Implications of beta-lactamase-inhibitor combinations.
Resistance of many species of bacteria to beta-lactam antibiotics is mediated via inactivation by beta-lactamase. Beta-lactamase inhibitors irreversibly bind to beta-lactamases and thus can prevent the destruction of active beta-lactam antibiotics. In the United States three beta-lactam-antibiotic/beta-lactam-inhibitor combinations are commercially available--the orally absorbed amoxicillin/clavulanic acid (A/C), the parenteral formulations of ampicillin/sulbactam (A/S) and ticarcillin/clavulanate (T/C). In a multicenter study that focused on T/C, the in vitro activity of amoxicillin (AMOX), ampicillin (AMP) and ticarcillin (TIC) against Neisseria gonorrhoeae and Haemophilus influenzae was obliterated when beta-lactamase-positive strains were tested, but all tested strains were susceptible to the antibiotics in combination with their respective beta-lactamase inhibitors. Clavulanic acid improved the activity of TIC against most species of Enterobacteriaceae but not against those Enterobacteriaceae that elaborate type I beta-lactamase or against non-Enterobacteriaceae gram-negative bacilli (except for Pseudomonas maltophilia). Staphylococci are generally beta-lactamase positive and considered resistant to AMP and TIC, but greater than 99% of 1,137 Staphylococcus aureus isolates and 92% of coagulase-negative staphylococcal isolates were susceptible to T/C, with comparable figures obtained for A/C and A/S. The activity of TIC against Bacteroides fragilis was improved up to 64-fold by clavulanic acid, with a definite but less pronounced effect on the non-fragilis Bacteroides species. Ninety-seven percent of strains of other anaerobic genera were susceptible to both TIC and T/C.(ABSTRACT TRUNCATED AT 250 WORDS)
Fuchs
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St. Vincent Hospital, Portland, Oregon.
Barry
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D000658:Amoxicillin / Q000494:pharmacology; D000667:Ampicillin / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013407:Sulbactam / Q000494:pharmacology; D013982:Ticarcillin / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors
D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D000667:Ampicillin; D000658:Amoxicillin; D013982:Ticarcillin; D013407:Sulbactam