title: Sodium clavulanate potentiation of cephalosporin activity against clinical isolates of cephalothin-resistant Klebsiella pneumoniae.
abstract: Plasmid-carrying Klebsiella pneunomiae clinical isolates with agar dilution minimum inhibitory concentrations (MIC) of 32 mug/ml or greater were tested for in vitro potentiation of cephalothin activity by clavulanic acid (BRL-14151), an inhibitor of beta-lactamases. The addition of 10 mug of clavulanate per ml caused greater than a 500-fold reduction in geometric mean cephalothin agar dilution MIC, with lesser but significant reductions resulting from clavulanate concentrations of 5 or 1 mug/ml. Clavulanate-potentiated reduction of cephalothin MICs in broth against resistant Klebsiella were comparable to reduction in agar dilution MICs as a rule. However, a low concentration (1 mug/ml) of clavulanate produced cephalothin MICs in broth several-fold higher than by the agar dilution method. Modest cephalothin-potentiating effects of clavulanate on cephalothin-susceptible strains and on cefoxitin against cephalothin-resistant Klebsiella strongly suggested that the major effect of clavulanate was beta-lactamase inhibition.
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002510:Cephalosporinase / Q000096:biosynthesis; D002511:Cephalosporins / Q000494:pharmacology*; D002512:Cephalothin / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D013997:Time Factors; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D000581:Amidohydrolases; D002510:Cephalosporinase; D002512:Cephalothin