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Activity of cefepime against ceftazidime-resistant gram-negative bacilli using low and high inocula
Journal article   Peer reviewed

Activity of cefepime against ceftazidime-resistant gram-negative bacilli using low and high inocula

C C Johnson, L Livornese, M J Gold, P G Pitsakis, S Taylor and M E Levison
Journal of antimicrobial chemotherapy, v 35(6), pp 765-773
Jun 1995
PMID: 7559188

Abstract

Gram-Negative Bacteria - enzymology Microbial Sensitivity Tests Gram-Negative Bacteria - drug effects Enterobacter cloacae - drug effects Cefepime Ceftazidime - pharmacology Cephalosporin Resistance Enterobacter - drug effects Kinetics Pseudomonas aeruginosa - drug effects beta-Lactamases - metabolism Cephalosporins - pharmacology
Cefepime is a broad-spectrum cephalosporin that is reported to have enhanced activity against ceftazidime-resistant Gram-negative bacilli. In this study the effects of varying inoculum size on in-vitro susceptibility to cefepime and other selected antimicrobial agents were determined by agar dilution MICs and in time-kill studies. Among strains of Pseudomonas aeruginosa (n = 55) and Enterobacter spp (n = 56) that had previously been identified as ceftazidime-resistant, 73% and 96% were susceptible to cefepime (MIC < or = 16 mg/L), respectively, when tested with an inoculum of 10(4) cfu. However, with an inoculum of 10(7) cfu, 98% and 100% of strains were resistant, respectively. Furthermore, the bactericidal activity of cefepime against ceftazidime-resistant isolates was also inoculum-dependent. In time-kill studies, bactericidal action was obtained only at the lowest concentration of organisms (10(4) cfu/mL). beta-Lactamase extracted from an isolate of P. aeruginosa that demonstrated an inoculum effect had a lower affinity for cefepime than for ceftazidime. Overall, cefepime proved to be more resistant to hydrolysis by the beta-lactamase. However, differences in kinetics of the beta-lactamase against cefepime or ceftazidime do not appear to be of consequence in determining susceptibility of P. aeruginosa and Enterobacter spp. at high bacterial densities, since most strains with chromosomally-mediated beta-lactamase are highly resistant.

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Web of Science research areas
Infectious Diseases
Microbiology
Pharmacology & Pharmacy
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