Synergistic action of nafcillin and ampicillin against ampicillin-resistant Haemophilus influenzae type b bacteremia and meningitis in infant rats

Infant rats with bacteremia and meningitis induced by ampicillin-resistant Haemophilus influenzae type b were treated with ampicillin and nafcillin, alone or in combination. Neither ampicillin alone (in 19 animals) nor nafcillin alone (in 20 animals) sterilized the blood or cerebrospinal fluid of any treated infant rat. When the combination of ampicillin and nafcillin was used, blood cultures were negative in 18 of 19 infant rats, and cerebrospinal fluid cultures were sterile in 15 of 19 when cultured 30 h after initiation of treatment. In vitro results demonstrated definite synergism between ampicillin and nafcillin against ampicillin-resistant H. influenzae type b. The study suggests that such synergism also exists in vivo.