In vitro and in vivo activity of various antibiotics against Listeria monocytogenes type 4b.

Inadequate guidelines for the treatment of neonatal listeriosis led us to evaluate various antibiotics in a newborn rat model of Listeria monocytogenes type 4b sepsis. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC based on 99.9% killing), expressed as micrograms/ml, were determined for: ampicillin (MIC 0.46/MBC 3.20); ampicillin with subinhibitory concentrations of gentamicin (0.24/not done); erythromycin (0.14/3.59); gentamicin (0.38/1.11); gentamicin with subinhibitory concentrations of ampicillin (0.235/ND); piperacillin (2.7/16.8); rifampin (0.026/0.094); sulfamethoxazole (SMZ 47.5/ND); SMZ with subinhibitory concentrations of trimethoprim (0.74/1.48); trimethoprim (TMP 0.12/ND); and TMP with subinhibitory concentrations of SMZ (0.04/0.08). In the in vivo model, rats were challenged intraperitoneally with 2 X 10(6) cfu of L. monocytogenes at 3 days-of-age. Antibiotics (ampicillin, ampicillin + gentamicin, erythromycin, piperacillin or TMP/SMZ) were given every 12 h for 2 days starting on day 5 of life while rifampin was given once daily for 2 days. Survival tabulations and spleen cultures were done on day 8 of life. All animals who received antibiotics had better survival than the controls given saline (p less than 0.01 for rifampin, erythromycin, TMP/SMZ, ampicillin, ampicillin + gentamicin; p less than 0.05 for piperacillin). Rifampin, erythromycin and TMP/SMZ gave better survival than piperacillin (p less than 0.01). Although ampicillin plus gentamicin were superior to ampicillin alone (p less than 0.01) in reducing the number of organisms in the spleens, rifampin was superior to all regimens in this regard (p less than 0.0005 vs piperacillin, ampicillin, TMP/SMZ; p less than 0.05 vs ampicillin + gentamicin, erythromycin). Rifampin may be a useful addition to other regimens in speeding the elimination of the organism.