Comparative Evaluation of Aztreonam in Therapy for Experimental Bacterial Meningitis and Cerebritis

Aztreonam (SQ 26,776), a new monocyclic β-lactam agent, was compared with several frequently used antibiotics in therapy for three types of experimental meningitis in rabbits and for experimental Escherichia coli cerebritis in rats. Aztreonam was highly active against common gram-negative meningeal pathogens in vitro (all minimal bactericidal concentrations ≤0.125 μg/ml), including ampicillin-sensitive and ampicillin-resistant strains of Haemophilus influenzae, E. coli, and meningococci. In both rabbits and rats, serum concentrations of all antibiotics evaluated closely approximated concentrations found in humans receiving standard parenteral regimens. The percent penetration of aztreonam into purulent rabbit cerebrospinal fluid was 23%. In experimental meningitis, aztreonam was more rapidly bactericidal than amplicillin in meningitis due to ampicillin-sensitive H. influenzae, than ampicillin or chloramphenicol in meningitis due to ampicillin-resistant H. influenzae, and than gentamicin in meningitis due to E. coli. Aztreonam also reduced concentrations of E. coli in rat brain as rapidly as did gentamicin during therapy for experimental cerebritis, the early stage of brain abscess formation.