Synergy Between Penicillins and Low Concentrations of Gentamicin in the Killing of Group B Streptococci

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Abstract
Antimicrobial sensitivity, synergy, and timed-killing assays were determined for 20 strains of group B streptococci isolated from cultures of blood and cerebrospinal fluid (CSF) of infected neonates. The mean minimal inhibitory concentrations by the tube-dilution method were as follows: penicillin, 0.02 µg/ml; ampicillin, 0.05 µg/ml; and gentamicin, 4.5 µg/ml. No synergy was detected with any combination of penicillin or ampicillin and gentamicin by the checkerboard titration method. Killing kinetics were determined for combinations of penicillin or ampicillin and gentamicin at low concentrations of these antibiotics comparable to those attained in the CSF following systemic administration of these antibiotics. Addition of 0.1 µg and 0.5 µg of gentamicin/ml to penicillin or ampicillin significantly accelerated the killing of group B streptococci. Despite the “poor” permeation of gentamicin into the CSF, the accelerated killing of streptococci at low concentrations of this antibiotic provides a rationale for the initial use of a combination of penicillinor ampicillin and gentamicin in the treatment of group B streptococcal meningitis.