In vitro antimicrobial activity of ritipenem acoxil and its therapeutic efficacy in respiratory tract infections

We measured the in vitro antimicrobial activity of ritipenem acoxil (RIPM-AC), a new oral penem antibiotic developed in Italy, and evaluated its therapeutic efficacy in respiratory tract infections. The minimum inhibitory concentrations (MICs) of RIPM-AC, cefteram (CFTM) and cefaclor (CCL) against 20 strains each of methicillin‒susceptible 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, RIPM-AC was the most active against MSSA and MRSA of the above three antibiotics. Against H.influenzae, E.coli, K.pneumoniae, E.cloacae and S.marcescens, RIPM-AC was more active than CCL, but less active than CFTM. RIPM-AC was considered to be less potent against infections caused by P.aeruginosa. An oral dose of 450-1200mg of RIPM-AC was given daily to 37 patients for 2 to 18 days (mean: 11.7 days) : 5 patients with acute bronchitis, 4 patients with chronic bronchitis, 14 patients with bronchiectasis plus infection, one patient each with pulmonary emphysema plus infection and pulmonary fibrosis plus infection, 11 patients with acute pneumonia and one patient with pulmonary tuberculosis. Cl inical efficacy was excellent in 5, good in 22, fair in 6 and poor in 2 patients (efficacy rate : 77.1%). Two cases were excluded from clinical evaluation because one had pulmonary tuberculosis and because treatment in the other case was stopped on the second day due to adverse reaction. Clinical efficacy was poor in cases treated with low doses (450 mg), but was good in cases treated with 600, 900 or 1200mg of RIPM-AC. Eighteen strains were identified as causative organisms : 2 strains of S.aureus (one of them was MRSA), 3 strains each of Streptococcus pneumoniae and Moraxella catarrhalis, 8 strains of H.influenzae, and one strain each of P.aeruginosa and Pseudomonas putrefaciens. Eight of them were eradicated by administration of RIPM-AC. Anorexia occurred in one patient. Elevations of s-GOT, s-GPT and eosinophils as well as drug exanthema were observed in one patient. Elevation of s-GOT occurred in one patient. These adverse reactions disappeared after the completion of therapy. From the above results, we conclude that a daily dose of more than 600mg of RIPM-AC is required for the treatment of respiratory tract infections.