Efficacy of BMY-28142 in experimental bacteremia and meningitis caused by Escherichia coli and group B streptococci.
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.
D000818:Animals; D000077723:Cefepime; D002439:Cefotaxime / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use*; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D008581:Meningitis / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000627:therapeutic use; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000187:drug effects
D002511:Cephalosporins; D000077723:Cefepime; D002439:Cefotaxime; D010400:Penicillin G