Laboratory and clinical studies on cefozopran

The newly developed injectable cephem, cefozopran (CZOP), was evaluated in vitro and in vivo. The results were as follows; 1. Antimicrobial activity : Minimal inhibitory concentrations (MICs) against 510 clinical isolates including 16 different species were determined by the microbroth dilution method and were compared with those of imipenem, ceftizoxime, ceftazidime, and cefuzonam. CZOP showed excellent antimicrobial activity at the same level as cefuzonam against gram-positive bacteria including MRSA, although the MICs were superior to that of imipenem. The MIC values of CZOP for gram-negative bacteria except P. vulgaris were equivalent to those of other cephems tested. Especially for C. freundii and E. cloacae, which produce cephalospolinase, CZOP have stronger antibacterial activity in comparison with other cephems. 2. CZOP concentrations in serum and sputum : To 7 patients with chronic respiratory tract infection, CZOP was given intravenously and concentrations were measured in serum and sputum. The peak serum concentrations, from 19.8 μg/ml to 118.6μg/ml, were observed immediately after infusion, and the peak sputum concentrations, from 1.0 μg/ml to 5.6 μg/ml, 2∼6 hours after infusion. The penetration ratio into sputum was 1.4∼10.6 %, suggesting that CZOP had rapid and good penetration into the lung. 3. Clinical efficacy and adverse reactions : Forty-eight patients with pulmonary infections were treated with CZOP, and the overall efficacy rate was 84.4 % (excellent in 12, good in 26, fair in 1, poor in 6 and not evaluable in 3). Among side effects, diarrhea was observed in 1 case, nausea in 1, itching, fever and lymphnode swelling in 1, eruption in 2 and itching and eruption in 1. Among abnormal laboratory findings, the elevation of GOT and GPT was observed in 2 cases, the elevation of GPT in 2, the elevation of LDH in 1, leukopenia in 4, neutropenia in 1 and an increase in the number of eosinophils in 4. These abnormalities were all mild and transient, suggesting that CZOP is a useful and safe antibacterial agent.