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

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Abstract
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/1 respectively) and ampicillin was the most active against List. monocytogenes (MIC90 0·6 mg/1). Every double β-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.