Characterization of Vancomycin-Resistant Enterococcus faecium Isolates from the United States and Their Susceptibility In Vitro to Dalfopristin-Quinupristin

Abstract

In the course of clinical studies with the investigational streptogramin antimicrobial dalfopristin-quinupristin, isolates of vancomycin-resistant Enterococcus faecium were referred to our laboratory from across the United States. Seventy-two percent of the strains were of the VanA type, phenotypically and genotypically, while 28% were of the VanB type. High-level resistance to streptomycin or gentamicin was observed in 86 and 81%, respectively, of the VanA strains but in only 69 and 66%, respectively, of the VanB strains. These enterococci were resistant to ampicillin (MIC for 50% of the isolates tested [MIC50] and MIC90, 128 and 256 μg/ml, respectively) and to the other approved agents tested, with the exception of chloramphenicol (MIC90, 8 μg/ml) and novobiocin (MIC90, 1 μg/ml). Considering all of the isolates submitted, dalfopristin-quinupristin inhibited 86.4% of them at concentrations of ≤1 μg/ml and 95.1% of them at ≤2 μg/ml. However, for the data set comprised of only the first isolate submitted for each patient, 94.3% of the strains were inhibited at concentrations of ≤1 μg/ml and 98.9% were inhibited at concentrations of ≤2 μg/ml. Multiple drug resistance was very common among these isolates of vancomycin-resistant E. faecium, while dalfopristin-quinupristin inhibited the majority at concentrations that are likely to be clinically relevant.

Quinupristin/Dalfopristin Therapy for Infections Due to Vancomycin-Resistant Enterococcus faecium

“…Quinupristin/dalfopristin has a broad spectrum of activity in vitro against gram-positive bacteria, including coagulase-negative staphylococci, methicillinsusceptible and methicillin-resistant Staphylococcus aureus, and multidrug-resistant strains of Streptococcus pneumoniae. Quinupristin/dalfopristin is also active against most vancomycinresistant strains of Enterococcus faecium [24,25]. This activity of quinupristin/dalfopristin against vancomycin-resistant E. faecium is generally bacteriostatic and not bactericidal [25].…”

“…Quinupristin/dalfopristin is also active against most vancomycinresistant strains of Enterococcus faecium [24,25]. This activity of quinupristin/dalfopristin against vancomycin-resistant E. faecium is generally bacteriostatic and not bactericidal [25]. Because of the paucity of available antimicrobial agents with proven efficacy for treatment of infections due to vancomycinresistant E. faecium, we evaluated the efficacy and safety of quinupristin/dalfopristin for treatment of serious infections caused by vancomycin-resistant E. faecium.…”

Synergistic activity of vancomycin and teicoplanin alone and in combination with streptomycin against Enterococcus faecalis strains with various vancomycin susceptibilities

“…The emergence of enterococci demonstrating high level resistance to a broad range of existing antimicrobials (␤-lactams, aminoglycosides, glycopepetides) as well as newer agents such as quinuspristin-dalfopristin and linezolid [4][5][6][7][8][9] has made bactericidal eradication of these organisms problematic and difficult to achieve. Several drug combinations including the newer agents have been evaluated in vitro and in animal models but results of these have varied, ranging from synergy to ineffectiveness [12][13][14][15][16][17][28][29][30][31].…”

“…Recent reports have also shown that E. faecalis carries multiple virulence genes whereas E. faecium carries few or no such virulence genes [4]. The significance of enterococcal infections is increasing and vancomycin-resistant enterococci (VRE) as well as resistance to a broad range of antimicrobial agents including recently developed therapeutic agents (such as teicoplanin, quinupristin-dalfopristin (Q-D) and linezolid) are becoming widespread in many parts of the world [4][5][6][7][8][9]. Such infections require a bactericidal therapy, which is usually obtained only with a synergistic combination of a cell wall active agent (such as a penicillin or vancomycin), plus an aminoglycoside [10,11].…”

Quinupristin-dalfopristin

“…Other important streptococci, such as Streptococcus pyogenes, Streptococcus agalactiae, and the group C and G streptococci, are also susceptible at achievable quinupristin-dalfopristin concentrations. Quinupristin-dalfopristin shows inhibitory activity against most E. faecium strains with or without expression of high-level vancomycin resistance [31]. Quinupristin-dalfopristin inhibited 86.4% of vancomycin-resistant E. faecium isolates at 1 g/mL and 95.1% at 2 g/mL.…”