In vitro antibiotic synergy against Flavobacterium meningosepticum

F. meningosepticum is an unusual, highly antibiotic resistant, gram negative bacillus associated with neonatal meningitis and nursery outbreaks. Optimal therapy is unknown. We successfully treated three neonates with intravenous vancomycin (V) and rifampin (R). The in vitro activity of V and R, meropenem (M), ciprofloxacin (C), alone and in combination, against 4 isolates of F. meningosepticum was performed on 4 isolates from neonates with sepsis and meningitis. MIC's were determined by tube dilution, and fractional inhibitory concentrations (FIC) were calculated by checkerboard microtiter dilution technique. Plates were incubated for 18 hours with final inoculum of 1-3 × 10⁵ cfu using Mueller-Hinton broth. The MIC values for V, R, M and C tested alone were between 16-32, 0.25-1.56, 16, and 0.12-0.5 μg/ml, respectively. FIC results were defined as: <0.5 synergy, 0.5≤1 additive, >1-2 indifferent, >2 antagonistic. FIC results: Organism V+R V+C M+C M+R M+V Case 1 .39 .62 1 1 3 Case 2 .63 .75 .75 1 5 Case 3 .49 .75 1 .63 9 Case 4 42 .62 1 1 5 Synergy was observed between R + V in three isolates, while V + C showed additive effect in all isolates. These results support the clinical evidence that V and R are an appropriate regimen for neonatal meningitis due to F. meningosepticum. M + V were antagonistic, and this combination should be avoided. The clinical efficacy of V plus C or newer quinolones deserves further study.