Chloramphenicol kills Haemophilus influenzae more rapidly than does ampicillin or cefamandole

The bactericidal effects of chloramphenicol and three beta-lactams (ampicillin, cefamandole, and penicillin G) were measured for 27 strains of Haemophilus influenzae type b isolated from the blood or cerebrospinal fluid of infected infants. Of the ampicillin-susceptible strains, 75% were killed by less than 2.0 micrograms of each antibiotic per ml; however, the concentration of the beta-lactam agents required for bactericidal activity was higher than that required for inhibitory activity. Chloramphenicol was the only agent which had no marked discrepancy between inhibitory and bactericidal concentrations regardless of beta-lactamase production. Importantly, chloramphenicol was more rapidly bactericidal than either ampicillin or cefamandole. The bactericidal requirement of ampicillin was increased by the presence of chloramphenicol for about one-third of the isolates examined. Neither the inhibitory nor the bactericidal activity of chloramphenicol was influenced by ampicillin. Synergy occurred for only two beta-lactamase-positive isolates. The more rapid bactericidal action of chloramphenicol persisted even in the presence of ampicillin. The rapid bactericidal action of chloramphenicol with or without ampicillin supports the use of chloramphenicol alone or with ampicillin for H. influenzae infections.