title: Comparison of the inoculum effect of cefoxitin and other cephalosporins and of beta-lactamase inhibitors and their penicillin-derived components on the Bacteroides fragilis group.
abstract: We compared the inoculum effects for 109 recent clinical isolates of the Bacteroides fragilis group of cefoxitin, cefotetan, ceftizoxime, ceftriaxone, and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) and their penicillin-derived components. Bactericidal activity was assayed and morphologic changes were monitored for selected strains exhibiting a large inoculum effect. Ceftizoxime demonstrated the largest inoculum effect, followed by cefotetan and ceftriaxone. The large inoculum effect of ceftizoxime and ceftriaxone was correlated with filamentous transformation at the high inoculum (10(8) CFU/ml) and lack of bactericidal activity suggesting drug destruction or inactivation. Cefotetan was bactericidal for B. fragilis isolates but not for other members of the B. fragilis group. Cefoxitin showed the least inoculum effect and was consistently bactericidal at high (10(8) CFU/ml), standard (10(6) CFU/ml), and low (10(4) CFU/ml) inocula, followed by ampicillin-sulbactam. Piperacillin-tazobactam and ticarcillin-clavulanic acid showed an intermediate inoculum effect. The degree of inoculum effect observed generally correlated with bactericidal activity at all inocula.
authors.affiliation: R. M. Alden Research Laboratory, Santa Monica Hospital Medical Center, California 90404.
authors.forename: E J
authors.initials: EJ
authors.lastname: Goldstein
authors.forename: D M
authors.initials: DM
authors.lastname: Citron
authors.forename: C E
authors.initials: CE
authors.lastname: Cherubin
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001441:Bacteroides fragilis / Q000187:drug effects*; D002440:Cefoxitin / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; D002440:Cefoxitin