Gram-Negative and Fungal Infections Following Mupirocin-based MRSA Decolonization in Neonates

Background: Decolonization with mupirocin, a topical antibiotic effective against gram-positive organisms, has been used to reduce methicillin resistant Staphylococcus aureus(MRSA) in neonatal intensive care units (NICUs). The narrow coverage of mupirocin may facilitate infection with non-targeted gram-negative and fungal pathogens. Our objective was to quantify the risk of gram-negative or fungal infection (GNFI) associated with mupirocin exposure among MRSA carriers in the NICU.

Methods: Retrospective, multi-centered cohort study of neonates admitted to three tertiary care NICUs from January 2007 to December 2014. MRSA-colonized patients were followed until the development of a clinically apparent GNFI or NICU discharge. Mupirocin exposure information was obtained from administrative databases and chart review. The outcome of GNFI was ascertained from cultures obtained during routine clinical care. Cox proportional hazards models were used to assess for differences in time to GNFI by mupirocin exposure status, adjusting for length of stay, sex, race, birth weight, and gestational age.

Results: 674 MRSA-positive neonates were identified during the study period, accounting for 32,073 patient-days at risk. Of these, 111 (16%) had a clinically apparent GNFI. Mupirocin was administered to 360 (53%) neonates. Mupirocin exposure was associated with an unadjusted 58% reduction in GNFI risk (RR=0.42, 95% CI: 0.29-0.60). Survival models that accounted for the time-varying nature of mupirocin exposure and compared neonates of the same length of stay, revealed an attenuated, protective association between mupirocin exposure and GNFI (HR=0.65, 95% CI: 0.42-1.00), when controlling for sex and race. A sub-analysis of study sites where birth weight and gestational age data were available did not show substantial changes in the effect of mupirocin on GNFI (HR=0.56, 95% CI: 0.31-1.00).

Conclusion: These data do not suggest an increased risk of GNFI in MRSA-colonized NICU patients treated with mupirocin. The time-varying nature of antibiotic exposures should be accounted for in models of infection risk. Future randomized studies are needed to assess whether mupirocin has a broader protective role beyond S. aureus infections.