Mupirocin-Based Decolonization of Staphylococcus aureus Carriers in Residents of 2 Long-Term Care Facilities: A Randomized, Double-Blind, Placebo-Controlled Trial

Lona Mody () 0 Carol A. Kauffman 0 1 Shelly A. McNeil 0 1 Andrzej T. Galecki 2 Suzanne F. Bradley 0 1 0 University of Michigan Medical School 1 Infectious Diseases, Department of Internal Medicine, Veterans Affairs Ann Arbor Healthcare System 2 Institute of Gerontology, University of Michigan Ann Arbor , Michigan Mupirocin has been used in nursing homes to prevent the spread of methicillin-resistant Staphylococcus aureus (MRSA), despite the lack of controlled trials. In this double-blind, randomized study, the efficacy of intranasal mupirocin ointment versus that of placebo in reducing colonization and preventing infection was assessed among persistent carriers of S. aureus. Twice-daily treatment was given for 2 weeks, with a follow-up period of 6 months. Staphylococcal colonization rates were similar between residents at the Ann Arbor Veterans Affairs (VA) Extended Care Center, Michigan (33%), and residents at a community-based long-term care facility in Ann Arbor (36%), although those at the VA Center carried MRSA more often (58% vs. 35%; P p .017). After treatment, mupirocin had eradicated colonization in 93% of residents, whereas 85% of residents who received placebo remained colonized (P ! .001). At day 90 after study entry, 61% of the residents in the mupirocin group remained decolonized. Four patients did not respond to mupirocin therapy; 3 of the 4 had mupirocin-resistant S. aureus strains. Thirteen (86%) of 14 residents who became recolonized had the same pretherapy strain; no strain recovered during relapse was resistant to mupirocin. A trend toward reduction in infections was seen with mupirocin treatment. - S. aureus is significantly higher than it is for noncarriers, and infection is usually caused by the colonizing strain [5, 6]. Carriage of methicillin-resistant S. aureus (MRSA) has been shown to be a marker for increased risk of infection and mortality among LTCF residents [79]. Treatment of persistent staphylococcal carriage with the topical antibiotic mupirocin has been shown to decrease staphylococcal infections among patients undergoing hemodialysis and those who have undergone elective surgery [1014]. Several noncontrolled studies have shown that mupirocin alone or in combination with other measures decreases S. aureus colonization among residents of LTCFs [1518]. However, there are no controlled trials involving such individuals that have definitively shown that mupirocin decreases S. aureus colonization and infection. This study, which was performed in both community and Veterans Affairs (VA) LTCFs in Ann Arbor, Michigan, assessed whether a 2-week course of mupirocin therapy led to prolonged reduction in colonization and prevented S. aureus infection. Recolonization with S. aureus and acquisition of mupirocin resistance were evaluated. STUDY PARTICIPANTS AND METHODS Study population. The Ann Arbor VA Extended Care Center is a 50-bed facility attached to an acute care hospital. Residents are admitted for long-term care (10 beds), rehabilitation (10 beds), and geriatric evaluation (30 beds). Glacier Hills Nursing Center is a 163-bed community LTCF located within a few miles of the VA Medical Center. It has a 127-bed skilled nursing unit and a 36-bed dementia unit. Eligibility. All residents of the VA and community LTCFs were eligible. Appropriate informed consent was obtained, and guidelines for human experimentation and the conduct of clinical research were followed, as required by the University of Michigan and Veterans Affairs Ann Arbor Healthcare System institutional review boards. After obtaining written informed consent, specimens were obtained from the nares and, when present, wounds of all patients. Residents for whom culture results were positive for S. aureus on 2 consecutive cultures performed 2 weeks apart were considered persistent carriers and were enrolled into the treatment trial. Exclusion criteria. Residents were not enrolled if they were receiving systemic antibiotic therapy or topical antibiotic therapy for wounds, had active S. aureus infection, or were judged unable to cooperate with the study. Known hypersensitivity to mupirocin and the presence of large wounds (i.e., a surface area of 110 10 cm and a depth of 13 cm) were also exclusion factors. Residents who were initially found not to be carriers were screened again if they required admission to the hospital and then returned to the LTCF. Group assignment. Enrolled residents were randomly assigned to study groups by stratification according to LTCF type and presence of wounds. Randomization was performed separately on the basis of residence type and presence of wounds in blocks of 2 to assure that the number of patients assigned to study groups using these strata was equal. Investigators, nursing staff, and study participants were blinded to the treatment group. Treatment. Mupirocin therapy or placebo was administered twice daily for 14 days by study personnel who wore gloves after appropriate hand disinfection and who were blinded to results of microbiological tests. The study drugs were placed in identical containers labeled A or B by the study pharmacist. Mupirocin 2% ointment in polyethylene glycol (PEG) base or plain PEG ointment (placebo) was applied to each anterior naris, and the nose was massaged gently. Ointment was applied over wound surfaces in a thin layer. Samples were obtained from nares and wounds every other day during the treatment period. On day 15 of the studythe day after treatment endeda sample was obtained. Successive samples were obtained every week during the next 4 weeks, every 2 weeks for 2 months, and monthly for an additional 2.5 months, as long as the patient remained in the facility. Enrolled residents were observed for the development of staphylococcal infection during the same 6-month period, as long as they were residents of the facility. Permitted local wound care included whirlpool therapy, debridement, and application of hydrogen peroxide, Dakins solution (sodium hypochlorite 5.25%), and dressings. Wound therapy was provided before the study drug or placebo was administered. No topical or systemic antibiotic therapy with activity against S. aureus was allowed. Assessment. Demographic characteristics and risk factors for S. aureus colonization were assessed at study entry. Dimensions of decubitus or vascular ulcers, other wounds, skin conditions, and devices were recorded. Functional status was measured using a modified Katz scale [19]. Enrolled residents were monitored daily for S. aureus infection, on the basis of the Centers for Disease Control and Prevention definitions [20]. All cases were reviewed by a panel of 3 consultants who specialized in infectious diseases and geriatrics, all of whom were blinded to colonization data and treatment regimens. Outcomes. Outcomes were categorized as cure (i.e., no S. aureus was recovered from any site) or failure (i.e., persistence of S. aureus at the end of treatment or recoloniz (...truncated)