ASSESSMENT OF THE SYNERGISTIC INTERACTIONS OF LEVOFLOXACIN AND AMPICILLIN AGAINST ENTEROCOCCUS-FAECIUM BY THE CHECKERBOARD AGAR DILUTION AND TIME-KILL METHODS

Multidrug-resistant enterococci have become increasingly difficult to eradicate in a growing number of nosocomial infections. With the emerg ence of vancomycin-resistant enterococci, the use gf synergistic antib iotic combinations has become one of the only remaining therapeutic op tions. Levofloxacin, the active 1-isomer of ofloxacin, is a new oral a nd intravenous fluoroquinolone with a broad spectrum of activity again st numerous Gram-positive, Gram-negative, and atypical organisms. The in vitro activity of levofloxacin, alone and in combination with ampic illin, against recent clinical isolates of Enterococcus faecium was as sessed for synergistic interactions using the checkerboard agar diluti on technique and time-kill methodology. Against all strains, the stati c technique of checkerboard agar dilution demonstrated indifferent or additive effects for the ampicillin + levofloxacin combination. With t he dynamic time-kill technique, synergy was demonstrated far ampicilli n (16 mu g/ml) + levofloxacin (2 mu g/ml) combination against three le vofloxacin-sensitive, ampicillin-resistant isolates. At 24 h, the comb ination yielded a greater than or equal to 2-log(10) decrease in CFU/m l compared to levofloxacin alone, while ampicillin had negligible effe cts. Against both a levofloxacin-intermediate, ampicillin-resistant is olate, and a highly levofloxacin-resistant, ampicillin-resistant isola te, none of the ampicillin + levofloxacin combinations tested demonstr ated a synergistic interaction. The time-kill method suggested synergy for the ampicillin + levofloxacin combination against some strains of E. faecium. (C) 1997 Elsevier Science Inc.