An article from Infectious Diseases in Children: Pharmacology Consult

http://www.idinchildren.com

*Many factors involved in decolonization of _S. aureus_*

*Current treatment strategies demonstrate varying levels of effectiveness.*

_by Edward A. Bell, PharmD, BCPS_
_Special to Infectious Diseases in Children_

March 2007

The February _Pharmacology Consult_ column discussed the selection and use of antibiotic therapy for community-acquired methicillin-resistant _Staphylococcus aureus_ infection and briefly mentioned the use of mupirocin for decolonization of nasal methicillin-resistant _Staphylococcus aureus_. This month’s _Pharmacology Consult_ will expand upon the use of decolonization measures of methicillin-resistant _Staphylococcus aureus_.

_Staphylococcus aureus_ is a major cause of infection in children and adults. This bacterial organism colonizes the skin and mucous membranes in up to 50% of children. While the anterior nares are the most densely colonized site, _S. aureus_ can also colonize the throat, perineum and rectum. Nasal carriage of _S. aureus_ is a known risk factor for subsequent infection.

Studies have attempted to reduce _S. aureus_ colonization in hopes of reducing infection. A variety of agents, both topical and systemic, have been used to decolonize _S. aureus_, although mupirocin (Bactroban Nasal, GlaxoSmithKline) has been most commonly used. Mupirocin nasal ointment is FDA labeled for the eradication of nasal colonization of MRSA in adults (>12 years of age) as part of a comprehensive infection control program during institutional outbreaks of infections with _S. aureus_. It is not FDA labeled for use in children 11 years of age and younger.

*Decolonization studies*

Controlled studies of decolonization have primarily been conducted in the adult population.

A large controlled trial of adult surgical patients found that intranasal mupirocin significantly reduced surgical infection in patients who were nasal carriers of _S. aureus_. Nasally applied mupirocin has also been shown to significantly reduce _S. aureus_ infection in adult dialysis patients.

Several studies have evaluated the ability of mupirocin to eradicate nasal _S. aureus_ carriage in health care workers. Nasally applied mupirocin significantly reduced _S. aureus_ nasal colonization, and although re-colonization occurred in many patients, at one year of follow-up, fewer patients who had received mupirocin harbored nasal _S. aureus_ as compared with controls. In an uncontrolled study in an ICU setting, nasally applied mupirocin and chlorhexidine baths given to all patients growing nasal MRSA reduced rates of nosocomial MRSA infection during the five years of observation.

Not all studies evaluating mupirocin have been positive. In a randomized, double blind trial, mupirocin and chlorhexidine body washing were compared with placebo in 102 hospitalized adult patients colonized with MRSA. Other body sites (groin, skin, urine), in addition to the nose, were cultured for the presence of MRSA. The primary study objective was the rate of eradication of overall MRSA colonization. There was no difference in the rate of overall MRSA eradication of the treatment group (25%) compared with placebo (18%). The eradication rate of nasal MRSA in the treatment group was low in this study, only 44%. The researchers speculate that additional infection control practices may be necessary to control MRSA colonization. In a large (n=1,602) randomized, double blind, placebo-controlled trial, nasal mupirocin prophylaxis was evaluated in preventing nosocomial _S. aureus_ infection in nonsurgical patients. No difference was found in infection rates between the treatment and placebo groups in this study.

In another study, decolonization treatment was compared with no treatment in an attempt to eradicate MRSA from multiple body sites (nares, perineum, skin, medical device exit site). In an open-label, randomized manner, hospitalized adults growing MRSA from at least one body site received either nasally applied mupirocin plus chlorhexidine body washes plus rifampin and doxycyline (all for seven days) or no treatment. The primary outcome was MRSA eradication from all body sites at three months of follow-up. Note that this study included two systemic treatments, in addition to mupirocin, and included a longer time of follow-up. At three months of follow-up, 74% of treatment patients remained negative for MRSA growth, compared with 32% of patients receiving no treatment (P<0.05). Patients who remained colonized at three months were more likely to grow a mupirocin-resistant isolate.

Professional medical societies and organizations recommend that mupirocin and other decolonization therapies be considered as part of an infection control treatment strategy. In a consensus statement published by the Chicago-area Neonatal MRSA Working Group, recommendations for the prevention and control of MRSA colonization and infection in the neonatal ICU setting included the use of mupirocin for decolonization of neonates and health care workers as part of a comprehensive strategy, if deemed necessary. The 2006 _Red Book_ states that mupirocin can be considered in select patients (chronic carriers, those predisposed to infection with _S. aureus_) or health care workers in an attempt at eradication. However, mupirocin should not be used routinely or in all patients, as resistance has occurred.

*Conclusion*

Pharmacologic decolonization treatment strategies have demonstrated success in some studies of patients colonized with MRSA. Not all studies, however, have demonstrated effectiveness in reducing rate of infection.

Most studies have evaluated mupirocin and other agents for this use in adult hospitalized patients, and mupirocin is FDA labeled for use only in those aged 12 years and older. Most studies have evaluated twice daily dosing for a five-day duration, and mupirocin is FDA labeled for this dose (using 0.5 gm applied to each nostril, or one-half of a 1 gm single-dose tube). Resistance to mupirocin has occurred in studies, and a high-level mupirocin resistant gene has been identified in community-acquired MRSA strains.

When attempting to decolonize MRSA and reduce the risk of infection from this organism in a specific patient or group of patients, several important factors remain unknown, such as whether the most effective treatment regimen is the use of topical agents, such as mupirocin, or topical agents plus systemic antibiotics. The use of systemic agents, such as rifampin, present additional considerations (eg, drug-drug interactions, resistance, systemic adverse effects). While the anterior nares remain an important site of MRSA colonization, other body sites can still harbor MRSA.

The duration of decolonization from treatment has not been well studied or delineated. The use of mupirocin for decolonization and infection rate reduction in ambulatory patients has not been studied, thus pharmacologic decolonization treatment strategies should not be routinely used. Mupirocin may benefit some colonized children who suffer from numerous infections or who are at increased risk of severe infection. The use of additional infection control practices, such as frequent hand washing, should continue to be emphasized.

*For more information:*
· Edward A Bell, PharmD, BCPS, is a Professor of Pharmacy Practice at Drake University College Pharmacy and a Clinical Specialist at Blank Children’s Hospital, Des Moines, Iowa.
· Chen SF. _Staphylococcus aureus_ decolonization. _Pediatr Infect Dis J_. 2005;24:79-80
· Perl TM, Cullen JJ, Wenzel RP, et al. Intranasal mupirocin to prevent postoperative _Staphylococcus aureus_ infections. _N Engl J Med_. 2002;346:1871-1877
· Sandri AM. Reduction in incidence of nosocomial methicillin-resistant _Staphylococcus aureus_ (MRSA) infection in an intensive care unit: role of treatment with mupirocin ointment with chlorhexidine baths for nasal carriers of MRSA. _Infect Control Hosp Epidemiol_. 2006;27:185-187.
· Harbarth S, Dharan S, Liassine N, et al. Randomized placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant _Staphylococcus aureus. Antimicrob Agents Chemother_. 1999;43:1412-1416.
· Simor AE, Phillips E, McGreer A, et al. Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for eradication of methicillin-resistant _Staphylococcus aureus_ colonization. _Clin Infect Dis_. 2007;44:178-185.
· Muto CA, Jernigan JA, Ostrowske, BE, et al. SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of _Staphylococcus aureus_ and Enterococcus. _Infec Control Hosp Epidemiol_. 2003;24:362-386.
· Wertheim HF, Vos MC, Ott A, et al. Mupirocin prophylaxis against nosocomial _Staphylococcus aureus_ infections in nonsurgical patients. _Ann Intern Med_. 2004;140:419-425.
· Gerber SI. Management of outbreaks of methicillin-resistant _Staphylococcus aureus_ infection in the neonatal intensive care unit: a consensus statement. _Infec Control Hosp Epidemiol_. 2006;27:139-145.