The pharmacokinetics and bacteriologic efficacy of four beta-lactam antibiotics were studied in the serum and cerebrospinal fluid (CSF) of rabbits using two test strains, Escherichia coli type K1 and group B Streptococcus type III, and 24 gram-positive isolates. Although moxalactam, cefotaxime, cefoperazone, and rocephin are active in vitro against gram-negative bacilli, the gram-positive bacteria Listeria monocytogenes and Streptococcus faecalis were resistant to all four drugs; group B streptococci were resistant to moxalactam. In rabbit CSF, moxalactam had the greatest concentration and penetration, but rocephin had the longest half-life and duration of bactericidal activity. These two drugs were most effective in the CSF of E. coli K1-infected rabbits. Except for moxalatam, the four drugs were comparable to ampicillin in reducing counts of group B Streptococcus type III in CSF. Drug accumulation in CSF and appreciable bacterial killing were observed in E. coli K1-infected animals give moxalactam either periodically or by constant infusion.
Moxalactam (LY127935) is a 1-oxa-,8-lactam which was active in vitro against the majority of 128 strains of gram-negative enteric bacilli isolated from meningitis in neonates. Pharmacokinetics and bacteriological efficacy of LY127935 were studied in a lapin meningitis model. The average penetration of this investigational oxa-cephalosporin into cerebrospinal fluid of infected rabbits was 23% compared with 25% for netilmicin and 11% for ampicillin. The (1,4,7,(10)(11)(12)16) with five strains of gram-negative bacteria isolated from the CSF of neonates with purulent meningitis.MATERIALS AND METHODS Susceptibility studies. In vitro susceptibilities of 128 gram-negative enteric bacilli to LY127935, netilmicin, and ampicillin were determined by an agar dilution method with Mueller-Hinton agar and an inoculum of approximately 5 x 104 colony-forming units (CFU) delivered by the Steers-Foltz replicating device in a volume of 0.001 to 0.002 ml (6,15
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