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Unorthodox antibiotic combinations including ciprofloxacin against high-level gentamicin resistant enterococci
M F Tripodi1, R Utili, A Rambaldi
1Institute of Medical Therapy, Second University of Naples, Italy.
Abstract:
Development of high-level gentamicin resistance among enterococci represents a serious therapeutic problem as it precludes synergy between aminoglycosides and cell-wall active agents. As part of a search for active antibiotic combinations against enterococci with high-level gentamicin resistance, we tested by the time kill curve method the efficacy of ciprofloxacin combined with ampicillin, trimethoprim-sulphamethoxazole, vancomycin or teicoplanin against ten isolates of Enterococcus faecium, three of Enterococcus casseliflavus and 13 of Enterococcus faecalis that exhibited a MIC of gentamicin > or = 2000 mg/L. Most of the E. faecium were also resistant to ampicillin and to ciprofloxacin. The combination of ciprofloxacin with ampicillin was bactericidal against five of seven E. faecium strains that exhibited a ciprofloxacin MIC < or = 4 mg/L, but was inactive against the three E. faecium that were highly resistant to ciprofloxacin. This combination was also bactericidal against the E. casseliflavus and all the E. faecalis strains. The combination of ciprofloxacin with trimethoprim-sulphamethoxazole was bactericidal against five of the seven E. faecium and seven of the nine E. faecalis strains with a ciprofloxacin MIC < or = 4 mg/L. No bactericidal activity of this combination was seen against the enterococci that were highly resistant to either ciprofloxacin or to trimethoprim-sulphamethoxazole. The combination of ciprofloxacin with glycopeptides was inactive against E. faecium and E. casseliflavus and against E. faecalis, it was either ineffective or antagonistic; in only one case it was bactericidal. Five strains of E. faecium were resistant to all antibiotic combinations tested.
Insights
High-level gentamicin resistance in enterococci poses a therapeutic challenge. Ciprofloxacin combined with ampicillin or trimethoprim-sulfamethoxazole showed bactericidal activity against resistant enterococci, but efficacy varied with isolate resistance profiles.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- High-level gentamicin resistance (HLGR) in enterococci complicates treatment by preventing synergistic effects with cell-wall active agents.
- Enterococcal infections, particularly those caused by HLGR strains, are a significant clinical concern requiring effective therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of antibiotic combinations against enterococci exhibiting high-level gentamicin resistance.
- To identify active antibiotic combinations for treating infections caused by multidrug-resistant enterococci.
Main Methods:
- Time-kill curve assays were employed to assess the bactericidal activity of antibiotic combinations.
- Ten Enterococcus faecium, three Enterococcus casseliflavus, and 13 Enterococcus faecalis isolates with gentamicin Minimum Inhibitory Concentrations (MICs) ≥ 2000 mg/L were tested.
- Combinations included ciprofloxacin with ampicillin, trimethoprim-sulfamethoxazole, vancomycin, or teicoplanin.
Main Results:
- Ciprofloxacin-ampicillin combination demonstrated bactericidal activity against most E. casseliflavus and E. faecalis strains, and some E. faecium strains with lower ciprofloxacin MICs.
- Ciprofloxacin-trimethoprim-sulfamethoxazole was bactericidal against certain E. faecium and E. faecalis strains, particularly those with lower ciprofloxacin MICs.
- Ciprofloxacin-glycopeptide combinations showed limited or antagonistic activity against most enterococcal isolates.
- Five E. faecium strains were resistant to all tested antibiotic combinations.
Conclusions:
- Ciprofloxacin combined with ampicillin or trimethoprim-sulfamethoxazole can be effective against HLGR enterococci, but resistance to these agents, especially ciprofloxacin, can limit efficacy.
- Treatment outcomes depend on the specific enterococcal species and their susceptibility profiles to the combined antibiotics.
- The emergence of multidrug resistance in enterococci necessitates the continuous search for novel and effective therapeutic strategies.