title: In vitro activity of clarithromycin and its 14-hydroxy-metabolite against 203 strains of Haemophilus influenzae.
abstract: The in vitro activity of clarithromycin alone and in combination with its primary human metabolite, 14-hydroxy-clarithromycin, was determined against 203 strains of Haemophilus influenzae. Microdilution broth MICs and MBCs of both clarithromycin and 14-hydroxy-clarithromycin were determined. The clarithromycin MIC50 was 4 mg/l and the MIC90 was 8 mg/l. The hydroxy metabolite was 2-4-fold more active with an MIC50 and MIC90 of 2 mg/l. The MBCs were equal to the MICs. The microbicidal effect of combinations of clarithromycin and 14-hydroxy-clarithromycin was tested using a microdilution checkerboard technique and the fractional inhibitory index was calculated. The combination was additive in 92% and synergistic in 8% of all strains of H. influenzae tested; no antagonism was found. The results were independent of the site of isolation of the strain or presence of beta-lactamase. These findings suggest the potential clinical utility of clarithromycin for the treatment of H. influenzae infections.
authors.affiliation: Dept. of Microbiology, Faculté de Médecine, Université Laval, Quebec, Canada.
authors.forename: M G
authors.initials: MG
authors.lastname: Bergeron
authors.forename: M
authors.initials: M
authors.lastname: Bernier
authors.forename: J
authors.initials: J
authors.lastname: L'Ecuyer
mesh_terms: D015373:Bacterial Typing Techniques; D002170:Canada / Q000453:epidemiology; D017291:Clarithromycin / Q000031:analogs & derivatives; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004917:Erythromycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006192:Haemophilus Infections / Q000453:epidemiology / Q000382:microbiology; D006193:Haemophilus influenzae / Q000145:classification / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: C056228:14-hydroxyclarithromycin; D004917:Erythromycin; D001618:beta-Lactamases; D017291:Clarithromycin