Effect of Treating Parents Colonized With Staphylococcus aureus on Transmission to Neonates in the Intensive Care Unit: A Randomized Clinical Trial

Abstract

Importance: Staphylococcus aureus is a leading cause of health care-associated infections in the neonatal intensive care unit (NICU). Parents may expose neonates to S aureus colonization, a well-established predisposing factor to invasive S aureus disease.

Objective: To test whether treating parents with intranasal mupirocin and topical chlorhexidine compared with placebo would reduce transmission of S aureus from parents to neonates.

Design, setting, and participants: Double-blinded randomized clinical trial in 2 tertiary NICUs in Baltimore, Maryland. Neonates (n = 236) with S aureus-colonized parent(s) were enrolled. The study period was November 7, 2014, through December 13, 2018.

Interventions: Parents were assigned to intranasal mupirocin and 2% chlorhexidine-impregnated cloths (active treatment, n = 117) or petrolatum intranasal ointment and nonmedicated soap cloths (placebo, n = 119) for 5 days.

Main outcomes and measures: The primary end point was concordant S aureus colonization by 90 days, defined as neonatal acquisition of an S aureus strain that was the same strain as a parental strain at time of screening. Secondary outcomes included neonatal acquisition of any S aureus strain and neonatal S aureus infections.

Results: Among 236 randomized neonates, 208 were included in the analytic sample (55% male; 76% singleton births; mean birth weight, 1985 g [SD, 958 g]; 76% vaginal birth; mean parent age, 31 [SD, 7] years), of whom 18 were lost to follow-up. Among 190 neonates included in the analysis, 74 (38.9%) acquired S aureus colonization by 90 days, of which 42 (56.8%) had a strain concordant with a parental baseline strain. In the intervention and placebo groups, 13 of 89 neonates (14.6%) and 29 of 101 neonates (28.7%), respectively, acquired concordant S aureus colonization (risk difference, -14.1% [95% CI, -30.8% to -3.9%]; hazard ratio [HR], 0.43 [95.2% CI, 0.16 to 0.79]). A total of 28 of 89 neonates (31.4%) in the intervention group and 46 of 101 (45.5%) in the control group acquired any S aureus strain (HR, 0.57 [95% CI, 0.31 to 0.88]), and 1 neonate (1.1%) in the intervention group and 1 neonate (1.0%) in the control group developed an S aureus infection before colonization. Skin reactions in parents were common (4.8% intervention, 6.2% placebo).

Conclusions and relevance: In this preliminary trial of parents colonized with S aureus, treatment with intranasal mupirocin and chlorhexidine-impregnated cloths compared with placebo significantly reduced neonatal colonization with an S aureus strain concordant with a parental baseline strain. However, further research is needed to replicate these findings and to assess their generalizability.

Trial registration: ClinicalTrials.gov Identifier: NCT02223520.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Milstone reported receiving grants from the Centers for Disease Control and Prevention, the National Institutes of Health (NIH), and Sage Products Inc and receiving personal fees from Becton Dickinson. Dr Cosgrove reported receiving personal fees from Novartis, Theravance, and Basilea. Dr Carroll reported receiving grants from NIH, Singulex Inc, Curetis Inc, Accelerate Inc, and GenMark and receiving personal fees from Pattern Diagnostics, GenMark, and Becton Dickinson. No other disclosures were reported.

Figures

Figure 1.. Flow of the Treating Parents to Reduce NICU Transmission of Staphylococcus aureus (TREAT PARENTS) Trial, November 2014 to October 2018

NICU indicates neonatal intensive care unit.

Figure 2.. Kaplan-Meier Curves for Staphylococcus aureus Acquisition

A, Time to concordant S aureus acquisition (primary outcome). The confidence level for the primary outcome was 95.2%, which accounted for the 2 preplanned interim analyses. B, Time to any S aureus colonization. Time at risk is calculated the same way for panels A and B; namely, time from randomization to first of S aureus acquisition, collection of last culture, or 90 days. Median time at risk, 14 (interquartile range [IQR], 8-23) days for the intervention group and 9 (IQR, 8-20) days for the placebo group. X-axes truncated because a small number of neonates remained at risk after 40 days. Vertical ticks on curves indicate neonates censored at the time of last culture (surveillance or neonatal intensive care unit discharge). Most neonates had their first follow-up culture collected 1 week after randomization, illustrated by the few events occurring before day 7. The bias-corrected and accelerated bootstrap confidence interval accounts for bias and skewness in the bootstrap distribution. The bias correction is related to the proportion of bootstrap estimates that are less than the observed statistic; the acceleration parameter is proportional to the skewness of the bootstrap distribution and is estimated using a jackknife method.