Laboratory and clinical evaluation of SY5555, a new oral penem antibiotic

• Published in: CHEMOTHERAPY Vol. 42; no. Supplement1; pp. 389 - 399
• Main Authors: Iwagaki, Akitaka, Oishi, Kazunori, Watanabe, Kiwao, Nagatake, Tsuyoshi, Matsumoto, Keizo, Takasugi, Masakazu, Ishikawa, Hidefumi, Yamamoto, Masashi, Shishido, Harumi, Nagai, Hideaki, Uzuka, Yoshio
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Chemotherapy 1994
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.42.Supplement1_389

We performed laboratory and clinical studies on SY5555, a new oral penem, in order to evaluate its usefulness in respiratory tract infections. The antibacterial activity of SY5555 against respiratory pathogenic bacteria was superior to those of reference β-lactam oral antibiotics used in the study; its MIC50 and MIC90 were 0.006 and 0.025μg/ml against Streptococcus pneumoniae (45 strains), 0.2 and 0.78μg/ml against Haemophilus influenzae (36 strains), 0.39 and 0.78μg/ml against Branhamella catarrhalis (36 strains), respectively. SY5555 showed good activity against methicillin-susceptible Staphylococcus aureus with an MIC range of 0.05-0.78μg/ml, its MIC50 and MIC90 were 0.05 and 0.1μg/ml but the drug showed inferior activity against methicillin-resistant S. aureus except 1 strain. The maximal plasma level of SY5555 was 2.13μg/ml after a single 200mg dose, and 1.52 or 4.52μg/ml after a single 300mg dose. The maximal sputum levels of SY5555 were 0.02 (0.9%), 0.04 (2.6%) and 0.47μg/ml (10.4%) after single doses of 200 mg, 300 mg and 300 mg respectively (ratio of maximal sputum level to peak serum level). Twenty-nine patients with respiratory infections were studied for the clinical evaluation of SY5555, which was administered at doses of 200mg, 300mg or 400mg t. i. d. for 3 to 14 days. The clinical efficacy was excellent in 4, good in 17, fair in 5 and poor in 3. The overall efficacy rate was 72.4%(21/29). Causative bacteria were H. influenzae (7), B. catarrhalis (5), S. pneumoniae (5), Klebsiella pneumoniae (2) and Haemophilus parainfluenzae (2), 13 out of 21 strains (61.9%) being eradicated. Diarrhea was observed as a side effect in 1 case. Laboratory findings showed a slight elevation of eosinophils in 1 patient. We concluded that a daily dose of 300mg (t. i. d.) was a suitable dose of SY5555 in the treatment of respiratory infections.