Activity of cefoperazone against ampicillin-resistant bacteria in agar and broth dilution tests

Examination of the activity of cefoperazone against ampicillin-resistant, gramnegative bacteria in agar dilution and simultaneously in broth dilution revealed that strains could be divided into three classes: class I strains were susceptible in agar (mean minimal inhibitory concentration [MIC], 0.5 mg/liter) as well as in broth dilution (mean MIC, 1.5 mg/liter), class II strains were susceptible in agar (MIC, 0.9 mg/liter), but resistant in broth dilution (MIC, 182 mg/liter); and class III strains were highly resistant in both test systems. Among 100 randomly selected ampicillin-resistant Escherichia coli cultures, 51 belonged to class I and 49 belonged to class II. Class III E. coli strains were much rarer. Similar results were obtained with cefamandole and cephalothin, but not with six other second-and third-generation cephalosporins. MICs of cefoperazone against cultures of all three classes were influenced by initial inoculum size. The inoculum effect was greatest with class II strains. Examination of bactericidal activity by cefoperazone showed killing of class I and class II E. coli strains and of class III strains of other genera during the first hours of incubation and regrowth after the drug was destroyed by the action of TEM beta-lactamase (penicillinase). Representative class I bacteria produced 10 to 100 times less TEM beta-lactamase than did class II strains. It appeared that the quantitative difference in TEM production was the reason for the different resistance phenotypes in class I and class II strains. Salmonella and Klebsiella strains of class III produced the same amounts of TEM beta-lactamase as did class II E. coli strains. Probably, some factors other than beta-lactamase contributed to the class III phenotype in these species.