Mupirocin effective in short-term MRSA decolonization

Topical antibiotic effective choice for reduction of nasal carriage, transmission during outbreaks.

Issue: December 2007

With recent reports of death or significant morbidity due to MRSA among the community adolescent population, MRSA is receiving widespread attention in the lay news and medical literature. MRSA has long been recognized as an important pathogen in the institutional setting, whereas community-associated MRSA’s role as an important pathogen is increasing. Decolonization may be an effective strategy in some patients to reduce risk for infection or transmission.

Edward A. Bell

Approximately 25% to 30% of the pediatric and adult population is colonized with S. aureus. Multiple body sites can be colonized, with the anterior nares the most densely colonized. Other colonized body sites include the skin, perineum, axilla, rectum and vagina. The throat can be colonized in infants and young children. Some children and adults may remain colonized for years. Those who are nasally colonized commonly have the organism on their hands, and thus they can be a source of transmission to others. Health care workers colonized with MRSA are a known source of transmission to pediatric and adult patients. Colonization of the nares or skin is a risk factor for infection following surgery or for patients receiving hemodialysis. Patients who have MRSA often fare worse than patients infected with methicillin-sensitive Staphylococcus aureus.

Researchers of a recently published study describe the significance of MRSA disease in the United States. Klevens and colleagues evaluated the incidence and distribution of invasive MRSA disease in nine U.S. communities in 2005. Observed cases of invasive MRSA (defined as isolation of MRSA from a normally sterile body site) numbered 8,987, equating to an incidence rate of 31.8 per 100,000. Those people aged 65 years and older had the highest incidence rate (127.7 per 100,000). Incidence rates for the pediatric population included (per 100,000): aged less than 1 year, 23.1; aged 1 year, 3.8; aged 2 to 4 years, 2.4; and aged 5 to 17 years, 1.4. The total incidence rate of invasive MRSA disease (31.8 per 100,000) is greater than the combined incidence rates of disease caused by pneumococcus, group A streptococcus, meningococcus and Haemophilus influenzae in 2005. Most cases were due to health care-associated MRSA (85%), 58.4% were community-onset and 26% were hospital-onset. CA-MRSA accounted for 13.7% of the total. The most commonly identified risk factors for community-onset and hospital-onset infection were history of hospitalization or surgery, long-term care residence and MRSA infection or colonization. Thus, while most cases of invasive MRSA occurred in patients with known risk factors, disease also occurred in those without established risk factors.

Measures to reduce transmission of MRSA and risk for infection are often difficult to implement.

Strategies to reduce MRSA transmission, infection

These strategies include frequent hand washing, proper cleaning of wounds and not sharing personal items (eg, towels or razors). Strategies to implement in health care settings have been published. Strategies to reduce the risk for infection and illness in the community setting are less clear and are not well-defined.

Decolonization of MRSA is one strategy that has been evaluated. Published studies of MRSA decolonization methods have evaluated its role in reducing MRSA colonization, preventing infection and controlling outbreaks. Most studies have evaluated the adult population, and relatively few have included children.

Several studies of methods to control infection and transmission of MRSA outbreaks in nurseries or neonatal intensive care units have been published.

Different agents have been studied to decolonize MRSA from individuals. The nares are the most frequently evaluated site for decolonization. Some studies have also attempted to decolonize other body sites. Topically-applied agents are most commonly evaluated, although some studies have additionally evaluated systemic antibiotics as a means to decolonize MRSA. Body washes or baths with topical antiseptics, such as chlorhexidine or bleach, have been recommend as treatment for decolonization of extranasal MRSA. These methods have not been well evaluated (ie, few published controlled trials), and benefit from their use is not clear. Although systemic antibiotics may offer advantages over topical antibiotic application to the nares alone, this must be balanced against the risk for systemic adverse effects and resistance.

Mupirocin (Bactroban Nasal ointment, GlaxoSmithKline) is the most frequently evaluated topical agent. It is labeled for use in patients aged 12 years and older and in health care workers to reduce infection risk and transmission during institutional outbreaks. Mupirocin is the topical antibiotic of choice for decolonization, as it is very effective for this use; decolonization of MRSA from the anterior nares can be expected in 90% to 100% of individuals.

Mupirocin has been shown to be more effective than topically-applied bacitracin and equally effective as some systemic regimens.

Differentiation of the term “decolonization” from “eradication” is important, as decolonization of MRSA is likely to be of short-term duration (with one-time use of mupirocin). Few studies have evaluated the ability of mupirocin to result in long-term (one year or longer) decolonization of MRSA. In evaluation of decolonization of health care workers, studies have shown that less than 50% remained free of MRSA nasal carriage at one year.

Resistance to mupirocin, although not common, has been reported in studies when used for decolonization or prevention of infection. A gene encoding for high-level mupirocin resistance has been identified. Although mupirocin can be highly effective in short-term elimination of nasal MRSA colonization, its use routinely is not recommended.

The CDC does not recommend routine use of mupirocin for decolonization. Mupirocin use should be limited to use in outbreaks or other high prevalence situations. Widespread use of mupirocin is offset by the necessity of surveillance cultures to identify candidates for decolonization, the likelihood of recolonization and the potential for resistance. Health care workers identified as a source of MRSA transmission should be treated with mupirocin. Health care workers colonized with MRSA, but who have not been linked epidemiologically to transmission, do not require treatment.

Although nasal mupirocin may effectively result in transient decolonization of MRSA, a reduction in risk for infection and illness is of paramount importance. Researchers of several studies (all in the adult population) have evaluated the effect of decolonization upon infection. Laupland and Conly recently reviewed the literature on the ability of mupirocin to prevent infection by decolonization of nasally-applied MRSA. Sixteen controlled trials were evaluated. Rates of infection overall in these studies were not reduced by mupirocin. However, some evidence for reduction in infection was demonstrated in select populations.

In surgical patients colonized with MRSA, mupirocin significantly reduced nosocomial infections due to S. aureus. Monthly application (five-day courses) of mupirocin in patients receiving continuous ambulatory peritoneal dialysis resulted in reduced catheter site infection due to S. aureus, although infection rates overall were not reduced (implying that other organisms may substitute as infecting pathogens).

A small study of adults with nasal MRSA colonization were given monthly mupirocin (five-day courses) in an attempt to reduce recurrent skin infections. Mupirocin was effective for this use, compared with placebo. The researchers of this literature review concluded that routine use of mupirocin to prevent infection is not supported by the current literature. Individuals more likely to benefit from mupirocin include those with high rates of nasal MRSA colonization who experience acute illness (eg, surgical patients or head trauma).

Conclusions

As MRSA is increasingly recognized as a cause of significant morbidity in health care settings and the community, the role of decolonization strategies are important to consider. Mupirocin, the most widely studied agent, can be effective at reducing nasal MRSA carriage and reducing transmission during epidemic situations. When used for decolonization of MRSA, the duration of decolonization has not been well evaluated, and some evidence indicates that recolonization rates are high.

The role of mupirocin to actually reduce infection from MRSA has not been clearly shown by controlled studies. Some evidence exists that specific subgroups of patients may benefit from mupirocin use. The role of mupirocin in the endemic pediatric population to prevent infection is less clear. Although the use of mupirocin may have a beneficial role in some patients and health care workers in controlling MRSA infection, the use of additional infection control practices are very important and cannot be understated.

For more information:

Edward A. Bell, PharmD, BCPS, is a Professor of Pharmacy Practice at Drake University College of Pharmacy and a Clinical Specialist at Blank Children’s Hospital, Des Moines, Iowa.

Klevens RM, Morrison MA, Nadle J, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007;298:1763-1771.

Bancroft EA. Antimicrobial resistance: It’s not just for hospitals. JAMA. 2007;298:1803-1804.

Laupland KB, Conly JM. Treatment of Staphylococcus aureus colonization and prophylaxis for infection with topical intranasal mupirocin: an evidence-based review. Clin Infect Dis. 2003;37:933-938.

Chen SF. Staphylococcus aureus decolonization. Pediatr Infect Dis J. 2005;24:79-80.

Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings 2007. www.cdc.gov/ncidod/dhqp/gl_isolation.html. Updated June 22, 2007. Accessed Nov. 20, 2007.

Management of multidrug-resistant organisms in healthare settings. www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf. Accessed Nov. 20, 2007.