Effect of ampicillin and chloramphenicol against Haemophilus influenzae

Synergy, determined by isobolograms constructed from the minimal inhibitory concentrations of combinations of ampicillin and chloramphenicol, was observed against six of 13 ampicillin-susceptible Haemophilus influenzae type b isolates and against five of eight ampicillin-resistant strains by using a small inoculum of 10(4) colony forming units (CFU) per milliliter. Synergy occurred against nine of 13 ampicillin-susceptible and against two of eight ampicillin-resistant strains using a large inoculum of 10(7) CFU/ml. When synergy was not observed, additive effects occurred against the remainder of isolates. Additive effects were also observed against single strains of chloramphenicol-resistant, nontypeable H. influenzae and H. parainfluenzae. No antagonism was observed. These data indicate that ampicillin and chloramphenicol may be synergistic against a significant number of H. influenzae strains depending on inoculum size, but the effect is unpredictable for a given isolate. These data support the recommendation that ampicillin and chloramphenicol both be used as initial therapy for patients with suspected bacterial meningitis.