In vitro antimicrobial activity, penetration into sputum and therapeutic efficacy of S-1108 in respiratory tract infections

Akira Watanabe, Yoshihiro Honda, Yutaka Tokue, Naoto Kitamura, Satoru Shoji, Iiiroaki Kikuchi, Kiyoshi Konno, Tsuneo Sayama, Mitsunobu Honma, Masakichi Motomiya, Satoshi Shindo

    Research output: Contribution to journalArticlepeer-review

    Abstract

    We measured the in vitro antimicrobial activity, and serum and sputum concentrations of S-1108, a new oral cephem developed in Japan, and evaluated its therapeutic efficacy in respiratory tract infections. The minimum inhibitory concentrations (MICs) of S-1006, cefixime (CFIX), cefteram pivoxil (CFTM-PI) and cefaclor (CCL) against 20strains each of methicillin-susceptible Staphylococcs aureus (MSSA), methicillin-resistant Stphylococcus aureus (MRSA), Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa were determine by the micro-broth dilution method using the Dynatech MIC 2000 system. As shown by the MICs, S-1006 was more active than the others against MSSA, H. influenzae and P. aeruginosa. Against Enterobacteriaceae, S-1006 was as active as cefteram and cefixime. No agents tested displayed potent activity against either MRSA or P. aeruginosa. The concentration of S-1006 in the serum of the three patients with bronchiectasis was highest 2 to 3 hours after oral administration of 200 mg (2.17, 1.08 and 0.66μ/ml). Thereafter, the maximum concentrations of S-1006 achieved in sputum were 0.04, 0.06, and 0.03μgl/ml, respectively. Thus, the maximum penetration rates were 1.84, 5.56 and 4.55%, respectively (mean : 3.98%). An oral dose of 300~600 mg of S-1108 was given daily to 25 patients for 5 to 15 days (mean : 9.3 days) : 4 with acute bronchitis, 5 with chronic respiratory infections, 14 with acute pneumonia and one each with pulmonary tuberculosis and secondary infection in lung cancer. Three patients were excluded from clinical evaluation because one patient was diagnosed as having active pulmonary tuberculosis and two were seen in the outpatient clinic only once. Clinical efficacy was excellent in 2 patients and good in 20 (efficacy rate : 100%). Nineteen strains were identified as causative organisms : 1 strain of S. aureus, 6 strains of Streptococcus pneumoniae, 6 strains of Branhamella catarrhalis, 3 strains of H. influenzae, 1 strain of K. pneumoniae and 2 strains of P. aeruginosa. Fourteen out of 18 strains against which bacteriological effects could be evaluated were eradicated by administration of S-1108. Diarrhea was observed in three patients. Eosinophilia and elevation of transaminase values were observed in four patients each, but the adverse reactions disappeared after completion of therapy From the above results, we conclude that S-1108 is one of the most useful cephems for oral use as an agent of first choice in the treatment of respiratoty tract infections in outpatient clinics.

    Original languageEnglish
    Pages (from-to)217-230
    Number of pages14
    JournalChemotherapy
    Volume41
    DOIs
    Publication statusPublished - 1993 Jan 1

    ASJC Scopus subject areas

    • Pharmacology (medical)
    • Infectious Diseases
    • Pharmacology
    • Drug Discovery
    • Oncology

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