Treatment of experimental Haemophilus influenzae type b meningitis with 1-oxa-beta-lactam (LY127935)

Abstract

1-Oxa-beta-lactam (LY127935) (Shionogi 6059-S) is a new type beta-lactam antibiotic having a broad spectrum of antibacterial activity. It is highly active against ampicillin-resistant strains of Haemophilus influenzae exhibiting minimal inhibitory concentrations as low as 0.06 microgram/ml. This compound also has the ability to penetrate into the cerebrospinal fluid of both normal and infected infant rats and attains approximately 10% of the corresponding blood levels. LY127935 was evaluated for its ability to treat ampicillin-resistant H. influenzae meningitis in an established experimental model using infant rats. Rats with ampicillin-resistant H. influenzae meningitis were treated subcutaneously three times daily for 2 days with various dose levels of LY127935. When given in doses as low as 10 mg/kg, LY127935 sterilized the blood and cerebrospinal fluid in all rats examined at 1 and 5 days posttreatment. In contrast, ampicillin was not effective at this dose in eliminating H. influenzae from the blood and cerebrospinal fluid of infected rats. LY127935 was effective against experimental ampicillin-resistant H. influenzae meningitis in the dosages employed.