MRSA and VACS: A Unique Opportunity

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MRSA and VACS A Unique Opportunity

• Christopher J. Graber, MD MPH
• Assistant Clinical Professor, David Geffen School
  of Medicine at UCLA
  
• Infectious Diseases Section, VA Greater Los
  Angeles Healthcare System
  
• October 14, 2008

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Staphylococcus aureus A Versatile Pathogen

• Common disease presentations
• Skin and soft tissue infection (SSTI)
• Impetigo
• Cutaneous abscess
• Folliculitis, furuncles, carbuncles
• Cellulitis, erysipelas
• Wound infections
• Pneumonia
• Bacteremia and Endocarditis
• Bone and joint infection
• Urinary tract infection

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Methicillin Resistance in S. aureus A Community
Epidemic
Carleton HA, et al, JID 2004 Diep BA, et al, JID
2006
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The HIV-Infected Patient A Particular Target for
CA-MRSA Infection?

• HIV patients previously demonstrated to be at
  high risk for S. aureus disease in general
  
• Several small clinic-based cohort studies have
  noted dramatic increase in MRSA infections in
  HIV during the CA-MRSA epidemic
  
• No clear relationship between risk of MRSA
  infection and immune status
  

Crum-Cianflone NF, et al, Int J STD AIDS 2007
Skiest D, et al, HIV Med 2006 Shastry L, et al, A
rch Intern Med 2007 Anderson EJ, et al, JAIDS 200
6 Lee NE, et al, CID 2006
Krumholz HM, et al, AmJMed 1989
Stroud L, et al, ICHE 1997 Senthilkumar A, et al,
CID 2001 Mathews WC, et al, JAIDS 2005 Szumowsk
i JD, et al, AAC 2007
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Two Emerging Threats in CA-MRSA in HIV
Multi-Drug Resistance and Frequent Recurrence

• Review of 62 patients presenting with their first
  episode of CA-MRSA SSTI from 2002 through 2006
  
• 71 of patients experienced SSTI recurrence at a
  median of 4.5 months
  
• Decr. susceptibility to clindamycin and
  doxycycline among MRSA isolated at time of
  recurrence

• Plasmid-mediated resistance to mupirocin,
  clindamycin, tetracycline among HIV MSM with
  MRSA infection in SF and Boston

Diep BA, et al, Ann Intern Med 2008
Graber CJ, et al, JAIDS 2008
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Why VACS is Unique for the Study of MRSA

• Time period of enrollment parallels the CA-MRSA
  epidemic
  
• No prior study has compared the burden of MRSA
  disease among HIV to a similarly matched
  population of HIV-
  
• No prior study has been able to compare risk
  factors for MRSA infection in HIV versus HIV-
  
• Behavioral data collected within VACS offers
  opportunity to explore otherwise
  difficult-to-analyze risk factors
  
• Nationwide nature of study allows further insight
  into the regional variation that has
  characterized the CA-MRSA epidemic
  

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MRSA in VACS Preliminary Study

• Review of all MRSA cultures from 6 sites (LA,
  ATL, HOU, WAS, BAL, NYH) over 18mo time period in
  2006-7 to determine types of infection and
  location of SSTI
• Median age of those with MRSA infection identical
  to overall cohort
  
• 49y in HIV
• 50y in HIV-
• Median CD4 count in HIV with MRSA (324) also
  similar to overall cohort

Graber CJ, Gibert CL, Rimland D,
Rodriguez-Barradas MC, Goetz MB, Simberkoff M,
Oursler KK, Justice AC, ICAAC-IDSA 2008
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MRSA Infection in VACS, 2006-7 HIV vs. HIV-,
All Sites
Incidence HIV 30.6/1000 person-yrs (4.6 of c
ohort) HIV- 10.5/1000 person-yrs (1.6 of coho
rt)
IRR 2.9 p21 repeat infections in HIV
2 repeat infections in HIV-
OR 4.3, p0.04
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MRSA Infections By VACS Site, HIV Status
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Sites of MRSA SSTI By HIV Status
OR 3.0, p0.023
OR 0.12, p0.0005
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Goals for Further StudyIncidence and Risk
Factor Analysis

• Determine incidence of S. aureus disease through
  the rise of the CA-MRSA epidemic (2002-8)
  classified by
  
• Methicillin (and other antibiotic) resistance
• Severity of disease
• Type and site of infection
• Community vs. hospital onset
• Focus on community-onset MRSA SSTI to determine
  demographic, clinical, and behavioral risk
  factors for infection in HIV compared to HIV-
  

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Determination of Risk Factors for Community-Onset
MRSA SSTI

• Case-control study where each patient with a
  first community-onset MRSA SSTI is matched to two
  controls w/o h/o of MRSA by
  
• HIV status
• VACS site
• Date of VACS enrollment and most recent VACS
  followup survey completion (must not have
  infection potentially c/w S. aureus in the year
  following survey completion)

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Risk Factors To Be Explored

• Demographic Factors
• Age, race, ethnicity
• Clinical Factors
• CD4 count, HIV viral load, no TMP-SMX prophylaxis
  (HIV)
  
• Diabetes, chronic liver or renal disease
• Behavioral Factors
• Injection drug, illicit stimulant, alcohol,
  tobacco use
  
• Risky sexual behavior, MSM status

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Data Collection(all done centrally at West Haven)

• Step 1 Incidence Determination
• Search of microbiology records of VACS patients
  for Staphylococcus aureus (anticipate 450
  unique cultures)
  
• Review (by me) of progress notes from the time of
  culture to determine
  
• true infection vs. colonization
• uncomplicated vs. complicated disease
• type/site of infection
• community vs. hospital onset

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Data Collection (cont.)

• Step 2 Data for all incident S. aureus infection
  (250 pts) among HIV
  
• CD4, HIV VL, TMP-SMX prophylaxis at/near time of
  infection
  
• Step 3 Selection of controls for community-onset
  MRSA SSTI risk factor analysis (400 pts)
  
• Date of enrollment, survey f/u of eligible
  patients, then review progress notes in the
  following year to determine whether pt had any
  infection potentially caused by S. aureus

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Data Collection Steps

• Step 4
• Collection of demographic, clinical, and
  behavioral data (contained mostly within VACS
  surveys) for both cases and controls

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