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 μg/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 10⁶ 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 or life. All animals who received antibiotics had better survival than the controls given saline (p < 0.01 for rifampin, erythromycin, TMP/SMZ, ampicillin, ampicillin + gentamicin; p < 0.05 for piperacillin). Rifampin, erythromycin and TMP/SMZ gave better survival than piperacillin (p < 0.01). Although ampicillin plus gentamicin were superior to ampicillin alone (p < 0.01) in reducing the number of organisms in the spleens, rifampin was superior to all regimens in this regard (p < 0.0005 vs piperacillin, ampicillin, TMP/SMZ; p < 0.05 vs ampicillin + gentamicin, erythromycin). Rifampin may be a useful addition to other regimens in speeding the elimination of the organism.