MRSA In The Past Decade

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MRSAIn The Past Decade
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Topics

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

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Structure of S.aureus.
Panton-Valentine Leukocidin
Microbial surface components recognizing adhesive
matrix molecules (MSCRAMM)
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Comparison of Nosocomial (Health care associated)
and Community - Acquired MRSA
Bartlett JG. www.medscapeMay 2004
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2002
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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

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Vancomycin-intermediate S.aureus in the United
States
1 Smith TL, et al NEJM 1999340493-501. 2
Rotunss, et al EID 19995147-9. 3 MMWR
2000481165-7. 4 Unpublished data (CDC, State
Health Department)
Fridkin SK. CID 200132108-15
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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.

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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

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Vancomycin Interpretive Criteria
aNCCLS, National Committee for Clinical
Laboratory Standards CA-SFM,
Comité de IAntibiogramme de la Société Française
Microbiologie BSAC, British Society for
Antimicrobial Chemotherapy.
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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)

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Population Analysis
Mu50 VRSA, Mu3 hetero-VRSA, H1MRSA,
FDA209PMSSA
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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
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Cell wall thickness as a contributor of
vancomycin resistance
Affinity Trapping Clogging Phenomenon
Hiramatsu K. Lancet Inf Dis 20011127-155
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Cell Wall Thickening by Transmission Electron
Microscopy
Parental MRSA
Induced hetero-VRSA
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Algorithm for Testing S. aureus with Vancomycin
(VA)
Acceptable Primary Test Methods Include
April 2004
Disk diffusion2 plus VA screen plate (BHIA with 6
µg/ml of VA)
MIC method1 plus VA screen plate (BHIA with 6
µg/ml of VA)
VA zone lt14 mm AND GROWTH on VA screen plate
VA zone gt14 mm AND GROWTH on VA screen plate
VA MIC lt2 µg/ml And NO growth on VA screen plate
VA MIC lt2 µg/ml AND GROWTH on VA screen
plate (rare)
VA MIC gt4 µg/ml AND GROWTH on VA screen plate
VA zone gt14 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 patients 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_at_cdc.gov
More VISA/VRSA info www.cdc.gov/ncidod/hip/vanco/
vanco.htm
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Alternatives to Vancomycin for MRSA Infection
Bartlett JG. www.medscapeMay 2004
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http//narst.dmsc.moph.go.th
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Other Topics

• S.aureus bacteremia appear to be of endogenous
  origin in the nasal mucosa.
  (Von Eiff C, et al. NEJM 200134411-6)
• 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 2002346 1871-7)
• Bivalent conjugate S.aureus type 5,8 vaccine
  confered partial immunity. (Shinfield H, et al.
  NEJM 2002346491-6)

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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