415-420 Corres

Sir, Since the initial reports of vancomycin-resistant enterococci (VRE) in the late 1980s, increasing numbers of such isolates have been identified in centres in both Europe and the U S A . , 2 In 1998, Fujita et al. were the first authors in Japan to describe the isolation of a vancomycin-resistant strain of Enterococcus faecium from a patient with a urinary tract infection. To date, 10 strains of VRE have been isolated from patients in Japan. This finding confirms that the problem is a global one and highlights the need for novel antimicrobials active against these pathogens. The present study was undertaken to evaluate the in-vitro activities of 11 antibiotics against the 10 VRE strains isolated in Japan. The 10 non-replicate VRE isolates were recovered from the following specimens in hospitals across Japan between December 1997 and August 1998: urine (five), blood (three), amniotic fluid (one) and an abscess (one). The isolates were identified by standard laboratory techniques and their genotypes were determined by a polymerase chain reaction (PCR) method described previously. They were stored at –80oC until ready for use. The antibiotics evaluated were as follows: vancomycin (Shionogi & Co., Osaka, Japan), teicoplanin (Hoechst Marion Roussel, Tokyo, Japan), the novel everninomycin, SCH 27899, and gentamicin (Schering-Plough KK, Osaka, Japan), clarithromycin (Taisho Seiyaku, Tokyo, Japan); quinupristin/dalfopristin (Rhone-Poulenc Rorer, Tokyo, Japan); arbekacin (Meiji Seika KK, Tokyo, Japan), minocycline (Lederle Japan, Tokyo, Japan), imipenem (Banyu Pharmaceutical Co., Tokyo, Japan), ampicillin (Sigma Chemical Co., St Louis, MO, USA) and the novel oxazolidinone, linezolid (Pharmacia & Upjohn, Tokyo, Japan). MICs were determined by a microbroth dilution method. The medium used was cation-adjusted Mueller–Hinton broth (Difco, Detroit, MI, USA) supplemented with 5% lysed horse blood and the inoculum was 10 cfu/L. The MICs were determined following incubation at 35oC for 18 h. Six of the 10 isolates were identified as E. faecium (four of which expressed the VanA phenotype and two the VanB phenotype) and the remaining four as Enterococcus galli narum (all expressing the VanC phenotype). Although strains belonging to the latter species exhibit intermediate susceptibility to vancomycin and are not, therefore, resistant in the strictest sense, for the purpose of the present study they have been regarded as VRE. The susceptibility test results for the 10 isolates are summarized in the Table. Of the 11 antibiotics evaluated, linezolid was the only one to which all 10 strains were susceptible. Quinupristin/dalfopristin was the next most active drug, with seven strains being categorized as susceptible. Although breakpoints for SCH 27899 had not been published at the time the study was undertaken, thereby precluding the assigning of susceptibility categories, the MICs for eight isolates were <0.5 mg/L and, for the remaining two isolates, 4 mg/L. Predictably, the strains expressing the VanA phenotype were uniformly resistant to teicoplanin, whereas those expressing the VanB or VanC phenotype were uniformly susceptible. For most of the antibiotics evaluated, there were marked differences between the E. faecium and E. gallinarum strains in terms of their susceptibility patterns. All six of the E. faecium strains were susceptible to quinupristin/dalfopristin, compared with only one of the E. gallinarum strains. On the other hand, all of the latter but none of the former were susceptible to imipenem and ampicillin. In addition, three of the four E. gallinarum strains were susceptible to clarithromycin, compared with only one of the E. faecium strains, and all four E. gallinarum strains exhibited low-level resistance to gentamicin, compared with only two E. faecium strains. Breakpoints for arbekacin were not available, but the MICs of this aminoglycoside for all of the E. gallinarum isolates were 4 mg/L, while those for the E. faecium isolates ranged from 8 to 128 mg/L. Less marked differences were observed with minocycline (two of four E. gallinarum and one of six E. faecium strains being susceptible) and SCH 27899 (MICs < 0.5 mg/L for the four E. gallinarum isolates and four of six E. faecium isolates). It is apparent from the results of this study that the number of antibiotics, either currently available or in various stages of development, with in-vitro activity against VRE is limited. This applies particularly to isolates of E.