Randomized Controlled Trial of Mupirocin to Reduce Staphylococcus Aureus Colonization in Infants Hospitalized in a Neonatal Intensive Care Unit

This randomized controlled trial of mupirocin treatment of MSSA- and MRSA-colonized infants aims to determine whether or not mupirocin treatment results in S. aureus decolonization in affected NICU patients. MSSA- or MRSA-colonized patients who enroll in the study will be randomized to either a treatment group (treatment with mupirocin) or control group (treatment with placebo). A combination of active surveillance and targeted decolonization will qualitatively and quantitatively enable assessment of any changes in S. aureus colonization in study patients. The primary outcome measure will be the number of MSSA/MRSA patient colonization days in the treatment versus control groups. Secondary outcome measures will include the proportion of persistently colonized patients at each subsequent weekly screening interval in the treatment versus control group, incidence and timing of MSSA/MRSA recolonization in the treatment group, incidence of invasive infections with S. aureus in the treatment versus control group, incidence of mupirocin-resistance in treatment versus control group, and incidence of MSSA/MRSA colonization after NICU discharge in the treatment versus control group.

STUDY PROCEDURES

Current standard of care in the NICU includes active universal screening of all admitted patients weekly for MSSA/MRSA colonization and contact precautions for MRSA-positive patients. No universal or targeted decolonization procedures are currently utilized. NICU patients who screen positive for MSSA/MRSA colonization will be approached for participation in this study and consent will be obtained from a parent within 2 days of the initial positive screening result by a neonatologist. At time of enrollment, patients will be randomized to either the treatment or control group. The pharmacy team will assign randomization; all NICU staff will be blinded to the patient's study group assignments throughout their admission. The treatment group will receive mupirocin ointment applied twice daily inside the nares and to the skin around the umbilicus for five days. The control group will receive a placebo ointment (petroleum jelly) applied in an identical fashion. The control group will not receive mupirocin ointment at any time, regardless of colonization status. If patients have recurrent positive MSSA/MRSA screens during the study, they may receive additional identical courses of treatment with either mupirocin or placebo based on their study group assignment.

The mupirocin and placebo petroleum jelly ointments will be supplied by the Crouse Hospital pharmacy and sent to the NICU daily for twice daily application by the nursing staff. Both groups will receive a ½ inch ribbon topical application of mupirocin or petroleum jelly ointment according to their assignment around the umbilicus and a ½ inch ribbon inside each nare. The neonatal nursing staff will receive appropriate education regarding the application technique and study protocol prior to study initiation. The cost of the mupirocin and placebo ointments will be paid for by Neonatal Associates of Central New York, LLC, and patients will not receive any fee for this service.

Colonization with MSSA/MRSA will be screened weekly on Mondays, in line with current Crouse Hospital NICU standard of care. MSSA/MRSA screening is performed by polymerase chain reaction (PCR). Sample collection involves swabbing an infant's nares, umbilicus, and groin with a cotton-tipped applicator. The swab tip is then sent to the Crouse Hospital Laboratory for Staphylococcus species identification. There will be no additional costs associated with these screenings, as this is already standard of care. Mupirocin resistance will be assessed by disk diffusion assay with E-test methodology to determine MICs. The costs associated with this additional test will be paid for by Neonatal Associates of Central New York, LLC, and patients will not receive any fee for this service. An additional MSSA/MRSA screen will be performed approximately 2 months after discharge at a patient's primary care physicians' office visit. Sample collection procedures will be identical to the screens performed at Crouse, and the screens will be sent to Laboratory Alliance of Central New York's Microbiology Department for testing. Results will be made available to the principal investigator. The costs associated with this additional outpatient screening test will be paid for by Neonatal Associates of Central New York, LLC, and patients will not receive any fee for this service.