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The combination of vancomycin and beta-lactam antibiotic synergistically is known to act on vancomycin-susceptible Staphylococcus aureus (VSSA). But some MRSA with the antagonism in the combination of vancomycin and beta-lactam antibiotic was identified in Japan. We called the MRSA "beta-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR)", to distinguish it from hetero-VISA. The percentage of hetero-VISA isolated in Japan that Hiramatsu et al. reported in The Lancet in 1997 was that of "candidate-hetero-VISA" because it did not satisfy the criteria for detection of hetero-VISA that they proposed. Therefore, except for Mu3, a strictly defined hetero-VISA strain has never been detected in Japan. However, BIVR is certainly detectable in Japan. We performed a retrospective study of BIVR in 189 MRSA strains isolated from blood between 1978 and 1999 at the same institution. To performed a retrospective study, 189 MRSA strains were divided such as 1978-1984 (45strains), 1985-1989 (45strains), 1990-1994 (49strains), 1995-1999 (50strains). MIC90 of anti-MRSA drugs according to above chronological transition were 2, 2, 2, 1 as vancomycin, 2, 1, 1, 1 as teicoplanin, and 8, 8, 1, 1 microgram/mL as arbekacin, respectively, and then the detection rate of BIVR was 2.2, 2.2, 6.1, 10.4%, respectively. The BIVR detection rate in MRSA isolated from blood at 14 institutions was 14.8% (12/81) in 1999-2002, and that of non-blood was 4.6% (42/905) (p < 0.001; chi 2-t examination). Of particular importance is that the percentage of BIVR isolated from blood is higher than that from non-blood, and the detection rate of BIVR from blood increases annually.

Fuminori Sakai1, Hideaki Hanaki2, Kazunari Barada4, Yuriko Hirao1, Takashi Inamatsu5, Taiji Nakae2, Keisuke Sunakawa31Laboratory of Infectious Diseases, Graduate School of Infection Control Sciences, 2Research Center for Anti-Infectious Drugs, Kitasato Institute, 3Department of Research Project Studies, Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan; 4Department of Pharmacy, General Ota Hospital, Society of Health Insurance of Fuji Heavy Industries Ltd, Gunma, Japan; 5Department of Infectious Diseases, Tokyo Metropolitan Geriatric Hospital, Tokyo, JapanAbstract: We analyzed 218 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from the septicemia patients in a geriatric hospital for 25 years. These strains were classified into 11 major DNA types, A through K, and 27 minor types. The strains belonging to group A and B isolated before 1990 were susceptible to imipenem (IPM), fluoroquinolone, and most other antibiotics tested, except that they were markedly resistant to gentamicin. Strains mostly isolated in 1985 and thereafter were classified into group C through K, and they were mainly resistant to IPM, fluoroquinolones, and clindamycin. Analysis of the MRSA marker gene, staphylococcal cassette chromosome mec (SCCmec), of these strains revealed that the strains in groups A and B had mainly type IV and type I, respectively, and that strains in groups C through J had mainly type II. These results suggested that the strains holding type II SCCmec were resistant to IPM, fluoroquinolone, and clindamycin and they were dominant-resistant type after late 1980s. The antibiotic resistance profiles of MRSA dramatically changed during late 1980s, and these were correlated with the SCCmec types. The lesson from this study would be that consistent execution of surveillance study is needed to update the resistant profiles.Keywords: methicillin-resistant Staphylococcus aureus, DNA typing, antibiotic resistance, survey, geriatric hospital