UNORTHODOX ANTIBIOTIC COMBINATIONS INCLUDING CIPROFLOXACIN AGAINST HIGH-LEVEL GENTAMICIN-RESISTANT ENTEROCOCCI

Development of high-level gentamicin resistance among enterococci repr esents a serious therapeutic problem as it precludes synergy between a minoglycosides and cell-wall active agents. As part of a search for ac tive antibiotic combinations against enterococci with high-level genta micin resistance, we tested by the time kill curve method the efficacy of ciprofloxacin combined with ampicillin, trimethoprim-sulphamethoxa zole, vancomycin or teicoplanin against ten isolates of Enterococcus f aecium, three of Enterococcus casseliflavus and 13 of Enterococcus fae calis that exhibited a MIC of gentamicin greater than or equal to 2000 mg/L. Most of the E. faecium were also resistant to ampicillin and to ciprofloxacin. The combination of ciprofloxacin with ampicillin was b actericidal against five of seven E. faecium strains that exhibited a ciprofloxacin MIC less than or equal to 4 mg/L, but was inactive again st the three E. faecium that were highly resistant to ciprofloxacin. T his combination was also bactericidal against the E. casseliflavus and all the E. faecalis strains. The combination of ciprofloxacin with tr imethoprim-sulphamethoxazole was bactericidal against five of the seve n E. faecium and seven of the nine E. faecalis strains with a ciproflo xacin MIC less than or equal to 4 mg/L. No bactericidal activity of th is combination was seen against the enterococci that were highly resis tant to either ciprofloxacin or to trimethoprim-sulphamethoxazole. The combination of ciprofloxacin with glycopeptides was inactive against E. faecium and E. casseliflavus and against E. faeculis, it was either ineffective or antagonistic; in only one case it was bactericidal. Fi ve strains of E. faecium were resistant to all antibiotic combinations tested.