Laboratory and clinical studies of SY5555

A newly developed oral penem, SY5555, was compared in vitro and in vivo with imipenem (IPM), cefixime (CFIX) and cefteram (CFTM). The results were as follows: 1. Antimicrobial activity: The minimum inhibitory concentrations (MICs) against 515 clinical isolates of 16 different species were determined by the microbroth dilution method. SY5555 showed excellent antimicrobial activity against gram-positive and -negative bacteria except for methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter anitratus. The MICs of SY5555 were nearly equal to those of IPM, and those for gram-positive bacteria were greater than those of CFIX and CFTM. 2. SY5555 concentrations in serum and sputum: A patient was given 300 mg of SY5555 orally before meal and its concentrations in serum and sputum were measured at intervals using HPLC. A peak serum concentration of 1.32 μg/ml was achieved 1 hour after administration, and the peak sputum level of 0.45 μg/ml was observed 1~2 hours after administration. This suggests that SY5555 has rapid and good penetration into the lung. Similarly, two patients were given 300 mg of SY5555 orally after a meal. Peak concentrations in serum of 1.17 μg/ml and 1.54 μg/ml were achieved 2 hours after the administration. 3. Clinical efficacy and adverse reactions: 14 patients with respiratory tract infections were treated with SY5555, and the overall efficacy rate was 66.7%(good in 8 cases, fair in 2, poor in 2, not evaluable in 2). As to side effects, nausea and loose stool were observed in 2 cases but improved after the completion of SY5555 treatment. As to abnormal laboratory findings, eosinophillia in 1 case, decrease of platelets in 1 and elevation of BUN in 1 were observed, but they were mild and transient.