHV-5 b-lactamases respectively, was also inoculum- dependent. Bactericidal activity against SHV-4 and SHV-5 b-lactamase producers was obtained only at low and moderate inocula while SHV-2 b-lactamase producer was efficiantly killed with both antibiotics regardless of the inoculum size.

extended-spectrum beta-lactamases; cefpirome; cefepime

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