Susceptibility of Escherichia coli K1 to four combinations of antimicrobial agents potentially useful for treatment of neonatal meningitis.

The synergy of four combinations of antimicrobial agents potentially useful in the treatment of neonatal meningitis was examined with 19 strains of Escherichia coli K1. The effect on antimicrobial activity of changes in E. coli concentration and in pH to values similar to those of cerebrospinal fluid from infected neonates was also assessed. The degree of synergy, assessed by checkerboard agar dilution of the antimicrobial agents in combination with gentamicin, decreased in the following order: trimethoprim, cefamandole, ampicillin, and chloramphenicol. Significant variation in activity against different strains of E. coli was not observed. In broth dilution tests, the individual antimicrobial agents, but not the combinations, were notably less active at pH 7.00 with an inoculum of 10(7) cfu/ml than at pH 7.40 with 10(5) cfu/ml. Bactericidal activities of the beta-lactam and trimethoprim combinations were similar. Chloramphenicol antagonized the bactericidal effect of gentamicin and of ampicillin plus gentamicin.