title: In vitro activities and targets of three cephem antibiotics against Haemophilus influenzae.
abstract: The antimicrobial activities of cefixime, cefpodoxime, and ceftibuten were determined with 18 ampicillin-susceptible (Amps), 13 ampicillin-resistant beta-lactamase-producing (AmprBLP), and 7 ampicillin-resistant non-beta-lactamase-producing (AmprNBLP) strains of Haemophilus influenzae. An effect of inoculum density on apparent MIC, the bactericidal activity of these agents, and the targets of the three cephems were determined. The MICs of cefixime, cefpodoxime, and ceftibuten for 90% of the Amps and AmprBLP isolates were 0.04, 0.08, and 0.08 microgram/ml, respectively. In contrast, the MICs for 90% of the AmprNBLP strains were 0.96, 1.92, and 7.68 micrograms/ml. No significant inoculum effect was observed for any group of strains comparing inocula of 10(3) and 10(5) CFU, whereas only the AmprNBLP isolates showed a marked effect at an inoculum of 10(6) CFU. Although bactericidal levels were achieved for the Amps and AmprBLP strains, tolerance to cefixime and ceftibuten was observed. The bactericidal activity for the AmprNBLP strains was limited, with cefixime showing the highest activity of the three cephems. Penicillin-binding proteins 2, 4, and 5 revealed high affinity, with 50% inhibitory concentration levels below the MIC for all three cephems, suggesting that these are important targets of these agents in H. influenzae. We conclude that the cephems are highly active in vitro against Amps and AmprBLP strains of H. influenzae, but less so against AmprNBLP isolates.
authors.affiliation: Division of Infectious Disease, Children's Hospital and Medical Center, Seattle, Washington.
authors.forename: P M
authors.initials: PM
authors.lastname: Mendelman
authors.forename: L L
authors.initials: LL
authors.lastname: Henritzy
authors.forename: D O
authors.initials: DO
authors.lastname: Chaffin
authors.forename: K
authors.initials: K
authors.lastname: Lent
authors.forename: A L
authors.initials: AL
authors.lastname: Smith
authors.forename: T L
authors.initials: TL
authors.lastname: Stull
authors.forename: E A
authors.initials: EA
authors.lastname: Wiley
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D020682:Cefixime; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D003470:Culture Media; D006193:Haemophilus influenzae / Q000187:drug effects*; D006602:Hexosyltransferases; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D010641:Phenotype
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D003470:Culture Media; D046915:Penicillin-Binding Proteins; D000667:Ampicillin; D020682:Cefixime; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D002439:Cefotaxime