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Colonization and Decolonization of MRSA Ed Septimus, MD, FIDSA, SHEA, FACP [email protected] 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

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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


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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


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Carriage of S. aureus as a Risk Factor for Infection

  • CAPD

    -S. aureus leading cause of CAPD related infections

    -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


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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


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Carriage of S. aureus as a Risk Factor for Infection

  • Intravascular Device-Associated bacteremia

    -Patients with an IV device who are colonized with S. aureus have a higher rateof 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


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Colonization, Fomites, and Virulence:Rethinking the Pathogenesis of CA-MRSA InfectionClin 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)

    -cleanliness

    -compromised skin integrity

    -contaminated objects and environment

    -crowded living


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Frequent Contact

Crowding

Defense

Offense

Cleanliness

Antimicrobial

Use

Contaminated Surfaces

and Shared Items

Compromised Skin

Factors that Facilitate Transmission


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Colonization, Fomites, and Virulence:Rethinking the Pathogenesis of CA-MRSA InfectionClin Infect Dis 2008; 46:752


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Epidemiology MSSA and MRSA

Reservoirs

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.

Colonized and infected patients are the major reservoir of MRSA.


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Epidemiology continued

3. Nasal colonization with MRSA is the single most important determinant of subsequent MRSA infections

  • Patterns of carriage:

    persistent 20% (12-30%)

    intermittent 30% (16-70%)

    non-carriage 50% (16-69)

    J Clin Microbiol 1999;37:3133


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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


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Role of Nasal Carriage inS. aureus InfectionsLancet Infect Dis 2005; 5:751


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Frequency of MRSA Colonization

at Various Body Sites

13-25%

40%

30-39%

Hill RLR et al. J Antimicrob Chemother 1988;22:377

Sanford MD et al. Clin Infect Dis 1994;19:1123


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Evaluation of a Strategy of Screening Multiple Anatomic Sites for MRSA at Admission to a Teaching HospitalInfect Control Hosp Epidemiol 2006; 27:181-184

Site% Positive

Nares 73

Rectum 47

Axilla 25

Nares+Axilla 83

Nares+Rectum 91


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S. Aureus Sites for MRSA at Admission to a Teaching HospitalIntestinal Colonization Associated with Increased Frequency of S. aureus on Skin in Hospitalized PatientsBMC Infect Dis 2007; 7:105


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Epidemiology of Sites for MRSA at Admission to a Teaching HospitalS. aureus Colonization in Nursing Home ResidentsClin 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


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Epidemiology of Sites for MRSA at Admission to a Teaching HospitalS. aureus Colonization in Nursing Home ResidentsClin Infect Dis 2008;46: May 1


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Throat Swabs Are Necessary to Reliably Detect Carriers of Sites for MRSA at Admission to a Teaching HospitalS. aureusClin 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 inoculated

  • 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


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Decolonization Sites for MRSA at Admission to a Teaching Hospital


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Eradication of MRSA Colonization Sites for MRSA at Admission to a Teaching Hospital

  • Systemic antimicrobials

  • Topical intranasal mupiricin

  • Bathing with CHG

  • Combination therapy

    What sites of MRSA colonization should be targeted and does it work?


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General Comments Sites for MRSA at Admission to a Teaching Hospital

  • 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


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Nonsurgical Sites for MRSA at Admission to a Teaching Hospital


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Impact of Universal IP Surveillance and Decolonization on Rates of HA-MRSA BSI2006 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 (P=NS)


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Reduction in Incidence of Nosocomial MRSA Infection in an ICU:Role of Treatment with Mupiricin Ointment and CHG Baths for Nasal Carriers ofMRSAICHE 2006; 27:185


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Select Use of Intranasal Mupiricin and CHG Bathing and the Incidence of MRSA Colonization and Infection Among ICU PatientsICHE 2007;28:1155


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Effectiveness of CHG Bathing to Reduce Catheter-Associated Bloodstream Infections in MICUArch Intern Med 2007; 167:2073


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Randomized Controlled Trial of CHG for Washing, Intranasal Mupiricin, and Rifampin and Doxycycline Versus No Treatment for the Eradication of MRSA ColonizationClin Infect Dis 2007; 44:178


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Comments Mupiricin, and Rifampin and Doxycycline Versus No Treatment for the Eradication of MRSA Colonization

  • Increased mupiricin use has been associated with increased drug resistance and failure to clear S. aureus

    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


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Surgical Mupiricin, and Rifampin and Doxycycline Versus No Treatment for the Eradication of MRSA Colonization


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S. aureus Mupiricin, and Rifampin and Doxycycline Versus No Treatment for the Eradication of MRSA Colonization 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 populations

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


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Guidelines for Prevention of Surgical Site infections (SSI), 1999Infect Control Hosp Epidemiol 1999; 20:247Mupirocin

No recommendation to preoperatively apply mupirocin to nares to prevent SSI-unresolved issue


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Randomized Trial of Prophylactic Mupiricin + CHG Shower 1999N 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 0.25-0.92)

    -84.6% PFGE match between nares and SSI

    • All surgical procedures combined-overall infection rate low


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Antibiotic Prophylaxis in Cardiac Surgery, Part II 1999Society of Thoracic Surgeons (STS)www.sts.orgFebruary 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)


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Intranasal Mupiricin Reduces Sternal Wound Infect after Open Heart Surgery in Diabetics and NondiabeticsAnn 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


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Prevention of Nosocomial Infection in Cardiac Surgery by Decontamination of the Nasopharynx and Oropharynx with Chlorhexidene Gluconate (CHG)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


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Recent Literature Decontamination of the Nasopharynx and Oropharynx with Chlorhexidene Gluconate (CHG)Mupirocin

  • 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; 54:196


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SSI Infections in Orthopedic Surgery Decontamination of the Nasopharynx and Oropharynx with Chlorhexidene Gluconate (CHG)Clin Infect Dis 2002; 35:353

  • Preoperative nasal carriage rate S. aureus was ~30%

  • 614 patients were randomized to receive mupirocin vs. placebo

  • 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


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Recent Literature Decontamination of the Nasopharynx and Oropharynx with Chlorhexidene Gluconate (CHG)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


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Impact of Rapid Molecular Screening for MRSA in Surgical WardsBritish 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)


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Ed’s Current Recommendations Wards

  • 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 patients.

  • 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.


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Ed’s Current Recommendations Wardscontinued

  • 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.



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No ESKAPE Wards

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


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Ed’s Suggestions WardsMDRO

  • 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 epidemiology


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Burden of HAIs in the U.S., 2002 Wards

  • 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


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Problem Enhanced by Wards

  • Antimicrobial resistance

  • Emerging pathogens

  • Emergence of novel/virulent strains

  • Rapid worldwide spread


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What It Takes to Win Wards

  • Engagement

  • Education

  • Execution

  • Evaluation


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US Approach to Strategies in the Battle against HAI, 2006 WardsJ 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


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New Belief Wards→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


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Essential Elements for Change Wards

  • 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 compliance


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Good ideas are not adopted automatically. WardsThey must be driven into practice with courageous patience.

Admiral Hyman Richover


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