Comparative in vitro activity of cefoperazone and various combinations of cefoperazone/sulbactam

Cefoperazone with 2 and 4 micrograms/ml of sulbactam and in a 2:1 ratio was tested against 1258 clinical isolates of Gram-positive and Gram-negative bacteria, as well as against Gram-negative bacilli that had stably derepressed Type I beta-lactamase or that were hyperproductive of non-Type I beta-lactamases. The 2:1 cefoperazone/sulbactam combination was the most potent combination tested. With this combination cefoperazone minimum inhibitory concentrations (MICs) of 27 of 40 (67%) of the clinical isolates of Pseudomonas species and 64 of 67 (95%) of clinical isolates of the Enterobacteriaceae were reduced from greater than or equal to 64 micrograms/ml by at least two-fold. In contrast, cefoperazone MICs of greater than or equal to 64 micrograms/ml remained unchanged for 26 (65%) and 24 (60%) of Pseudomonas species and 35 (52%) and 30 (45%) of the Enterobacteriaceae in the presence of 2 and 4 micrograms/ml of sulbactam, respectively. Cefoperazone/sulbactam in the 2:1 ratio was also the most active combination against the mutants derepressed for Type I beta-lactamase. Although the 2:1 combination of cefoperazone/sulbactam had the greatest potency in vitro, it remains to be seen whether this combination is predictive of clinical outcome from treatment of cefoperazone-resistant Gram-negative bacilli with cefoperazone/sulbactam.