AMPICILLIN-GENTAMICIN SYNERGY IN TREATMENT OF GROUP B STREPTOCOCCAL MENINGITIS

Abstract

Ampicillin and gentamicin in combination accelerate killing of group B streptococci (GBS) in vitro. Penicillin-amlnoglycoside combinations have been recommended for the treatment of GBS meningitis despite poor penetration of the aminogiycosides into the cerebrospinal fluid. Previous studies have demonstrated accelerated killing of GBS by combinations of penicillin or ampicillin and gentamicin. These studies utilized concentrations of amlnoglycosides not consistently attainable in the CSF following systemic administration. We examined 20 strains of GBS for accelerated killing with gentamicin concentrations attainable in the CSF by systemic administration. All strains (Ia, Ib, Ic, II, III) were Isolated from infants with sepsis or meningitis. Preliminary studies revealed that mean MIC's by tube dilution were: penicillin 0.02, ampicillin 0.16, and gentamicin 4.5ugm/ml. No synergy was detected by the checkerboard titration method. Killing kinetics were determined using 10ugm/ml of ampicillin or penicillin alone or in combination with 0.1 or 0.5ugm/ml of gentamicin.Fifteen of the 20 strains demonstrated acceierated killing with gentamicin concentrations comparable to those attained in the CSF. These findings provide a rationale for the use of a combination of a penicillin and gentamicin in treating GBS meningitis in spite of "subtherapeutic" levels of gentamicin in the CSF.