Colonization and Decolonization of MRSA

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Colonization and Decolonization of MRSA

• Ed Septimus, MD, FIDSA, SHEA, FACP
• eseptimus_at_gmail.com

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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 10505
• -Orthopedics ICHE 2000 21319
• -Cardiac J Infect Dis 1995 171216

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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 1578
• Am J Kidney Dis 1986 2281

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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 10505
• Perit Dial Int 1996 16352

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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 130221
• -Higher carriage rate of S. aureus with
  progressive HIV (asymptomatic 23.5 AIDS 50)
  Eur J Clin Microbiol Infect Dis 1992 11985

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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 rate of S. aureus
  bacteremia RR 12.4 Am J Med 1996 100509
• -Nasal carriage of S. aureus was identified by
  molecular studies to be the source of line
  related bacteremia N Engl J Med 2001 34411

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Colonization, Fomites, and VirulenceRethinking
the Pathogenesis of CA-MRSA InfectionClin Infect
Dis 2008 46752

• 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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Factors that Facilitate Transmission
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Colonization, Fomites, and VirulenceRethinking
the Pathogenesis of CA-MRSA InfectionClin Infect
Dis 2008 46752
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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 1999373133

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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 161667
• J Clin Microbiol 1999 373133
• 6.Nasal carriers who are also perineal carriers
  have higher S. aureus loads and disperse more S.
  aureus ICHE 2002 23495

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Role of Nasal Carriage inS. aureus
InfectionsLancet Infect Dis 2005 5751
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Frequency of MRSA Colonization at Various
Body Sites
13-25 40 30-39
Hill RLR et al. J Antimicrob Chemother
198822377 Sanford MD et al. Clin Infect Dis
1994191123
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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 27181-184

• Site Positive
• Nares 73
• Rectum 47
• Axilla 25
• NaresAxilla 83
• NaresRectum 91

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S. Aureus Intestinal Colonization Associated with
Increased Frequency of S. aureus on Skin in
Hospitalized PatientsBMC Infect Dis 2007 7105
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Epidemiology of S. aureus Colonization in Nursing
Home ResidentsClin Infect Dis 200846 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 S. aureus Colonization in Nursing
Home ResidentsClin Infect Dis 200846 May 1
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Throat Swabs Are Necessary to Reliably Detect
Carriers of S. aureusClin Infect Dis 2007 45475

• 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
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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?

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General Comments

• Short-term eradication generally successful, but
  most patients become recolonized later with same
  strain Arch Intern Med 1994 1541505
• Most regiments seem to last up to 90 days
  therefore decolonization rather than eradication
  is a better term Clin Infect Dis 2007 44186
• Recolonization rates at 1 year approach 50 for
  healthy HCW and 75 for patients on PD
• Cochrane Database Syst Rev 20034
• J Kidney Dis 1993 22708
• Recolonization rate at 4 months in patients on HD
  was 56 and recolonization rate was 71 in
  HIV-positive patients ASAIO J 1995 41127
• J Infect Dis 1999 180896

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Nonsurgical
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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 (P0.02)
• 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 (PNS)

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Reduction in Incidence of Nosocomial MRSA
Infection in an ICURole of Treatment with
Mupiricin Ointment and CHG Baths for Nasal
Carriers of MRSAICHE 2006 27185
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Select Use of Intranasal Mupiricin and CHG
Bathing and the Incidence of MRSA Colonization
and Infection Among ICU PatientsICHE 2007281155
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Effectiveness of CHG Bathing to Reduce
Catheter-Associated Bloodstream Infections in
MICUArch Intern Med 2007 1672073
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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 44178
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Comments

• Increased mupiricin use has been associated with
  increased drug resistance and failure to clear S.
  aureus
• Diagn Microbiol Infect Dis 2002 42283
• ASC in SICU for MRSA were tested for mupiricin
  resistance-13.2 were resistant despite low-level
  in-hospital use
• Clin Infect Dis 2007 45541
• Mupiricin resistance noted in 24 of isolates and
  an additional 5 after treatment
• Clin Infect Dis 2007 44178
• Frequent adverse effects of systemic
  antimicrobial therapy with 25 of patients
  developing GI side effects and 5 discontinuing
  therapy
• Clin Infect Dis 2007 44178
• Risk of development of drug resistance especially
  with rifampin Antimicrob Agents Chemother 1993
  371334

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Surgical
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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
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 20247Mupirocin

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

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Randomized Trial of Prophylactic Mupiricin CHG
ShowerN Engl J Med 20023461871

• Nasal carriage of S. aureus eliminated in 83.4
  v. 27.4 in placebo (plt0.001)
• 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
IISociety 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)

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Intranasal Mupiricin Reduces Sternal Wound Infect
after Open Heart Surgery in Diabetics and
NondiabeticsAnn Thorac Surg 2001 711572

• 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 (p0.005)
• 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 2962460

• 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 (gt5 days) or prolonged ventilation (gt 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 (Plt.001)
• SSIs and pneumonias were significantly reduced

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Recent LiteratureMupirocin

• Prophylactic intranasal mupirocin did not
  significantly reduce postoperative S. aureus
  infections (included all procedures) N Engl J Med
  2002 3461871
• Intranasal mupirocin starting day -1 to day 4
  significantly decreased MRSA SSIs in orthopedic
  surgery J Hosp Infect 2003 54196

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SSI Infections in Orthopedic SurgeryClin Infect
Dis 2002 35353

• 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 LiteratureMupirocin cont.

• Perioperative intranasal mupiricin decreased SSIs
  in nongeneral surgery (cardiothoracic and
  orthopedic) but not in general surgery Infect
  Control Hosp Epidemiol 2005 26916
• Intranasal mupiricin significantly reduced S.
  aureus SSI rates in cardiac surgery Am J Infect
  Control 2006 3444

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Impact of Rapid Molecular Screening for MRSA in
Surgical WardsBritish J Surg 2008 95381

• 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 (Plt0.001)
• MRSA SSIs fell 12.7 ( P0.031)

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Eds 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.

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Eds 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.

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No ESKAPE

• EEnterococcus faecium
• SStaphylococcus aureus
• KKlebsiella pneumoniae
• AAcinetobacter baumanni
• PPseudomonas aeruginosa
• EEnterobacter species

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Eds 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

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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
2007122160-6
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Problem Enhanced by

• Antimicrobial resistance
• Emerging pathogens
• Emergence of novel/virulent strains
• Rapid worldwide spread

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What It Takes to Win

• Engagement
• Education
• Execution
• Evaluation

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US Approach to Strategies in the Battle against
HAI, 2006J Hosp Infect 2007 653

• 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 ?New Response

• Change focus from infection control to infection
  prevention
• Abandon 33 preventable target
• Am J Epidemiol 1985 121182
• Aim to eliminate all HAIs
• Requires culture change

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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

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

• Admiral Hyman Richover