We evaluated the activity of BMY-28142 against a K1 E. coli strain and a type III group B streptococcal strain in vitro and in vivo and compared the results with those of cefotaxime and penicillin G, respectively. In vitro, the MICs and MBCs of BMY-28142 were close to those of cefotaxime (less than or equal to 2-fold difference) for E. coli and fourfold less than those of penicillin G for group B streptococci. In vivo studies with an experimental bacteremia and meningitis model in newborn rats revealed that the mean penetration of BMY-28142 into the cerebrospinal fluid was 15% that of concomitant levels in serum and that significantly greater bactericidal titers were achieved in blood and cerebrospinal fluid for both test organisms with BMY-28142 than with cefotaxime and penicillin G. However, the overall efficacy of BMY-28142 was similar to that of cefotaxime for the E. coli infection and that of penicillin G for the group B streptococcal infection. This was shown by similar rates of bacterial clearance from blood and cerebrospinal fluid and similar mortality rates. These findings indicate that the activity of BMY-28142 is bactericidal in vitro and in vivo against E. coli and group B streptococci, suggesting that this agent may be a suitable alternative for the therapy of E. coli and group B streptococcal bacteremia and meningitis.