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MRSA In The Past Decade

MRSA In The Past Decade. Topics. Microbiology of S.aureus Community-acquired MRSA Vancomycin-resistant MRSA Antibiotic selections Others: MRSA vaccine, nasal carriage and effect of mupirocin. Structure of S.aureus. Panton-Valentine Leukocidin.

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MRSA In The Past Decade

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  1. MRSAIn The Past Decade

  2. Topics • Microbiology of S.aureus • Community-acquired MRSA • Vancomycin-resistant MRSA • Antibiotic selections • Others: MRSA vaccine, nasal carriage and effect of mupirocin

  3. Structure of S.aureus. Panton-Valentine Leukocidin Microbial surface components recognizing adhesive matrix molecules (MSCRAMM)

  4. Comparison of Nosocomial (Health care associated) and Community - Acquired MRSA Bartlett JG. www.medscape;May 2004

  5. 2002

  6. Vancomycin-intermediate S.aureus • 1988 VRE carrying vanA gene reported in France • 1992 In-vitro transfer of vanA determinant from E.faecalis to S.aureus • 1997 First strain of S.aureus with reduced susceptibility to vancomycin and Teicoplanin reported in Japan

  7. Vancomycin-intermediate S.aureus in the United States 1 Smith TL, et al NEJM 1999;340:493-501. 2 Rotunss, et al EID 1999;5:147-9. 3 MMWR 2000;48:1165-7. 4 Unpublished data (CDC, State Health Department) Fridkin SK. CID 2001;32:108-15

  8. Vancomycin-resistant S.aureus • From 1997-present VISA: Japan, U.S., France, U.K., Germany, Korea Hetero-VRSA: Spain, Scotland, Hong Kong, Germany, Netherland, Poland, Greece and Thailand • June 2002, First vanA containing VRSA isolated from a dialysis patient in Michigan, U.S. • August 2002, Second VRSA isolate from Pennsylvania, U.S.

  9. Nomenclature • VISA Vancomycin-intermediate S.aureus • GISA Glycopeptide-intermediate S.aureus • VRSA Vancomycin-resistant S.aureus • hVRSA or hVISA Heteroresistant-VRSA • SA-RVS S.aureus with reduced vancomycin susceptibility

  10. Vancomycin Interpretive Criteria aNCCLS, National Committee for Clinical Laboratory Standards; CA-SFM, Comité de I’Antibiogramme de la Société Française Microbiologie; BSAC, British Society for Antimicrobial Chemotherapy.

  11. Hetero-VRSA • Definition: S.aureus strains that contain subpopulation of vancomycin-resistant daughter cells but for which the MICs of vancomycin for the parent strain are only 1-4 μg/ml. • Identified by growth on BHI screening agar containing vancomycin (4-6 μg/ml), when selected and tested , MICs 2-8 fold higher than original strain. • Population analysis is the standard method of identification (Prototype, Mu3)

  12. Population Analysis Mu50: VRSA, Mu3: hetero-VRSA, H1:MRSA, FDA209P:MSSA

  13. Mechanisms of Vancomycin Resistance • Excess production of peptidoglycan • Reduction of peptidoglycan turnover • Reduction of autolytic activity • Decrease in intracellular glutamine level • Decrease of cross-linkage of peptidoglycan • Abnormal production of murein monomer leading to increased proportion of D-alanyl-D-alanine residues in the peptidoglycan level Still Poorly Understood

  14. Cell wall thickness as a contributor of vancomycin resistance Affinity Trapping & Clogging Phenomenon Hiramatsu K. Lancet Inf Dis 2001;1:127-155

  15. Cell Wall Thickening by Transmission Electron Microscopy Parental MRSA Induced hetero-VRSA

  16. Algorithm for Testing S. aureus with Vancomycin (VA) Acceptable Primary Test Methods Include: April 2004 MIC method1plus VA screen plate (BHIA with 6 µg/ml of VA) Disk diffusion2plus VA screen plate (BHIA with 6 µg/ml of VA) VA zone <14 mm AND GROWTH on VA screen plate VA zone >14 mm AND GROWTH on VA screen plate VA MIC <2 µg/ml And NO growth on VA screen plate VA MIC <2 µg/ml AND GROWTH on VA screen plate (rare) VA MIC >4 µg/ml AND GROWTH on VA screen plate VA zone >14 mm and NO growth on VA screen plate Possible VISA/VRSA Possible VISA/VRSA Report as VSSA3 Report as VSSA3 CHECK purity CONFIRM isolate ID RETEST using non-automated MIC method4 SAVE ISOLATE NOTIFY infection control, physician, local health department and CDC5 of “possible VISA/VRSA” SEND to reference laboratory for confirmation Important Footnotes 1Laboratories using automated susceptibility test methods should add a commercial vancomycin agar screen plate. 2Disk diffusion alone is not sufficient to detect VISA. 3If a laboratory is concerned about a result based on a patient’s history, MIC testing can be performed at CDC. 4 Non-automated methods: reference broth microdilution, agar dilution, agar gradient diffusion (Etest; use a 0.5 McFarland inoculum and Mueller-Hinton agar). 5Report to CDC by email: SEARCH@cdc.gov More VISA/VRSA info: www.cdc.gov/ncidod/hip/vanco/vanco.htm

  17. Alternatives to Vancomycin for MRSA Infection Bartlett JG. www.medscape;May 2004

  18. 100 80 MRSA46 60 MRSA47 MSSA46 40 MSSA47 20 0 AMC SXT FOS OXA TEI CLI ERY GEN PEN VAN แผนภูมิแสดงร้อยละของเชื้อ MRSA และ MSSA ที่ไวต่อยาต้านจุลชีพ ที่ทดสอบ 10 ชนิด ในปี พ.ศ. 2546-47 http://narst.dmsc.moph.go.th

  19. Other Topics • S.aureus bacteremia appear to be of endogenous origin in the nasal mucosa. (Von Eiff C, et al. NEJM 2001;344:11-6) • Prophylactic intranasal application of mupirocin did not significantly reduce S.aureus surgical-site infection rate, but decrease nosocomial S.aureus infections. (Perl TM, et al. NEJM 2002;346: 1871-7) • Bivalent conjugate S.aureus type 5,8 vaccine confered partial immunity. (Shinfield H, et al. NEJM 2002;346:491-6)

  20. Conclusion Nature is always at least ahead of science. • Continuing research on pathogenesis • Future vaccine? • Continuing new drugs development • Prevention is the key. • Need stringent infection control

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