Emergence of linezolid-resistant methicillin-resistant Staphylococcus aureus in Japan

Abstract number: 1733_1314

Hanaki H., Yanagisawa C., Hososaka Y., Ishibashi K., Yamamoto S., Imamura Y., Taniwaki S., Nakae T., Sunakawa K.

Objectives: The linezolid (LZD)-resistant methicillin-resistant Stapylococcus aureus (MRSA) has been reported from USA (8 cases), UK (1), and Brazil (1) yet not from Japan. We isolated the LZD-resistant MRSA from a case of septicaemia patient in June 2006 only four months after LZD had been introduced to clinical use in Japan. Five strains of LZD-resistant MRSA were isolated from the same patient and they were characterised by means of bacteriology and DNA technology.

Methods: Minimum inhibitory concentration (MIC) of antimicrobial agent was determined according to the guideline of Clinical and Laboratory Standard Institutes. Occurrence of the genes encoding staphylococcal cassette chromosome mec (SCC mec), hemolysin (hla, hlb), exofoliative toxin (eta, etb) enterotoxin (sea, seb), toxic shock syndrome toxin-1 (tss, TSST-1), panton-valentain leukocidin (pvl, PVL) and b-lactamase (blaZ) were examined by polymerase chain reaction (PCR). Identity of the strains was verified by pulsed-field gel electrophoresis (PFGE) of the SmaI treated DNA.

Results: MIC of oxacillin, imipenem, pazufloxacin, vancomycin, teicoplanin, arbekacin, minocycline, rifampin, sulfametoxazole/torimetoprim was >128, 64, 1, 1, 4, 16, ≤0.25, and 2 mg/mL, respectively, and that was identical in all five strains. MIC of LZD was highest in the latest isolates of MRSA, 32 mg/mL, though that in all the LZD-unexposed MRSA was 2 mg/mL. SCCmec in all five strains isolated from the patient was type II, which is common in the MRSA in Japan. Chromosomal DNA encoding enterotoxin, heamolysine, and b-lactamase was detected in all the strains, but that was undetectable encoding TSST-1, exofoliative toxin and panton-valentine leukocidin. PFGE of SmaI-treated DNA in all the LZD-resistant MRSAs showed identical DNA profile suggesting the identical origin for all. Only the difference from the DNA profile of the LZD-susceptible strains was that 120 bp band was shifted to 160 bp in the resistant strain.

Conclusion: LZD was licensed in clinical use in Japan since April 2006 as an anti-MRSA drug, and the LZD-resistant MRSA emerged only four months later. LZD was intermittently administered intravenously or orally for 48 days to the patient with MRSA septicaemia, and the LZD-resistant MRSA was isolated from blood on the day the patient passed away. We reported a very first case of LZD-resistant MRSA in Japan and called for precaution for proper use of this powerful antimicrobial agent.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
Back to top