Influence of bacterial β-lactamase production on susceptibility in agar or broth to new cephalosporins

: Of 39 cephalothin-resistant (MIC > or =16 mg/l) strains of Enterobacteriaceae, 50% were inhibited by cefamandole 4 mg/l, cefoperazone 1 mg/l, cefuroxime 16 mg/l, cefoxitin 8 mg/l, ceftazidime 0.5 mg/l and moxalactam 0.1 mg/l in Mueller-Hinton agar with inocula of 106 bacteria/ml. The MICs in broth with the respective antibiotics were eight-, four-, two-, sixteen- and eightfold higher. Of 22 Pseudomonas aeruginosa strains, 50% were inhibited in agar by ceftazidime 1 mg/l and moxalactam 16 mg/l and in broth by 4 and 64 mg/l, respectively. Cefamandole was the most susceptible and ceftazidime and moxalactam the most stable to inactivation by crude beta-lactamase preparations from the strains. A higher broth/agar MIC ratio correlated, with some exceptions, to the production of active enzymes. Growth curves in the presence of antibiotic with or without beta-lactamase inhibitor confirmed that the elevated broth MICs were attributable to beta-lactamase production. High broth/agar MIC ratios were also found with strains that gave inactive preparations particularly against ceftazidime and moxalactam, which must be due to other factors.