First Report of the Isolation of High-Level Vancomycin-Resistant Enterococcus faecium from a Patient in Japan

Multiple drug-resistant enterococci have become a significant cause of nosocomial infection (9, 11, 12). In particular, there are limited options for the treatment of enterococcal infection caused by high-level glycopeptide-resistant enterococci (9, 11). Infection or colonization by vancomycin-resistant enterococci was first reported in France (10) and the U.K. (14). Since then, vancomycin-resistant enterococci have been reported from many locations throughout Europe (9), the United States, (9), Australia (6, 8), and Argentina (4). In Japan, vancomycin has been used clinically for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections since late 1991. There has been no report describing the isolation of high-level vancomycin-resistant enterococci in Japan (7, 13). We report here the first clinical isolate of high-level vancomycin-resistant Enterococcus faecium in Japan. An 81-year-old woman was hospitalized with acute pyelonephritis and bacteremia with a high fever (40°C) in the internal medicine ward in March 1996. She also had diabetes mellites, hypertension, multiple cerebral infarctions, and neurologic bladder. Escherichia coli was isolated from urine and blood samples. She was treated with cefotiam. Her fever abated 1 week after initiation of therapy. At that time, E. coli was not detected in the blood or urine samples. She received antibiotic therapy for 2 weeks. After completion of the antibiotic therapy, E. faecium was isolated from a follow-up surveillance sample of urine. E. faecium was not isolated in the next urine sample, which was obtained 5 days after the initial enterococci-positive sample. The drug resistance levels (MICs, in micrograms per milliliter) for the E. faecium isolate, named FN1, were as follows: vancomycin, 200; teicoplanin, 50; gentamicin, >1,000; ampicillin, >100; and erythromycin, 100. In addition to being phenotypically VanA (1,2,3), the FN1 plasmid DNAs hybridized with a vanA probe (5), which was a kind gift from P. Courvalin of the Pasteur Institute, Paris, France. The transferability of the vancomycin resistance of FN1 was examined between the donor strain FN1 and the recipient strain E. faecalis FA2-2 (Rifr Fusr) and between FN1 and E. faecium KTRF (Rifr Fusr) by filter-mating experiments. No vancomycin-resistant transconjugants were isolated (frequencies were less than 10−7 per donor cell) in mating experiments. Vancomycin-resistant E. faecium was not identified in stool samples from the patient or from other patients who were hospitalized in the same room. The patient had never received vancomycin chemotherapy. Although the reservoir and mode of infection of the vancomycin-resistant E. faecium was not determined in this case, E. faecium FN1 was the first case of high-level vancomycin-resistant enterococci with a class A phenotype isolated from a human in Japan. This work was supported by a grant for the study of drug-resistant bacteria funded by the Ministry of Health and Welfare, Tokyo, Japan, in 1996 and by a grant from the Ohyama Health Foundation, Inc., Tokyo, Japan. We thank P. Courvalin for providing the M13-vanA probe and E. Kamei for helpful advice on the manuscript.