[Evaluation of the bactericidal curves of beta-lactam and aminoglycoside combinations at the concentrations obtained in the cerebrospinal fluid in Haemophilus influenzae meningitis].

The prognosis and sequelae of patients with Haemophilus influenzae meningitis were related to concentrations of bacteria in the cerebrospinal fluid (CSF). Rapid bacterial killing and rapid reduction of organisms in vivo in CSF are critical to the outcome. In our patients colony counts of Haemophilus influenzae in CSF were 10(2)/ml - 10(9)/ml (mean 10(5)/ml). Killing kinetics were determined for amoxicillin and cefotaxime, alone and in combination with amikacin, against 35 clinical strains of Haemophilus influenzae (43% beta-lactamase-positive) at concentrations of these antibiotics comparable to those attained in the CSF following systemic administration. Antibiotics concentrations were: amoxicillin: 5 mg/ml, cefotaxime: 3.8 mg/l, amikacin: 1.8 mg/l. Mean killing curves with beta-lactamase-negative strains showed that a bactericidal effect was observed at 18 h for amoxicillin, at 5 h for cefotaxime, at 5 h for amoxicillin plus amikacin and at 2 h 30 for cefotaxime plus amikacin. Against beta-lactamase-positive strains a bactericidal effect was observed at 5 h for cefotaxime, at 2 h 30 for cefotaxime plus amikacin and at 18 h for amoxicillin plus amikacin. The finding of significantly increased killing rates of Haemophilus influenzae by amikacin at low concentration in the presence of either ampicillin or cefotaxime suggests that combined therapy may be beneficial in the treatment of meningitis caused by Haemophilus influenzae.