Colonization and Decolonization of MRSA Rate

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					   Colonization and
Decolonization of MRSA
Ed Septimus, MD, FIDSA, SHEA, FACP
  Carriage of S. aureus as a Risk
        Factor for Infection
• Surgery
  -50 infections in 628 carriers
   33 infections in 2962 noncarriers
   RR 7.1 (4.6-11) Clin Microb Rev 1997; 10:505
  -Orthopedics ICHE 2000; 21:319
  -Cardiac J Infect Dis 1995; 171:216
  Carriage of S. aureus as a Risk
        Factor for Infection
• Hemodialysis
  -S. aureus most frequent infection at
  vascular site or bacteremia
  -Patients on hemodialysis have ↑ S.
  aureus carriage rate
  -Most S. aureus infections are
  endogeneous RR 1.8-4.7 if a carrier
ICHE 1994; 15:78
Am J Kidney Dis 1986; 2:281
   Carriage of S. aureus as a Risk
         Factor for Infection

  -S. aureus leading cause of CAPD related
   -S. aureus nasal carriage is the major risk
   factor RR 1.8-14

Clin Microbiol Rev 1997; 10:505
Perit Dial Int 1996; 16:352
  Carriage of S. aureus as a Risk
        Factor for Infection
• HIV-Positive Patient
  -Increased rate of S. aureus bacteremia
  -Nasal carriage is the most important risk
  factor OR 5.1 Ann Intern Med 1999; 130:221
  -Higher carriage rate of S. aureus with
  progressive HIV (asymptomatic 23.5%;
  AIDS 50%) Eur J Clin Microbiol Infect Dis 1992; 11:985
 Carriage of S. aureus as a Risk
       Factor for Infection
• Intravascular Device-Associated
  -Patients with an IV device who are
  colonized with S. aureus have a higher
  rate of S. aureus bacteremia RR 12.4 Am J
 Med 1996; 100:509

 -Nasal carriage of S. aureus was identified
 by molecular studies to be the source of
 line related bacteremia N Engl J Med 2001; 344:11
   Colonization, Fomites, and Virulence:
Rethinking the Pathogenesis of CA-MRSA Infection
               Clin Infect Dis 2008; 46:752

 • CA-MRSA nasal colonization is uncommon;
   therefore indicating a role for noncolonization
   route for CA-MRSA transmission
 • “Five Cs” of CA-MRSA transmission
   -contact (direct skin-skin contact)
   -compromised skin integrity
   -contaminated objects and environment
   -crowded living
   Factors that Facilitate Transmission

           Crowding                        Frequent Contact


                   Contaminated Surfaces
Compromised Skin     and Shared Items      Cleanliness
   Colonization, Fomites, and Virulence:
Rethinking the Pathogenesis of CA-MRSA Infection
             Clin Infect Dis 2008; 46:752
 Epidemiology MSSA and MRSA
   1. Humans are the natural reservoirs for S.
        aureus. 20-50 % of healthy adults are
      colonized with S. aureus, and 10-20% are
     persistent carriers. Colonization rates are
    highest among patients with type 1 diabetes,
     IV drug users, hemodialysis, dermatologic
                conditions, and AIDS.
2. Colonized and infected patients are the major
                 reservoir of MRSA.
            Epidemiology continued

3. Nasal colonization with MRSA is the single
   most important determinant of subsequent
   MRSA infections
4. Patterns of carriage:
        persistent              20% (12-30%)
        intermittent            30% (16-70%)
        non-carriage            50% (16-69)

J Clin Microbiol 1999;37:3133
         Epidemiology continued
5.Persistent carriers have higher S. aureus
  loads and a higher risk of acquiring S.
  aureus infection Antimicrob Agents Chemo 1963; 161:667
                         J Clin Microbiol 1999; 37:3133

6.Nasal carriers who are also perineal
  carriers have higher S. aureus loads and
  disperse more S. aureus ICHE 2002; 23:495
Role of Nasal Carriage in
  S. aureus Infections
  Lancet Infect Dis 2005; 5:751
            Frequency of MRSA Colonization
                at Various Body Sites




Hill RLR et al. J Antimicrob Chemother 1988;22:377
Sanford MD et al. Clin Infect Dis 1994;19:1123
Evaluation of a Strategy of Screening
Multiple Anatomic Sites for MRSA at
 Admission to a Teaching Hospital
     Infect Control Hosp Epidemiol 2006; 27:181-184

         Site                   % Positive

       Nares                                 73
       Rectum                                47
        Axilla                               25
     Nares+Axilla                            83
     Nares+Rectum                            91
 S. Aureus Intestinal Colonization Associated
with Increased Frequency of S. aureus on Skin
           in Hospitalized Patients
           BMC Infect Dis 2007; 7:105
  Epidemiology of S. aureus Colonization in
         Nursing Home Residents
            Clin Infect Dis 2008;46: May 1
• 14 community NH in MI from March 2003 to
  November 2004
• To assess colonization with S. aureus cultures
  were obtained from nares, oropharynx, PEG site
  insertion (if present), groin, perianal, and
  wounds (if present)
• Residents with a urinary catheter, a PEG, or
  central line were enrolled as the device group
• An equal number of control residents without
  devices were randomly selected as controls
Epidemiology of S. aureus Colonization in Nursing
                Home Residents
             Clin Infect Dis 2008;46: May 1
Throat Swabs Are Necessary to Reliably
      Detect Carriers of S. aureus
              Clin Infect Dis 2007; 45:475

• Samples were obtained from anterior nares and
  pharynx using separate swabs (2000-2005)
• For culture, a selective enrichment broth was
• After overnight incubation, broth was subcultured
  onto both chromogenic agar for S. aureus and
  Columbia agar
• 37.1% of persons were nasal carriers and 12.8%
  were solely throat carriers
• The additional throat swab increased yield from 37%
  to almost 50%
• 0.74% were MRSA positive
          Eradication of MRSA

•   Systemic antimicrobials
•   Topical intranasal mupiricin
•   Bathing with CHG
•   Combination therapy

What sites of MRSA colonization should
 be targeted and does it work?
               General Comments
• Short-term eradication generally successful, but
  most patients become recolonized later with
  same strain Arch Intern Med 1994; 154:1505
• Most regiments seem to last up to 90 days;
  therefore decolonization rather than eradication
  is a better term Clin Infect Dis 2007; 44:186
• Recolonization rates at 1 year approach 50% for
  healthy HCW and 75% for patients on PD
•   Cochrane Database Syst Rev 2003;4
    J Kidney Dis 1993; 22:708
• Recolonization rate at 4 months in patients on
  HD was 56% and recolonization rate was 71% in
  HIV-positive patients ASAIO J 1995; 41:127
    J Infect Dis 1999; 180:896
 Impact of Universal IP Surveillance and
Decolonization on Rates of HA-MRSA BSI
               2006 IDSA Abstract # 142

• Nasal PCR MRSA surveillance for all inpatients
• Five-day mupiricin/CHG decolonization for carriers
• In two-year pre-intervention HA-MRSA BSI was 0.57
  and 0.5 per 1000 admissions respectively
• Post intervention rate HA-MRSA BSI was 0.2 per
  1000 admissions (P=0.02)
• BSI rate for other organisms in the two-year pre-
  intervention was 0.9 and 0.63 per 1000 admissions
  and 0.63 per 1000 admissions post intervention
Reduction in Incidence of Nosocomial MRSA
 Infection in an ICU:Role of Treatment with
Mupiricin Ointment and CHG Baths for Nasal
              Carriers of MRSA
                ICHE 2006; 27:185
 Select Use of Intranasal Mupiricin and CHG
     Bathing and the Incidence of MRSA
Colonization and Infection Among ICU Patients
                ICHE 2007;28:1155
Effectiveness of CHG Bathing to Reduce Catheter-
    Associated Bloodstream Infections in MICU
              Arch Intern Med 2007; 167:2073
  Randomized Controlled Trial of CHG for
 Washing, Intranasal Mupiricin, and Rifampin
and Doxycycline Versus No Treatment for the
     Eradication of MRSA Colonization
             Clin Infect Dis 2007; 44:178
•   Increased mupiricin use has been associated with
    increased drug resistance and failure to clear S.
    Diagn Microbiol Infect Dis 2002; 42:283

•   ASC in SICU for MRSA were tested for mupiricin
    resistance-13.2% were resistant despite low-level
    in-hospital use
    Clin Infect Dis 2007; 45:541

•   Mupiricin resistance noted in 24% of isolates and an
    additional 5% after treatment
    Clin Infect Dis 2007; 44:178

•   Frequent adverse effects of systemic antimicrobial
    therapy with 25% of patients developing GI side
    effects and 5% discontinuing therapy
    Clin Infect Dis 2007; 44:178

•   Risk of development of drug resistance especially
    with rifampin Antimicrob Agents Chemother 1993; 37:1334
 S. aureus carriage and risk of
     surgical site infections
• Nasal carriage of S. aureus has been
  consistently identified as a risk factor
  for development of postoperative
  surgical site infections in a large
  number of studies involving different

 Colbeck JC et al. Can Serv Med J 1959; 15: 326-331
 Weinstein HJ. New Engl J Med 1959; 260: 1303-1308
 Williams REO et al. Br Med J 1959; 2: 658-662
Guidelines for Prevention of
Surgical Site infections (SSI),
Infect Control Hosp Epidemiol 1999; 20:247

  No recommendation to
  preoperatively apply mupirocin
  to nares to prevent SSI-
  unresolved issue
Randomized Trial of Prophylactic Mupiricin + CHG
                      N Engl J Med 2002;346:1871

• Nasal carriage of S. aureus eliminated in
  83.4% v. 27.4% in placebo (p<0.001)
• SSI 7.9% v. 8.5% (ns)
• S. aureus SSI 2.3% v. 2.4% (ns)
• In carriers:
  -any HA staph infection (most SSI) 4% v. 7.7% (OR 7.7% 95% CI 0.25-
  -84.6% PFGE match between nares and SSI
  • All surgical procedures combined-overall
    infection rate low
Antibiotic Prophylaxis in Cardiac
         Surgery, Part II
   Society of Thoracic Surgeons (STS)
                February 2007

Routine mupirocin administration is
 recommended for all patients undergoing
 cardiac surgical procedures in the
 absence of a documented negative testing
 for Staphylococcal colonization (Level A)
 Intranasal Mupiricin Reduces Sternal
Wound Infect after Open Heart Surgery
     in Diabetics and Nondiabetics
         Ann Thorac Surg 2001; 71:1572

• Prospective study over a 3 year period
  who were enrolled in two consecutive
  prospective groups involving use and
  nonuse of intranasal mupiricin
• Overall sternal SSI 2.7% untreated group
  v. 0.9% in the treatment group (p=0.005)
• Not a randomized control study
 Prevention of Nosocomial Infection in Cardiac
Surgery by Decontamination of the Nasopharynx
 and Oropharynx with Chlorhexidene Gluconate
               JAMA 2006; 296:2460
 • Prospectively, randomized, double-blind,
   placebo controlled trial in cardiac surgery
 • Oropharyngeal rinse and nasal ointment
   containing CHG or placebo
 • Patients were eligible whenever prolonged ICU
   stay (>5 days) or prolonged ventilation (> 2
   days) was expected after surgery
 • A significant reduction of 57.5% in S. aureus
   carriage compared with a reduction of 18.1% in
   placebo group (P<.001)
 • SSIs and pneumonias were significantly reduced
          Recent Literature
• Prophylactic intranasal mupirocin did not
  significantly reduce postoperative S.
  aureus infections (included all procedures)
 N Engl J Med 2002; 346:1871
Intranasal mupirocin starting day -1 to day
 +4 significantly decreased MRSA SSIs in
 orthopedic surgery J Hosp Infect 2003;
  SSI Infections in Orthopedic Surgery
       Clin Infect Dis 2002; 35:353

• Preoperative nasal carriage rate S. aureus was ~30%
• 614 patients were randomized to receive mupirocin vs.
• Eradication of nasal carriage was significantly more
  effective in the mupirocin group (83.5% vs. 27.8%)
• Mupirocin did not reduce SSIs due to S. aureus
  significantly (3.8% mupirocin group vs. 4.7% in placebo)
• In the mupirocin group, the rate of endogenous S.
  aureus infections was five times lower than in placebo
  group (ns)
• Study was not powered adequately for infections
                Recent Literature
                 Mupirocin cont.
Perioperative intranasal mupiricin
 decreased SSIs in nongeneral surgery
 (cardiothoracic and orthopedic) but not in
 general surgery Infect Control Hosp Epidemiol
 2005; 26:916
Intranasal mupiricin significantly reduced
 S. aureus SSI rates in cardiac surgery Am
 J Infect Control 2006; 34:44
Impact of Rapid Molecular Screening
    for MRSA in Surgical Wards
              British J Surg 2008; 95:381

• In 2006, nasal swabs were obtained before
  surgery for all patients undergoing elective and
  emergency procedures by PCR
• MRSA-positive patients were started on
  mupiricin nasal ointment and CHG body wash
• Overall 4.5% were MRSA-positive
• MRSA bacteremia fell by 38.5% (P<0.001)
• MRSA SSIs fell 12.7% ( P=0.031)
Ed’s Current Recommendations
• Use of systemic antimicrobial agents or
  mupiricin to eliminate MRSA carriage is not
  recommended for the general patient population
  or for pre-op decolonization for general surgery
• Pre-operative decolonization may be considered
  for MSSA and MRSA-colonized patients about to
  undergo selected high-risk surgical procedures,
  such as CV surgery, vascular procedures with
  placement of a graft, prosthetic joint
  implantation, and neurosurgical procedures with
  implantation of hardware.
       Ed’s Current Recommendations
• The optimal decolonization regiment is unclear,
  but mupiricin and CHG is reasonable.
• The use of vancomycin for surgical prophylaxis
  for certain high-risk procedures such as CV
  surgery, vascular procedures with placement of
  a graft, prosthetic joint implantation, and
  nuerosurgical procedures with implantation of
  hardware, for patients colonized with MRSA
  should be considered.
           No ESKAPE

E=Enterococcus faecium
S=Staphylococcus aureus
K=Klebsiella pneumoniae
A=Acinetobacter baumanni
P=Pseudomonas aeruginosa
E=Enterobacter species

            Rice; J Infect Dis 2008;April 15
             Ed’s Suggestions
• Adherence to evidenced-based prevention practices
  -Hand washing and contact precautions
  -CR-BSI bundle
  -VAP bundle
  -SSI bundle
  -CHG bathing in ICU
• Antimicrobial stewardship
• Decontamination of environment and equipment
• Second tier of interventions based on local
Burden of HAIs in the U.S., 2002

 • 1.7 million infections in hospitals
    – Most (1.3 million) were outside of ICUs
    – 4.5 per 100 admissions
 • 99,000 deaths associated with infection
    – 36,000 pneumonia;
    – 31,000 bloodstream infections

 Klevens, Edwards, Richards, et al. Pub Health Rep 2007;122:160-6
      Problem Enhanced by

•   Antimicrobial resistance
•   Emerging pathogens
•   Emergence of novel/virulent strains
•   Rapid worldwide spread
What It Takes to Win
  Engagement

  Education

  Execution

US Approach to Strategies in the
    Battle against HAI, 2006
     J Hosp Infect 2007; 65:3
• No single intervention prevents any HAI;
  rather a “bundle” approach, using a package
  of multiple interventions based on evidence
  provided by the infection control community
  and implemented by a multidisciplinary team
  is the model for successful HAI prevention
• Benchmarking is inadequate and a culture of
  zero tolerance is required
• A culture of accountability and
  administrative support is required
   New Belief →New Response
• Change focus from infection control to
  infection prevention
• Abandon 33% preventable target
 Am J Epidemiol 1985; 121:182
• Aim to eliminate all HAIs
• Requires culture change
 Essential Elements for Change
• Demand adherence to evidenced-based infection
  prevention practices
• Measurement and feedback of information
• Continuous learning and reflection
• Collaboration and teamwork between all levels of
  the organization (generate light not heat)
• Leadership support
• Everyone held accountable for compliance
• Empower all members of health care team
  (include patients and families) to ensure
Good ideas are not adopted
 They must be driven into
 practice with courageous
    Admiral Hyman Richover

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