In vitro susceptibilities of clinical isolates of vancomycin-resistant enterococci.

Recent studies have reported RP59500 (Synercid) (quinupristin-dalfopristin), a semisynthetic streptogramin, to have good in vitro activity against certain enterococcal strains, including vancomycin-resistant strains of Enterococcus faecium (3–5). The purpose of the present study was to determine the in vitro activity of this new compound against a larger sample of resistant strains of enterococci and to compare its activity with those of several currently available antimicrobials. We analyzed 1,044 strains of vancomycin-resistant enterococci (990 E. faecium and 54 E. faecalis) which had been isolated from clinical specimens at 52 New Jersey hospitals between March 1993 and February 1996. Following identification of isolates to species level, MICs were determined by broth microdilution (6). The results are summarized in Table 1. All isolates demonstrated resistance to vancomycin (MIC $ 32 mg/ml); 803 (76.9%) were also resistant to teicoplanin (MIC $ 32 mg/ml). RP59500 had excellent activity against most isolates of E. faecium, with 968 (97.8%) inhibited at a concentration of 1 mg/ml or less, making it the most active agent of those we tested. This supports data obtained in prior studies involving vancomycinresistant E. faecium which have reported a range of MICs from 0.06 to 32 mg,/ml, with MICs at which 90% of isolates are inhibited (MIC90) between 0.5 and 16 mg/ml (2–5, 7). RP59500 was considerably less active against E. faecalis, with only one-third of strains inhibited at 4 mg/ml, an observation consistent with earlier findings (3–5). In addition, the MIC50s and MIC90s of RP59500 for the two species were not affected by differences in the vancomycin resistance phenotype (1). Like that to RP59500, resistance to ampicillin was found to be species specific, with E. faecium (MIC90 $ 128 mg/ml) significantly more likely to be resistant to ampicillin (MIC $ 16 mg/ml) than E. faecalis (MIC90 5 2 mg/ml). High-level resistance to gentamicin, defined by a MIC of .500 mg/ml, was detected in 46 (85.2%) E. faecalis isolates and 586 (59.2%) E. faecium isolates, with the MIC for 517 (81.8%) of these resistant strains being .2,000 mg/ml. Susceptibility to doxycycline was variable; we demonstrated nearly identical biphasic MIC distributions for the two species, with MICs for 723 (69.3%) isolates being #0.25 mg/ml and the remainder of the susceptible strains clustering near the breakpoint (4 to 8 mg/ml). Overall, 724 (73.1%) isolates of E. faecium and 40 (74.1%) isolates of E. faecalis were susceptible (MIC # 4 mg/ml) to doxycycline. The majority of strains tested (89.0%) were highly resistant to ciprofloxacin, with MICs being $32 mg/ml. Only one strain of each species was susceptible (MIC # 1 mg/ml), and 44 (4.4%) strains of E. faecium were intermediate (MIC 5 2 mg/ml). For chloramphenicol, 912 (92.1%) strains of E. faecium and 37 (68.5%) strains of E. faecalis were susceptible (MIC # 8 mg/ml). However, the MIC for the large majority of these susceptible isolates for both species (882 of 949 [92.9%]) was at the breakpoint of 8 mg/ml. These in vitro results, if supported by clinical trials, would confirm the potential of RP59500 as a therapeutic agent in the treatment of E. faecium infections attributed to vancomycinresistant strains. However, its reported lack of bacteriocidal activity against such strains may limit its use in treatment of serious infections (2–5).