Clinical evaluation of a new broad-spectrum oxa-beta-lactam antibiotic, moxalactam, in neonates and infants.
Moxalactam, a new parenteral 1-oxa-beta-lactam antibiotics, is highly effective in vitro against gram-negative enteric bacilli, including isolated from neonates with meningitis. Studies with moxalactam in experimental coliform meningitis demonstrated favorable penetration, bioavailability, and antibacterial activity in CSF. The potential value of moxalactam for therapy of gram-negative enteric meningitis of infancy prompted this study. Pharmacokinetics of moxalactam were determined in 74 infants and serum concentration-time curves were characterized bay the two-compartment open-system kinetic model. The mean peak serum concentration at the end of 50 mg/kg, ten-minute infusions was approximately 125 micrograms/ml. Elimination half-life values correlated inversely with gestational and chronologic age. The mean half-lives were 6.2 hours in neonates less than one week of age, 4.4 hours in those one to 4 weeks, and 1.6 hours in infants one to 24 months of age. A mean CSF penetration of 30% was demonstrated after repeated doses of moxalactam in 11 infants with coliform meningitis. Thirteen neonates and two infants with gram-negative enteric bacillary infections were successfully treated with this agent. the drug was well tolerated and adverse effects were not observed. Moxalactam will be evaluated in a prospective, controlled study of gram-negative enteric meningitis by the Neonatal Meningitis Cooperative Study Group.
D001424:Bacterial Infections / Q000188:drug therapy*; D001922:Brain Abscess / Q000188:drug therapy; D002511:Cephalosporins / Q000378:metabolism*; D002513:Cephamycins / Q000378:metabolism* / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000188:drug therapy; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy*; D007263:Infusions, Parenteral; D007273:Injections, Intramuscular; D007700:Kinetics; D007710:Klebsiella Infections / Q000188:drug therapy; D008297:Male; D008581:Meningitis / Q000188:drug therapy; D009070:Moxalactam; D012480:Salmonella Infections / Q000188:drug therapy; D012706:Serratia marcescens / Q000187:drug effects
D002511:Cephalosporins; D002513:Cephamycins; D009070:Moxalactam