Unorthodox antibiotic combinations including ciprofloxacin against high-level gentamicin resistant enterococci

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.

In vitro activity of multiple antibiotic combinations against Nocardia: relationship with a short‐term treatment strategy in heart transplant recipients with pulmonary nocardiosis

“…The in vitro evaluation of antibiotic combinations was performed by the time‐kill method, as described previously (22), on stored isolates after patient presentation. Briefly, an inoculum of approximately 1 × 10 6 CFU/mL, adjusted from an overnight culture in blood agar, was added to glass tubes containing 5 mL of MHBII and incubated in a shaking air incubator at 37°C for 72 h with each antibiotic alone or in combination, or without antibiotics as a control.…”

“…Using the time‐kill method, we assessed the activity of linezolid, amikacin, imipenem, piperacillin/tazobactam, moxifloxacin, and cotrimoxazole, alone or in combination. The antibiotics were used at concentrations (mg/L) achieved in human serum during treatment: linezolid, 20; amikacin, 38; imipenem, 43; piperacillin–tazobactam, 200; moxifloxacin, 4.3; and cotrimoxazole, 3.4/17 (22).…”

Characterization of Dihydrofolate Reductase Genes from Trimethoprim-Susceptible and Trimethoprim-Resistant Strains of Enterococcus faecalis

“…Renewed interest in old and new antimicrobial agents active against multidrug-resistant microorganisms has emerged in recent years. Recent reports showed a bactericidal effect of trimethoprim-sulfamethoxazole in combination with ciprofloxacin against Enterococcus faecalis and Enterococcus casseliflavus strains (48). Moreover, such a combination has been reported to cure two patients with endocarditis caused by highly gentamicin-resistant E. faecalis strains (39,49).…”

Comparative Activities of Isepamicin, Amikacin, Cefepime, and Ciprofloxacin Alone or in Combination with Other Antibiotics Against Stenotrophomonas maltophilia

“…We used breakpoints specific for Pseudomonas aeruginosa as there are currently no approved breakpoints available for Stenotrophomonas maltophilia. Time-kill studies were performed as previously described, using an inoculum of approximately 1!10 6 cfu/ml [6]. We evaluated the activity of ciprofloxacin, isepamicin, amikacin, cefepime, ceftazidime, ticarcillin-clavulanate, piperacillintazobactam, and trimethoprim-sulfamethoxazole alone or in combination.…”