title: Clarithromycin in vitro activity enhanced by its major metabolite, 14-hydroxyclarithromycin.
abstract: 14-Hydroxyclarithromycin, an active metabolite of clarithromycin, was compared for antimicrobial activity alone and in combination with the parent compound. The 14-hydroxyclarithromycin potency was comparable to that of clarithromycin, but was more active against Haemophilus influenzae (MIC50, 1 microgram/ml). Combination MICs at pharmacokinetic ratios produced end points equal to the most active component of the combination. However, checkerboard MICs and kill-curve studies suggested enhanced interactive effects. Partial synergy and additive interactions were demonstrated in 96% of strains tested with synergy (partial) most often observed among the Enterococcus faecalis, H. influenzae, and staphylococci. To determine the best in vitro test methods for predicting the value of 14-hydroxyclarithromycin, combination disks or ratio MIC tests may not be practical. A modification of the proposed clarithromycin-susceptible breakpoint (less than or equal to 2 micrograms/ml) upward to less than or equal to 4 micrograms/ml (greater than or equal to 14 mm) was suggested to recognize the additional activity contributed by the 14-hydroxy metabolite. This modification should be applied, limited to susceptibility tests of H. influenzae and possibly the enterococci.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City.
authors.forename: W W
authors.initials: WW
authors.lastname: Hoover
authors.forename: M S
authors.initials: MS
authors.lastname: Barrett
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D001419:Bacteria / Q000187:drug effects*; D017291:Clarithromycin / Q000031:analogs & derivatives; D004347:Drug Interactions; D013293:Enterococcus faecalis / Q000187:drug effects; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects; D015610:Serum Bactericidal Test; D013210:Staphylococcus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects
chemical_list: C056228:14-hydroxyclarithromycin; D004917:Erythromycin; D017291:Clarithromycin