New parenteral cephem, cefozopran, in treatment of patients with surgical infections

• Published in: CHEMOTHERAPY Vol. 41; no. Supplement4; pp. 349 - 372
• Main Authors: Morimoto, Ken, Kinoshita, Hiroaki, Nakatani, Shuichi, Kubo, Shoji, Kubota, Daisuke, Ueda, Takami, Fujimoto, Mikio, Ohno, Kohichi, Ohmori, Kunio, Doi, Susumu, Hirata, Sanae, Yamazaki, Osamu, Sakai, Katsuji
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 25-12-1993
• Subjects: cefozopran; cephems; mastectomy wound seroma
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.41.Supplement4_349

We gave cefozopran, a new semisynthetic parenteral cephem, to five patients with wound seroma after radical mastectomy, in a study of its pharmacokinetics. We also treated 58 surgical infections with this drug and evaluted its clinical efficacy in 56 of them. In the pharmacokinetic study, 1.0 g was infused intravenously for 30 min. The peak levels in the serum were 64.6 to 125.7 μg/ml at 0.5 hour, with a decrease to <0.3 to 8.4 μg/ml at 6 hours. At 24 hours, the drug was not detected in the serum. The peak levels in the seroma were 14.4 to 28.0 μg/ml at 2 to 4 hours, with a decrease to 8.4 to 21.0 μg/ml at 6 hours. The levels in the serum were simulated well by a two-compartment model, and the levels in the seroma were simulated well by a one-compartment model. Areas under the curve (AUC) were higher in the seroma than in the serum for four patients. Of the 56 infections, clinical efficacy was excellent in 38 (68%), good in 9, fair in 8, and poor in one, with an efficacy rate of 84%. The efficacy was not correlated to the number of strains isolated per patient or the severity of the infection. The bacteriological response for each bacterium isolated was evaluated. Sixty-five strains (92%) were eradicated, two strains decreased, and four strains persisted, with an eradication rate of 92%. The bacteriological response of the host was evaluated in 40 infections. Bacteria were eradicated in 33 infections (83%), decreased in three, were replaced in two, and persisted in two, with an eradication rate of 88%. In 23 single-bacterial infections, bacteria were eradicated in 20 (87%). In 17 mixed-bacterial infections, bacteria were eradicated in 13 (76%) and replaced in two infections, with an eradication rate of 88%. Minimum inhibitory concentrations (MICs) were calculated for the 71 bacterial strains isolated. In the 65 strains evaluated for the bacteriological response, no correlation was observed between MIC and eradication. No side effects were observed during this trial. Large abnormal changes in laboratory data during treatment with this drug were analyzed by stratification into subgruops classified by the factors responsible. Hemoglobin decreased in three of the nine patients with primary peritonitis (p=0.012) and in four of the 24 patients with serious infections (p=0.031). Abnormal changes in liver enzymes were observed in seven of the 24 patients (p=0.029). The number of abnormal changes observed did not depend on the total dose, although in seven of the 25 patients given a total dose of 20 to 29 g, abnormal changes in liver enzymes were observed (p=0.10). These abnormal changes seemed to arise from factors other than cefozopran. These results showed that a high efficacy rate could be expected with cefozopran without serious toxicity when used for surgical infections.