Assessment of the synergistic interactions of levofloxacin and ampicillin against Enterococcus faecium by the checkerboard agar dilution and time-kill methods

Abstract

Multidrug-resistant enterococci have become increasingly difficult to eradicate in a growing number of nosocomial infections. With the emergence of vancomycin-resistant enterococci, the use of synergistic antibiotic combinations has become one of the only remaining therapeutic options. Levofloxacin, the active l-isomer of ofloxacin, is a new oral and intravenous fluoroquinolone with a broad spectrum of activity against numerous Gram-positive, Gram-negative, and atypical organisms. The in vitro activity of levofloxacin, alone and in combination with ampicillin, against recent clinical isolates of Enterococcus faecium was assessed for synergistic interactions using the checkerboard agar dilution technique and time-kill methodology. Against all strains, the static technique of checkerboard agar dilution demonstrated indifferent or additive effects for the ampicillin + levofloxacin combination. With the dynamic time-kill technique, synergy was demonstrated for ampicillin (16 μg/ml) + levofloxacin (2 μg/ml) combination against three levofloxacin-sensitive, ampicillin-resistant isolates. At 24 h, the combination yielded a ≥2-log 10 decrease in CFU/ml compared to levofloxacin alone, while ampicillin had negligible effects. Against both a levofloxacin-intermediate, ampicillin-resistant isolate, and a highly levofloxacin-resistant, ampicillin-resistant isolate, none of the ampicillin + levofloxacin combinations tested demonstrated a synergistic interaction. The time-kill method suggested synergy for the ampicillin + levofloxacin combination against some strains of E. faecium.