Listeria monocytogenes is an important cause of bacteremia and meningitis in neonates and immunocompromised patients (7,10,12,17,20,22). Although penicillin G and ampicillin (with or without an aminoglycoside) are considered the drugs of choice for the treatment of Listeria infection, there is a need for alternative drugs in cases of penicillin-allergic patients and in therapeutic failures (2, 30).'Imipenem (N-formimidoyl thienamycin), unlike newer cephalosporins, appears to be a promising candidate because of its excellent in vitro activity against L. monocytogenes with an MIC for 90% of strains tested of s 0.12 ,ug/ml (9,13,21,31). In addition, combinations of imipenem-gentamicin have been shown to be synergistic in vitro against L. monocytogenes (9). However, in vivo evaluation of imipenem against L. monocytogenes has not been reported. The present study therefore was performed to examine the in vitro and in vivo activities of imipenem and imipenemgentamicin in comparison with ampicillin and ampicillingentamicin against L. monocytogenes.
MATERIALS AND METHODSOrganism. A clinical strain of L. monocytogenes (strain LM2) that was isolated from the blood of an infant with sepsis was used in the in vitro and in vivo experiments.In vitro studies. MICs and MBCs were measured in Todd-Hewitt broth (Difco Laboratories, Detroit, Mich.) by the standard macrobroth dilution method (29). The antimicrobial agents tested were imipenem (Merck Sharp & Dohme Research Laboratories, Rahway, N.J.), ampicillin trihydrate (Bristol Laboratories, Syracuse, N.Y.), and gentamicin sulfate (Schering Corp., Kenilworth, N.J.). Antimicrobial agents were diluted serially twofold from 16 to 0.03 ,ug/ml in Todd-Hewitt broth. An inoculum of approximately 5 x 105 CFUJ of L. monocytogenes per ml was prepared from late logarithmic phase cultures. Equal volumes (0.5 ml) of antibiotic and bacterial dilutions were mixed and incubated at 37°C for 24 h. The MIC was defined as the lowest antibiotic concentration exhibiting no visual turbidity. From each tube, 0.01 ml was transferred to a quadrant of sheep blood agar ahd incubated at 37°C for 24 h to determine the MBC, which was defined as the lowest concentration of antibiotics resulting in -99.9% killing of the original ipoculum.The MICs and MBCs of imipenem-gentamicin and ampicillin-gentamicin were measured in Todd-Hewitt broth (1). Twofold dilutions of each antibiotic were used in a checkerboard fashion. MIC and MBC endpoints were read as described above for each antibiotic alone and in various combinations. The results were expressed as the fractional bactericidal concentration index, which was calculated by the following formula (3, 23): (MBC of drug A in combination with drug B/MBC of drug A) + (MBC of drug B in combination with drug A/MBC of drug B) (for studies of imipenem-gentamicin, drug A was imipenem and drug B was gentamicin, or vice versa; for studies of ampicillingentamicin, drug A was ampicillin and drug B was gentamicin, or vice versa). When the FBC index was less than 0.5, the combinatio...
