Early synergistic killing activity at concentrations attainable in CSF of amoxicillin or cefotaxime and aminoglycosides against Haemophilus influenzae.

Rapid eradication of bacteria from the CSF is critical for the outcome of Haemophilus influenzae meningitis in children. In 15 patients studied, the mean H. influenzae colony counts in CSF were 10(5) CFU/ml (range: 10(2) to 10(9) CFU/ml). Time-kill curves were determined for amoxicillin and cefotaxime alone and in combination with gentamicin or amikacin, against 60 clinical isolates of H. influenzae at concentrations equivalent to those found in CSF following systemic administration. Against beta-lactamase-negative strains (n = 44) a bactericidal effect was observed at 18 h for amoxicillin alone, at 5 h for amoxicillin plus aminoglycosides and at 2.5 h for cefotaxime with or without aminoglycosides. Against beta-lactamase-positive strains a bactericidal effect was observed at 18 h for cefotaxime, at 5 h for amoxicillin plus aminoglycosides and at 2.5 h for cefotaxime plus aminoglycosides. It appears that despite low concentrations of gentamicin or amikacin in the CSF, the accelerated killing of H. influenzae provides a rationale for the initial use of the combination of cefotaxime and aminoglycosides in the initial treatment of H. influenzae meningitis.