In vitro and in vivo antibacterial activity of E1010, a new injectable carbapenem

Background: Preliminary studies indicate that the new antipseudomonal carba penem E1010 is effective against a broad spectrum of bacteria. Objective: The aim of this study was to examine the in vitro and in vivo ac tivity of E1010 against anaerobes that commonly occur in patients with obst etric and gynecologic bacterial infections. Methods: In the in vitro phase of the study, 234 clinical isolates of 9 aer obic and anaerobic pathogens were collected from patients with obstetric an d gynecologic infections. Minimum inhibitory concentrations (MICs) of E1010 were determined by an agar dilution method and compared with those of pani penem, imipenem, meropenem, and ceftazidime. In the in vivo phase, mice wer e inoculated with a suspension of Bacteroides fragilis isolated from a pati ent with pelvic peritonitis and were then treated with E1010 20 mg/kg or im ipenem/cilastatin 20 mg/kg TID for 5 days. Therapeutic efficacy was assesse d based on the incidence of intra-abdominal abscesses and viable bacterial cell counts 5 days after bacterial inoculation. Results: In vitro, E1010 inhibited >90% of clinical isolates of Streptococc us agalactiae, Escherichia coli, Enterococcus faecalis, Enterobacter cloaca e, Citrobacter freundii, Pseudomonas aeruginosa, Peptostreptococcus magnus, B fragilis, and Prevotella bivia. The MIC of E1010 against P aeruginosa wa s greater than those of panipenem, imipenem, and meropenem. In vivo, E1010 inhibited abscess formation and significantly decreased viable cell counts in abscesses compared with the untreated group (P<0.05). In vivo therapeuti c efficacy, as measured by decreases in the viable cell count, was equivale nt to that of imipenem/cilastatin. Conclusion: These results suggest that E1010 may be useful in the treatment of anaerobic obstetric/gynecologic infections.