In-vitro activities of 11 antibiotics against vancomycin-resistant enterococci isolated in Japan

J Antimicrob Chemother 1999; 44: 415–416

Shuichi Miyazaki*, Yoshikazu Ishii, Akira Ohno, Nobuhiko Furuya, Tetsuya Matsumoto, Kazuhiro Tateda and Keizo Yamaguchi

Department of Microbiology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143, Japan

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 USA.1,2 In 1998, Fujita et al.3 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.3 They were stored at -80°C 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 108 cfu/L. The MICs were determined following incubation at 35°C 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 gallinarum (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. faeciumand 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).


View this table:
[in this window]
[in a new window]
 
Table. In-vitro activities of 11 antibiotics against 10 VRE isolated from patients in Japan
 
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. faecium which, in general, are susceptible to fewer agents than those of E. gallinarum. Although our observations are based on only a small number of strains, we have found linezolid to be the most promising drug tested, followed by SCH 27899 and quinupristin/dalfopristin. These findings will need to be confirmed by further studies involving larger numbers of isolates, and clinical trials will be necessary to evaluate the efficacies of the antibiotics as treatment of patients with infections caused by VRE.

Notes

* Corresponding author. Tel:+81-3-3762-4151; Fax:+81-3-5493-5415; E-mail:shuichi{at}med.toho-u.ac.jp Back

References

1 . Murray, B. E. (1990). The life and times of the Enterococcus. Clinical Microbiology Reviews 3, 46–65.[ISI][Medline]

2 . Gordts, B., Van Landuyt, H., Ieven, M., Vandamne, P. & Goossens, H. (1995). Vanvomycin-resistant enterococci colonizing the intestinal tracts of hospitalized patients. Journal of Clinical Microbiology 33, 2842–6.[Abstract]

3 . Ishii, Y., Ohno, A., Kashitani, S., Iwata, M. & Yamguchi, K. (1996). Identification of vanB-type vancomycin resistance in Enterococcus gallinarum from Japan. Journal of Infection and Chemotherapy 2, 102–5.

4 . National Committee for Clinical Laboratory Standards. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fourth Edition: Approved Standard M7-A4. NCCLS, Wayne, PA.

5 . National Committee for Clinical Laboratory Standards. (1998). Performance Standards for Antimicrobial Susceptibility Testing—Eighth Informational Supplement: Approved Standard M100-S8. NCCLS, Wayne, PA.

6 . Barry, A. L., Fuchs, P. C. & Brown, S. D. (1997). Provisional interpretive criteria for quinupristin/dalfopristin susceptibility tests. Journal of Antimicrobial Chemotherapy 39, Suppl. A, 87–92.[Abstract/Free Full Text]

7 . Wise, R., Andrews, J. M., Boswell, F. J. & Ashby, J. P. (1998). The in-vitro activity of linezolid (U-100766) and tentative breakpoints. Journal of Antimicrobial Chemotherapy 42, 721–8.[Abstract]