Miller, Loren G. MD, MPH
Infectious disease physicians, nurses, hospital epidemiologists, clinical microbiologists, pharmacists, public health authorities, practicing physicians, and other health care professionals interested in the treatment of serious infections due to methicillin-resistant Staphylococcus aureus.
List 3 interventions that help to prevent the spread of methicillin-resistant Staphylococcus aureus colonization among inpatients and outpatients.
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Credit is based upon the approximate time it should take to read this publication and complete the assessment and evaluation. A minimum assessment score of 80% is required. Publication date is January 1, 2011. Requests for credit or contact hours must be postmarked no later than July 1, 2011, after which, this material is no longer certified for credit.
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Lauren Ero, MS, (managing editor), reports no relevant financial relationships.
Thomas M. File, Jr, MD, (reviewer), served as an advisor or consultant for Advanced Life Sciences, Astellas/Theravance, Cerexa/Forest, Ortho-McNeil, Protez, Merck, Nabriva, Pfizer, Schering Plough, Targanta, and Wyeth. He has received grants for clinical research from Cerexa, Ortho-McNeil, Protez, Pfizer, Boehringer Ingelheim, Gilead, and Tibotic.
Loren G. Miller, MD, MPH, (faculty), received a grant for clinical research from Cubist Pharmaceuticals, Inc, Pfizer Inc, and Merck. He served as an advisor or consultant for Pfizer, Inc, and Theravance, Inc.
Marguerite Jackson, PhD, RN, (reviewer), owns stock, stock options, or bonds from Cellestis, Inc.
Susan J. Rehm, MD, (senior editor), served as an advisor or consultant for Cubist Pharmaceuticals, Inc and Pfizer, Inc. She served as a speaker for Cubist Pharmaceuticals, Inc and Roche and received grants for clinical research from Cubist Pharmaceuticals, Inc.
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Methicillin-resistant Staphylococcus aureus (MRSA) infections have become a major pathogen in both the health care and community settings. By definition, a health care-associated MRSA infection occurs as a result of current or recent exposure to a hospital, rehabilitation facility or nursing home, dialysis center, an indwelling central venous catheter, or health care workers. Any other type of exposure is considered to be community-acquired or community-associated (CA) MRSA infection.1
Physicians frequently ask questions about how to control MRSA infections in the community and how to treat patients with recurrent infections. Controlling MRSA in both the inpatient and outpatient community settings through preventive measures is an important and extremely challenging task. Screening for colonization as a measure to control MRSA, for example, can be conducted in both community and health care settings. The overall objective of these types of programs is to prevent MRSA infections in hospitalized patients and MRSA and CA-MRSA infections in persons at risk in the outpatient setting via a variety of interventions. The purpose of this article is to provide an overview of evidence for the prevention of CA-MRSA and MRSA in hospitalized patients.
EVIDENCE-BASED METHODS TO PREVENT CA-MRSA
Recurrent CA-MRSA infections are an increasingly common problem seen in general practice. A significant number of patients who have a CA-MRSA infection (typically a skin infection) will have a recurrence. Data on recurrence rates of CA-MRSA infections are very limited and vary by study, likely depending on the population studied.2-4 In a prospective cohort of 201 patients discharged after hospitalization for a MRSA infection, 15% of CA-MRSA infected patients had a relapse after 4 months.2 The reinfection rate was 30% in a prospective study of 41 patients with skin and soft tissue infections related to CA-MRSA in outpatients infected with human immunodeficiency virus (HIV).3 The relapse rate of CA-MRSA skin and soft tissue infections in HIV-infected men who have sex with men was 31% in a retrospective medical chart review of 1203 outpatients from 3 outpatient practices in New York City.4
There are extremely limited data regarding prevention of CA-MRSA infection, and optimal methods are poorly understood. One way some experts recommend to prevent the spread of CA-MRSA is to decolonize patients at risk.5,6 However, the numbers of patients colonized with CA-MRSA during an acute infection varies from low to high, depending on the study population. Nasal colonization was not present during a CA-MRSA outbreak on a college football team in a retrospective study (n = 100).7 However, colonization of MRSA was present in 22% (76/350) of children admitted to the Driscoll Children's Hospital in Texas; in 37% (24/65) of patients with a CA-MRSA skin and soft tissue infection (inpatients hospitalized less than 72 hours and outpatients in an HIV clinic); and in 62% (38/61) of outpatients with MRSA skin and skin structure infections.8-10 Colonization of CA-MRSA in the general population is 1.5%.11
Interventions to eradicate colonization with the hopes of preventing MRSA have included the following: nasal antibiotics, systemic antibiotics, and body decolonization.5,6 These interventions have been poorly studied. Topical nasal antibiotics such as mupirocin, bacitracin, and retapamulin have been used to effectively eradicate colonization.12 Mupirocin is the best studied nasal topical antibiotic; however, its efficacy as monotherapy in preventing MRSA infections is not consistent and not established in many populations.13-15 One head-to-head study revealed that mupirocin was significantly more effective than bacitracin in eradicating S. aureus in healthy health care workers.15 Bacitracin was also inferior to rifampin in decolonizing S. aureus from the nares.16 A new antibiotic, retapamulin, which is indicated for impetigo in children, has the potential to be a good nasal MRSA decolonizer, but efficacy and safety data are lacking for this indication.17 Unfortunately, many studies show that MRSA eradication in the nose, although almost always highly efficacious at eradicating nasal colonization, may not always reduce the rate of MRSA infection.12,18 Furthermore, after treatment stops, colonization often returns.
The efficacy of systemic antibiotics such as rifampin and clindamycin in the eradication of S. aureus colonization has been evaluated. A meta-analysis determined that oral rifampin is an effective agent for the eradication of S. aureus colonization.19 However, development of resistance occurred in 0% to 40% of patients across 7 studies. Resistance to rifampin and toxicities of this drug limit its use in decolonization, and it probably should not be used without administration of another oral antibiotic active against MRSA or not used at all given the efficacy of other topical antibiotics. An older study of 22 patients with previous staphylococcal skin infections determined that oral clindamycin at 150 mg/d given for 3 months reduced the recurrence of skin infections (18%) compared with placebo (64%); however, no follow-up studies have confirmed results from this small trial.20
Emerging data suggest that CA-MRSA colonizes in other parts of the body, such as the axilla, groin, and the rectum. Chlorhexidine has been well studied and is considered an effective, well-tolerated decolonization agent.21 It has good activity against gram-positive organisms but less activity with gram-negative organisms and fungi. Similar to some other topical disinfectants, it has persistent antibiotic activity on the skin and has residual activity that attenuates recolonization.22
Chlorhexidine is best used after showering with soap and water.21 It is not recommended for mucous membranes and the ears because it can harm patients who have perforated tympanic membranes. Chlorhexidine with colored dyes can stain clothes, especially when used with chlorinated products.23 Rinsing with water afterwards is acceptable; however, natural soap and water will reduce the antimicrobial effect.24 The use of creams or lotions on the skin after the use of chlorhexidine will also lessen the antibiotic effect.25 Although the optimal duration of chlorhexidine use is unclear, the recommended period of use is 7 to 14 days.
Hexachlorophene (Phisohex) is another topical antiseptic, available only by prescription in the United States. It has good activity against S. aureus but has weak activity against gram-negative organisms and fungi. It is a more effective body decolonizer than soap and water. Its use is limited in young children and infants because it can be absorbed through the skin and can cause neurotoxicity. It can also be absorbed through the skin with repeated use, which may limit its use in health care workers.26
Bleach can be used as a body decolonizer at a concentration of 1 teaspoon per gallon of water (8 oz in half a bathtub or 25 gal of water); however, the safety and efficacy of the use of bleach, particularly in children, is unclear.27,28 Tea tree oils (Melaleuca alternifolia) have promise as an effective body decolonizer,29,30 but large studies are needed to better quantify its efficacy and safety. Povidone iodine may also be considered but is less effective than chlorhexidine in reducing skin colonization.21 Triclosan, which is a common additive to commercial soaps, is less effective than chlorhexidine; there is also no evidence that it prevents MRSA infection.31 Other less-studied interventions include octenidine dihydrochloride, which when used as a body wash combined with nasal mupirocin was effective in eradicating MRSA colonization in 32 hospitalized MRSA carriers.32
A small but significant proportion of patients carry MRSA in their pharynx but not other parts of the body. In a study of 2966 individuals, 13% of persons carried S. aureus only in their pharynx. Screening of throat swabs increased the sensitivity of detection by 26%.33 There are no recommendations regarding an optimal method on decolonizing the pharynx.
Household pets can also be reservoirs for MRSA.34,35 Case vignettes have described prevention of recurrent MRSA infections only after successful decolonization of the household cat or dog.
Available data suggest that environmental surfaces are probably easily colonized with MRSA.27,36,37 Methicillin-resistant Staphylococcus aureus can persist for days to weeks on surfaces, especially nonporous surfaces where transmission of MRSA to skin has been demonstrated several months after contamination in transmission models.37 A dilute concentration of bleach (1 tablespoon/quart of bleach) may be effective. Sprayable alcohol may also be used (eg, Lysol, Reckitt Benkiser North America, Parsippany, NJ; 79.6% alcohol, which is registered by the Environmental Protection Agency as an effective agent in eradicating MRSA on surfaces).38
Given the lack of data, the best choice for body decolonization is a combination of the nasal topical antibiotic, mupirocin, and chlorhexidine body washes. Some physicians also use systemic decolonization with rifampin or clindamycin.6 Patients who suffer from recurrent MRSA infections may benefit from these prevention methods as well as environmental decolonization including wiping of household surfaces with dilute bleach or alcohol spray, laundering clothes and linens in hot water, and decolonizing pets. However, other strategies are needed to effectively control the spread of MRSA in the community.
PREVENTING MRSA IN HOSPITALIZED PATIENTS
Colonization of MRSA is common in patients requiring hospitalization. Many additional patients acquire colonization during hospitalization or during a stay in a nursing home. There are now data suggesting that MRSA colonization is not only associated with an increased risk of MRSA infection,39-41 but also a higher risk of death.40,42 Besides MRSA colonization, risk factors that have been identified with an increased rate of MRSA infections include an intensive care setting, administration of 3 or more antibiotics, ulcers, surgical wounds, nasogastric or endotracheal tubes, drains, dialysis, and urinary or intravenous catheterization.39,43 Furthermore, patients who are at greatest risk for MRSA morbidity and mortality include those who have harbored MRSA for more than 1 year.42 Increased rates of infection have also been noted among MRSA colonized patients in community nursing homes compared with a hospital-based nursing home unit.40
Screening and decolonization have been interventions used to prevent MRSA infection in hospitalized patients. Mupirocin has been widely used for eradication of MRSA nasal carriage. Although mupirocin has been shown to be effective in eradicating MRSA colonization, many studies have shown that decolonization with mupirocin does not prevent infections in the hospital setting or in MRSA colonized patients undergoing major surgery.13,44 Studies that evaluated the benefits of universal screening and decolonization have shown conflicting results. One large quasi-experimental study determined that universal admission screening for MRSA carriage was associated with a large reduction of MRSA infections during admission and 30 days after discharge.45 In another large interventional cohort study, universal screening of MRSA did not reduce MRSA infections in patients undergoing major surgery.44 Many experts and medical organizations do not agree about the utility of routine MRSA screening and decolonization of those found to be MRSA colonized.46
Contact precautions, typically in a setting of a private isolation room, have been a means to prevent spread of MRSA in hospitals.47 However, there are also inherent isolation risks when using screening procedures and putting patients into contact isolation. Studies have shown that patients in isolation have predictable difficulties in the hospital.48-53 Patients in isolation are more likely to have preventable adverse events such as falls, pressure ulcers, and fluid/electrolyte disorders.48 They are less likely to have their vital signs checked, more likely to complain about their care, and less likely to be seen by physicians and nurses because of the requirement for practitioners to wear gowns and gloves.48,49,51,52 Patients who are in contact isolation are also more likely to be depressed, anxious, and angry.50,53 Future screening studies should evaluate the risks, as well as the benefits, of MRSA screening programs.
There are no proven effective strategies for the prevention of CA-MRSA at this time. Currently, the best preventive approach appears to be body decolonization using a combination of the nasal topical antibiotic, mupirocin, and chlorhexidine body washes.
Regarding health care-associated MRSA prevention strategies, nasal treatment alone of colonized patients in the hospital is not reliably successful at lowering MRSA infection rates. In addition, the risks and benefits of universal screening for colonized MRSA are not completely understood. Newer strategies and technologies need to be developed, implemented, and studied in order for decolonization to be an effective intervention. Although MRSA screening and decolonization may benefit some institutions or populations, further studies should be conducted before mandating MRSA screening programs.
1. Eguia JM, Chambers HF. Community-acquired methicillin-resistant Staphylococcus aureus
: epidemiology and potential virulence factors. Curr Infect Dis Rep
2. Miller LG, Quan C, Shay A, et al. A prospective investigation of outcomes after hospital discharge for endemic, community-acquired methicillin-resistant and -susceptible Staphylococcus aureus
skin infection. Clin Infect Dis
3. Skiest D, Brown K, Hester J, et al. Community-onset methicillin-resistant Staphylococcus aureus
in an urban HIV clinic. HIV Med
4. Shastry L, Rahimian J, Lascher S. Community-associated methicillin-resistant Staphylococcus aureus
skin and soft tissue infections in men who have sex with men in New York City. Arch Intern Med
5. Kaplan SL. Commentary: prevention of recurrent staphylococcal infections. Pediatr Infect Dis J
6. Miller LG, Tan J, Benitez E, et al. A prospective investigation of nasal mupirocin, hexachlorophene body wash, and systemic antibiotics for prevention of recurrent methicillin resistant Staphylococcus aureus
infections. Presentation 1002. 47th Annual Meeting of the Infectious Disease Society of America, Philadelphia PA, October 29th-November 1st, 2009.
7. Begier EM, Frenette K, Barrett NL, et al. A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus
among players on a college football team, facilitated by cosmetic body shaving and turf burns. Clin Infect Dis
8. Rahimian J, Khan R, LaScalea KA. Does nasal colonization or mupirocin treatment alter recurrence of methicillin-resistant Staphylococcus aureus
skin and skin structure infections? Infect Control Hosp Epidemiol
9. Alfaro C, Mascher-Denen M, Fergie J, et al. Prevalence of methicillin-resistant Staphylococcus aureus
nasal carriage in patients admitted to Driscoll Children's Hospital. Pediatr Infect Dis
10. Yang ES, Tan J, Eells S, et al. Body site colonization prevalence in patients with community-associated methicillin-resistant Staphylococcus aureus
and other forms of S. aureus
skin infections. Clin Microbiol Infect
11. Gorwitz RJ, Kruszon-Moran D, McAllister SK, et al. Changes in the prevalence of nasal colonization with Staphylococcus aureus
in the United States, 2001-2004. J Infect Dis
12. McConeghy KW, Mikolich DJ, LaPlante KL. Agents for the decolonization of methicillin-resistant Staphylococcus aureus
13. Laupland KB, Conly JM. Treatment of Staphylococcus aureus
colonization and prophylaxis for infection with topical intranasal mupirocin: an evidence-based review. Clin Infect Dis
14. Raz R, Miron D, Colodner R, et al. A one-year trial of nasal mupirocin in the prevention of recurrent staphylococcal nasal colonization and skin infection. Arch Intern Med
15. Soto NE, Vaghjimal A, Stah-Avicolli A, et al. Bacitracin versus mupirocin for Staphylococcus aureus
nasal colonization. Infect Control Hosp Epidemiol
16. McAnally TP, Lewis MR, Brown DR. Effect of rifampin and bacitracin on nasal carriers of Staphylococcus aureus
. Antimicrob Agents Chemother
17. Yang LP, Keam SJ. Spotlight on retapamulin in impetigo and other uncomplicated superficial skin infections. Am J Clin Dermatol
18. Tacconelli E, De Angelis G, de Waure C, et al. Rapid screening tests for methicillin-resistant Staphylococcus aureus
at hospital admission: systematic review and meta-analysis. Lancet Infect Dis
19. Falagas ME, Bliziotis IA, Fragoulis KN. Oral rifampin for eradication of Staphylococcus aureus
carriage from healthy and sick populations: a systemic review of the evidence from comparative trials. Am J Infect Control
20. Klempner MS, Styrt B. Prevention of recurrent staphylococcal skin infections with low-dose oral clindamycin therapy. JAMA
21. Boyce JM, Pittet D. Healthcare Infection Control Practices Advisory Committee, HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Guideline for hand hygiene in health-care settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand hygiene task force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm Rep
22. Mangram AJ, Horan TC, Pearson ML, et al. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control
24. Larson E. APIC guidelines for infection control practice: guideline for use of topical antimicrobial agents. Am J Infect Control
25. Frantz SW, Haines KA, Azar CG, et al. Chlorhexidine gluconate (CHG) activity against clinical isolates of vancomycin-resistant Enterococcus faecium
(VREF) and the effects of moisturizing agents on CHG residue accumulation on the skin. J of Hosp Infect
26. Trout ME. Hexachlorophene in perspective. J ClinPharmacol
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infections. Pediatr Infect Dis J
28. Gorwitz RJ, Jernigan DB, Powers JH, et al and Participants in the CDC-Convened Experts' Meeting on Management of MRSA in the Community. Strategies for clinical management of MRSA in the community: summary of an experts' meeting convened by the Centers for Disease Control and Prevention. 2006. Available at: http://www.cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdf
. Accessed December 8, 2010.
29. Caelli M, Porteous J, Carson CF, et al. Tea tree oil as an alternative topical decolonization agent for methicillin-resistant Staphylococcus aureus
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. Clin Infect Dis
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in a family and its pet cat. N Engl J Med
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(MRSA) in a pet dog associated with MRSA infection in household contacts. Clin Infect Dis
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37. Desai R, Pannaraj PS, Liu GY, et al. Survival and transmission of community-associated methicillin-resistant Staphylococcus aureus
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(MRSA) and Vancomycin Resistant Enterococcus faecalis
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(MRSA) amongst hospital patients initially only colonized with MRSA. J Hops Infect
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colonization in Veterans Affairs and community nursing homes. Am J Med
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colonization on patients in intensive care units of a Veterans Affairs Medical Center. Infect Control Hosp Epidemiol
44. Harbarth S, Fankhauser C, Schrenzel J, et al. Universal screening for methicillin-resistant Staphylococcus aureus
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in three affiliated hospitals. Ann Intern Med
46. Peterson LR, Diekema DJ. To screen or not to screen for methicillin-resistant Staphylococcus aureus
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48. Stelfox HT, Bates DW, Redelmeier DA. Safety of patents isolated for infection control. JAMA
49. Evans HL, Shaffer MM, Hughes MG, et al. Contact isolation in surgical patents: a barrier to care? Surgery
50. Tarzi S, Kennedy P, Stone S, et al. Methicillin-resistant Staphylococcus aureus
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51. Kirkland KB, Weinstein JM. Adverse effects of contact isolation. Lancet
52. Saint S, Higgins LA, Nallamothu BK, et al. Do physicians examine patients in contact isolation less frequently? A brief report. Am J Infect Control
53. Catalano G, Houston SH, Catalano MC, et al. Anxiety and depression in hospitalized patents in resistant organism isolation. South Med J
A minimum assessment score of 80% is required.
Colonization of CA-MRSA in the general population is:
Interventions to eradicate colonization of MRSA have included the following:
All of the above
A. and C. only
The best choice for decolonization of MRSA is a combination of:
Bleach and clindamycin
Mupirocin and rifampin
Mupirocin and chlorhexidine body washes
Triclosan and alcohol-based rubs
None of the above
The following statements regarding prevention of MRSA in hospitalized patients are true:
Decolonization of MRSA with mupirocin prevents infections in the hospital setting.
Universal screening of MRSA reduces infections in hospitalized patients.
MRSA colonization is not only associated with an increased risk of MRSA infection, but also a higher risk of death.
All of the above
B. and C. only
Hospitalized patients in isolation owing to MRSA infections may be at risk for:
Anxiety and depression
Infrequent contact with nurses and physicians
All of the above
A. and C. only
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