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

Abstract

Background: Preliminary studies indicate that the new antipseudomonal carbapenem E1010 is effective against a broad spectrum of bacteria. Objective: The aim of this study was to examine the in vitro and in vivo activity of E1010 against anaerobes that commonly occur in patients with obstetric and gynecologic bacterial infections. Methods: In the in vitro phase of the study, 234 clinical isolates of 9 aerobic and anaerobic pathogens were collected from patients with obstetric and gynecologic infections. Minimum inhibitory concentrations (MICs) of E1010 were determined by an agar dilution method and compared with those of panipenem, imipenem, meropenem, and ceftazidime. In the in vivo phase, mice were inoculated with a suspension of Bacteroides fragilis isolated from a patient with pelvic peritonitis and were then treated with E1010 20 mg/kg or imipenem/cilastatin 20 mg/kg TID for 5 days. Therapeutic efficacy was assessed 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 Streptococcus agalactiae, Escherichia coli, Enterococcus faecalis, Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, Peptostreptococcus magnus, B fragilis, and Prevotella bivia. The MIC of E1010 against P aeruginosa was 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 therapeutic efficacy, as measured by decreases in the viable cell count, was equivalent to that of imipenem/cilastatin. Conclusion: These results suggest that E1010 may be useful in the treatment of anaerobic obstetric/gynecologic infections.