title: Activity of cefepime against ceftazidime-resistant gram-negative bacilli using low and high inocula.
abstract: 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.
authors.affiliation: Medical College of Pennsylvania, Philadelphia, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Johnson
authors.forename: L
authors.initials: L
authors.lastname: Livornese
authors.forename: M J
authors.initials: MJ
authors.lastname: Gold
authors.forename: P G
authors.initials: PG
authors.lastname: Pitsakis
authors.forename: S
authors.initials: S
authors.lastname: Taylor
authors.forename: M E
authors.initials: ME
authors.lastname: Levison
mesh_terms: D000077723:Cefepime; D002442:Ceftazidime / Q000494:pharmacology*; D018550:Cephalosporin Resistance; D002511:Cephalosporins / Q000494:pharmacology*; D004754:Enterobacter / Q000187:drug effects; D016972:Enterobacter cloacae / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D000077723:Cefepime; D002442:Ceftazidime; D001618:beta-Lactamases