Therapy with cefoperazone plus sulbactam against disseminated infection due to cefoperazone-resistant Pseudomonas aeruginosa and Escherichia coli in granulocytopenic mice.

Using a granulocytopenic murine model, we evaluated the efficacy of cefoperazone plus sulbactam against disseminated infection due to isolates of beta-lactamase-producing, cefoperazone-resistant (MIC, > or = 50 micrograms/ml) Escherichia coli and Pseudomonas aeruginosa. Both isolates were susceptible in vitro to cefoperazone plus sulbactam (MIC, < or = 6.3 micrograms/ml). Mice rendered granulocytopenic with cyclophosphamide were divided into three groups: group A--infected, untreated mice (controls); group B--infected, cefoperazone-treated mice (700 mg/kg of body weight); and group C--infected, cefoperazone-plus-sulbactam-treated mice (700 mg plus 350 mg). In the E. coli experiment, survival rates in groups A, B, and C were 25, 46, and 73%, respectively. In the experiment with P. aeruginosa, survival rates in groups A, B, and C were 0, 10, and 50%, respectively (P < 0.001). Highly significant differences also were noted for colony counts in the blood, liver, and spleen of group C mice versus group A or B mice in both experiments. Thus, cefoperazone plus sulbactam appears to be a promising combination for the treatment of infections due to certain cefoperazone-resistant gram-negative bacilli, including P. aeruginosa.