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.
Chandrasekar
P H
PH
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
Sluchak
J A
JA
Kruse
J A
JA
D000380:Agranulocytosis / Q000139:chemically induced / Q000150:complications*; D000818:Animals; D002438:Cefoperazone / Q000097:blood / Q000627:therapeutic use; D015169:Colony Count, Microbial; D003520:Cyclophosphamide; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000097:blood / Q000627:therapeutic use*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D013407:Sulbactam / Q000097:blood / Q000627:therapeutic use; D001618:beta-Lactamases / Q000096:biosynthesis
D002438:Cefoperazone; D003520:Cyclophosphamide; D001618:beta-Lactamases; D013407:Sulbactam