Colonization and Colonization and Decolonization of MRSADecolonization of MRSA

Ed Septimus, MD, FIDSA, SHEA, FACP

eseptimus@gmail.com

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; 15:78Am J Kidney Dis 1986; 2:281

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; 10:505Perit 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 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

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

Contaminated Surfacesand Shared Items

Frequent Contact

Cleanliness

Crowding

Compromised Skin

Factors that Facilitate TransmissionFactors that Facilitate Transmission

Antimicrobial Use

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

Clin Infect Dis 2008; 46:752

Epidemiology MSSA and MRSAEpidemiology MSSA and MRSA

Reservoirs

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 Epidemiology continuedcontinued

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 Epidemiology continuedcontinued

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 inRole of Nasal Carriage inS. aureus S. aureus InfectionsInfectionsLancet Infect Dis 2005; 5:751

13-25%

40%

30-39%

Frequency of MRSA ColonizationFrequency of MRSA Colonization at Various Body Sitesat Various Body Sites

Hill RLR et al. J Antimicrob Chemother 1988;22:377Sanford MD et al. Clin Infect Dis 1994;19:1123

Evaluation of a Strategy of Screening Evaluation of a Strategy of Screening Multiple Anatomic Sites for MRSA at Multiple Anatomic Sites for MRSA at

Admission to a Teaching HospitalAdmission 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

S. Aureus S. Aureus Intestinal Colonization Associated Intestinal Colonization Associated with Increased Frequency of with Increased Frequency of S. aureus S. aureus on Skin on Skin

in Hospitalized Patientsin Hospitalized PatientsBMC Infect Dis 2007; 7:105

Epidemiology of Epidemiology of S. aureus S. aureus Colonization in Colonization in Nursing Home ResidentsNursing 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

Epidemiology of Epidemiology of S. aureus S. aureus Colonization in Nursing Colonization in Nursing Home ResidentsHome Residents

Clin Infect Dis 2008;46: May 1

Throat Swabs Are Necessary to Reliably Throat Swabs Are Necessary to Reliably Detect Carriers of Detect Carriers of S. aureusS. 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 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

DecolonizationDecolonization

Eradication of MRSA Colonization

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

What sites of MRSA colonization should What sites of MRSA colonization should be targeted and does it work?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;4J 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; 41:127J Infect Dis 1999; 180:896

NonsurgicalNonsurgical

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)

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 PatientsICHE 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

CommentsComments• 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 useClin Infect Dis 2007; 45:541

• Mupiricin resistance noted in 24% of isolates and an additional 5% after treatmentClin 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

SurgicalSurgical

• 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

S. aureus carriage and risk of surgical site infections

Guidelines for Prevention of Surgical Site infections (SSI),

1999Infect Control Hosp Epidemiol 1999; 20:247

Mupirocin

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

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 0.25-0.92)

-84.6% PFGE match between nares and SSI

• All surgical procedures combined-overall infection rate low

Antibiotic Prophylaxis in Cardiac Antibiotic Prophylaxis in Cardiac Surgery, Part IISurgery, Part II

Society of Thoracic Surgeons (STS)www.sts.org 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 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

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

Recent LiteratureMupirocin

• 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

SSI Infections in Orthopedic SurgeryClin 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

Recent LiteratureMupirocin 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 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.

Ed’s Current Recommendationscontinued

• 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.

http://hcupnet.ahrq.gov

Rice; J Infect Dis 2008;April 15

No ESKAPENo ESKAPE

E=Enterococcus faecium

S=Staphylococcus aureus

K=Klebsiella pneumoniae

A=Acinetobacter baumanni

P=Pseudomonas aeruginosa

E=Enterobacter species

Ed’s SuggestionsMDRO

• 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

Burden of HAIs in the U.S., 2002Burden 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 byProblem Enhanced by

• Antimicrobial resistance

• Emerging pathogens

• Emergence of novel/virulent strains

• Rapid worldwide spread

What It Takes to WinWhat It Takes to Win

Engagement

Education

Execution

Evaluation

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

Good ideas are not adopted Good ideas are not adopted automatically.automatically.

They must be driven into They must be driven into practice with courageous practice with courageous

patience.patience.Admiral Hyman Richover