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Colonization and Decolonization of MRSA

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1 Colonization and Decolonization of MRSA
Ed Septimus, MD, FIDSA, SHEA, FACP



4 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

5 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 if a carrier ICHE 1994; 15:78 Am J Kidney Dis 1986; 2:281

6 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 Clin Microbiol Rev 1997; 10:505 Perit Dial Int 1996; 16:352

7 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

8 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 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

9 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) -cleanliness -compromised skin integrity -contaminated objects and environment -crowded living

10 Factors that Facilitate Transmission
Defense Offense Frequent Contact Crowding Antimicrobial Use Compromised Skin Contaminated Surfaces and Shared Items Cleanliness

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

12 Epidemiology MSSA and MRSA
Reservoirs Humans are the natural reservoirs for S. aureus % 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.

13 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

14 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

15 Role of Nasal Carriage in S
Role of Nasal Carriage in S. aureus Infections Lancet Infect Dis 2005; 5:751

16 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

17 Evaluation of a Strategy of Screening Multiple Anatomic Sites for MRSA at Admission to a Teaching Hospital Infect Control Hosp Epidemiol 2006; 27: Site % Positive Nares Rectum Axilla Nares+Axilla Nares+Rectum

18 S. Aureus Intestinal Colonization Associated with Increased Frequency of S. aureus on Skin in Hospitalized Patients BMC Infect Dis 2007; 7:105

19 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

20 Epidemiology of S. aureus Colonization in Nursing Home Residents Clin Infect Dis 2008;46: May 1

21 Throat Swabs Are Necessary to Reliably Detect Carriers of S
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 ( ) 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

22 Decolonization

23 Eradication of MRSA Colonization
Systemic antimicrobials Topical intranasal mupiricin Bathing with CHG Combination therapy What sites of MRSA colonization should be targeted and does it work?

24 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

25 Nonsurgical

26 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 (P=NS)

27 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

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

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

30 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

31 Comments 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 Risk of development of drug resistance especially with rifampin Antimicrob Agents Chemother 1993; 37:1334

32 Surgical

33 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 populations Colbeck JC et al. Can Serv Med J 1959; 15: Weinstein HJ. New Engl J Med 1959; 260: Williams REO et al. Br Med J 1959; 2:

34 Guidelines for Prevention of Surgical Site infections (SSI), 1999 Infect Control Hosp Epidemiol 1999; 20:247 Mupirocin No recommendation to preoperatively apply mupirocin to nares to prevent SSI-unresolved issue

35 Randomized Trial of Prophylactic Mupiricin + CHG Shower 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 ) -84.6% PFGE match between nares and SSI All surgical procedures combined-overall infection rate low

36 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)

37 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

38 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

39 Recent Literature 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

40 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. 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

41 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

42 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)


44 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 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.

45 Ed’s Current Recommendations continued
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.


47 Rice; J Infect Dis 2008;April 15
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

48 Ed’s Suggestions MDRO 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

49 Klevens, Edwards, Richards, et al. Pub Health Rep 2007;122:160-6
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 To summarize results of CDC’s findings, about 1.7 million healthcare-associated infections occurred in U.S. hospitals. Of these, most (1.3 million) were outside of intensive care units. These numbers can also be presented as 9.3 infections per 1,000 patient-days, or 4.5 per 100 admissions. There were an estimated 99,000 deaths associated with these infections. The body sites associated with the greatest number of deaths were the estimated 36,000 deaths from pneumonia, and 31,000 from bloodstream infections. In the United States, HAIs add an estimated $ billion to the cost of patient care (2001 dollars).[5] Klevens, Edwards, Richards, et al. Pub Health Rep 2007;122:160-6

50 Problem Enhanced by Antimicrobial resistance Emerging pathogens
Emergence of novel/virulent strains Rapid worldwide spread

51 What It Takes to Win Engagement Education Execution Evaluation

52 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

53 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

54 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 compliance


56 Admiral Hyman Richover
Good ideas are not adopted automatically. They must be driven into practice with courageous patience. Admiral Hyman Richover

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