A Randomized Clinical Trial to Prevent Recurrent CA-MRSA Infection

Inclusion Criteria: * Is a member of Kaiser Permanente Southern California (KPSC) * Have at least 1 culture positive for MRSA in the prior 12 months and at least one skin infection in the prior 12 months. The culture(s) and/or skin infection(s) will: A. Be associated with mutually exclusive patient encounters that are separated by at least 21 days. The encounters include: outpatient visits to primary care provider; outpatient visits to emergency departments or urgent care facilities; inpatient hospitalizations (admission date is considered the encounter date) AND Each patient encounter defined in section A is associated with EITHER: B. EITHER receipt of a prescription (or course) of antibiotics for a clinical infection. OR C. A visit to an outpatient setting (including primary care provider visits, emergency department visits, phone consultations, and urgent care visits) for a skin or skin structure infection. * Age is 1 month or older * Ability and willingness to take intranasal medications, topical body washes, and environmental decontamination measures. * Ability and willingness of subject or legal guardian/representative to give written informed consent. * Ability and willingness to participate in the study according to treatment allocation even if not randomized to an active intervention. Exclusion Criteria: * Current residence in a KPSC-associated chronic care facility or other chronic-care facility (e.g., a rehabilitation facility or nursing home) * Receipt of hemodialysis or peritoneal dialysis in the prior 12 months * Any of the following severe underlying conditions: Organ transplantation, active or recent malignancy, cancer, or inflammatory disorder that has required (or would have require treatment) in the prior 12 months, with radiation therapy, surgery, chemotherapy, systemic immunomodulatory therapy (e.g., tumor necrosis factor (TNF)-alpha inhibitors for rheumatic and inflammatory diseases), or corticosteroid therapy (defined as \> 7.5 mg prednisone (or equivalent doses of a non-prednisone corticosteroid) daily for adults, or above physiologic levels of prednisone or other corticosteroid therapy daily for children). * Any of the following major surgical procedure in the prior 12 months: orthopedic procedure, cardiothoracic surgery, or abdominal surgery. * Use of the following drugs or procedures within 120 days prior to study entry: topical mupirocin (Bactroban or Bactroban Nasal), Chlorhexidine (e.g., Hibiclens or other branded or generic formulations) body washes, or environmental decontamination of the household with ethyl alcohol (e.g., Lysol Brand Disinfectant Spray for Kitchens or other branded or generic formulations), bleach or dilute bleach solutions, or similar regimens * Current use of systemic antibiotics used specifically to treat skin or skin structure infections, MRSA infections, or S. aureus infections. Patients on systemic therapy noted here must complete the systemic antibiotic therapy prior to enrollment. * Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements. * Current skin wound or lesion that is deeper than superficial layers of the skin (which is known to be a relative contraindication to topical Hibiclens). Subjects with deeper skin infection may be enrolled when their wound has healed sufficiently so that the wound is no deeper than the superficial skin layers * Known hypersensitivity or allergic reaction to either topical mupirocin or mupirocin-containing products (e.g., Bactroban or Bactroban Nasal), or chlorhexidine or chlorhexidine-containing (e.g., Hibiclens) topical washes or products containing chlorhexidine. * Concurrent use of other intranasal products (e.g., saline washes, topical decongestants, antihistamines, or anticholinergics). Patients who use these products who are willing to discontinue therapy for seven days while mupirocin is administered (if they are randomized to this medication) will be allowed to participate in consultation with the patient's provider. * Chronic skin conditions associated with hypersensitivity to using topical cleansers or preparations. * Known hypersensitivity among household members to the agents listed above, specifically mupirocin, chlorhexidine, and topical ethanol. * "Heavy" or excessive use of body decolonizing agents such as triclosan-containing soap or Phisohex, as determined by the Study Site Coordinator.