Activity of cefotaxime and ceftriaxone alone and in combination with penicillin, ampicillin and piperacillin against neonatal meningitis pathogens.

The activities of penicillin G, ampicillin, piperacillin, cefotaxime and ceftriaxone alone and in combination against 130 isolates of Escherichia coli, group B streptococci and Listeria monocytogenes from neonatal meningitis were assessed by using agar dilution, checkerboard and time-kill techniques. Cefotaxime and ceftriaxone were highly active against E. coli and group B streptococci (MIC90 0.05-0.1 mg/1) but not active against List. monocytogenes. Penicillin G was more active than ampicillin and piperacillin against group B streptococci (MIC90 0.1, 0.12 and 0.24 mg/l respectively) and ampicillin was the most active against List. monocytogenes (MIC90 0.6 mg/l). Every double beta-lactam combination was synergistic for 3-14% of E. coli, 8-26% of group B streptococci and 67-100% of List. monocytogenes in the checkerboard titration. The ceftriaxone combinations were less synergistic than the cefotaxime combinations. In time-kill evaluations using concentrations representative for cerebrospinal fluid, the killing kinetics of E. coli were not influenced by any combination. A significant delay in killing of group B streptococci was observed with penicillin G-cephalosporin and ampicillin-cephalosporin combinations. A significant increased killing of List. monocytogenes was observed with penicillin G-cephalosporin combinations. The other combinations did not alter the killing kinetics of group B streptococci and List. monocytogenes.