In vitro antimicrobial activity and therapeutic efficacy of SY5555 in respiratory tract infections

We measured the in vitro antimicrobial activity of SY5555, a new oral penem antibiotic developed in Japan, and evaluated its therapeutic efficacy in respiratory tract infections. The minimum inhibitory concentrations (MICs) of SY5555, cefteram (CFTM) and cefaclor (CCL) against 20 strains each of methicillin-suscptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa, and 18 strains of Haemophilus influenzae, were determined by the micro-broth dilution method using the Dynatech MIC 2000 system. As shown by the MICs, SY5555 was the most active against MSSA among three antibiotics. Against H. influenzae and E. coli, SY5555 was more active than CCL, but less active than CFTM. SY5555 was as active as CCL against K. pneumoniae, and as active as CFTM against E. cloacae and S. marcescens. SY5555 was slightly more active than CFTM and CCL against MRSA and P. aeruginosa, but was considered to be less potent against clinical infections caused by these bacteria. An oral dose of 300~900mg of SY5555 was given daily to 11 patients for 3 to 27 days (mean: 12.2 days): 2 each with chronic bronchitis and bronchiectasis plus infection, one each with old pulmonary tuberculosis plus infection and pulmonary emphysema plus infection and 5 with acute pneumonia. Clinical efficacy was excellent in 3 patients, good in 2, fair in 2 and poor in 4 (efficacy rate: 45.5%). Clinical efficacy was poor in cases treated with low doses (300 mg and 450 mg), and was good in cases treated with 900 mg of SY5555. Seven strains were identified as causative organisms: 2 strains each of S. aureus and P. aeruginosa, one strain each of Streptococcus pneumoniae, H. influenzae and K. pneumoniae. Three of them were eradicated by administration of SY5555. No clinical adverse reactions or abnormalities in laboratory data were observed during or after the therapy. From the above results, we conclude that a daily dose of SY5555 above 600 mg is required for the treatment of respiratory tract infections.