Randomized Placebo-Controlled Trial of Topical Mupirocin to Reduce Staphylococcus aureus Colonization in Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: To evaluate the efficacy of topical mupirocin in reducing Staphylococcus aureus colonization in infants in the neonatal intensive care unit (NICU). STUDY DESIGN: A prospective double-blind randomized controlled trial of mupirocin vs placebo in S aureus-colonized infants was conducted in a tertiary care NICU between October 2016 and December 2019. Weekly universal active surveillance with polymerase chain reaction screening identified colonized infants. Colonized infants received a 5-day course of mupirocin (mupirocin group) or petroleum jelly (control group). Repeat courses were given for additional positive screens. RESULTS: A total of 216 infants were enrolled; 205 were included in data analyses. Primary decolonization was more successful for mupirocin-treated infants (86 of 104 [83%]) than for controls (20 of 101; 20%) (P < .001). Although recurrent S aureus colonization occurred frequently (59 of 81 [73%] mupirocin-treated and 26 of 33 [79%] controls), subsequent decolonization remained more successful for mupirocin-treated infants than for controls (38 of 49 [78%] vs 2 of 21 [10%]; P < .001). Subgroup analyses of infants of ≤30 weeks' gestational age yielded similar results; decolonization occurred more often in mupirocin-treated infants compared with control infants (63 of 76 [83%] vs 13 of 74 [18%]; P < .001). Bacterial sterile site infections tended to be less frequent in mupirocin-treated infants compared with controls (2 of 104 [2%] vs 8 of 101 [8%]; P = .057). No invasive S aureus infections occurred in mupirocin-treated infants, but 50% of infections in controls were from S aureus, and 1 resulted in death. CONCLUSIONS: Universal active surveillance and targeted treatment with topical mupirocin is a successful decolonization strategy for NICU infants and may prevent S aureus infection. However, S aureus colonization frequently recurs, necessitating repeat treatment. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02967432.

Clinical and Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit in the Decade following Implementation of an Active Detection and Isolation Program.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent source of infection in the neonatal intensive care unit (NICU), often associated with significant morbidity. Active detection and isolation (ADI) programs aim to reduce transmission. We describe a comprehensive analysis of the clinical and molecular epidemiology of MRSA in an NICU between 2003 and 2013, in the decade following the implementation of an MRSA ADI program. Molecular analyses included strain typing by pulsed-field gel electrophoresis, mec and accessory gene regulator group genotyping by multiplex PCR, and identification of toxin and potential virulence factor genes via PCR-based assays. Of 8,387 neonates, 115 (1.4%) had MRSA colonization and/or infection. The MRSA colonization rate declined significantly during the study period from 2.2 to 0.5/1,000 patient days (linear time, P = 0.0003; quadratic time, P = 0.006). There were 19 cases of MRSA infection (16.5%). Few epidemiologic or clinical differences were identified between MRSA-colonized and MRSA-infected infants. Thirty-one different strains of MRSA were identified with a shift from hospital-associated to combined hospital- and community-associated strains over time. Panton-Valentine leukocidin-positive USA300 strains caused 5 of the last 11 infections. Staphylococcal cassette chromosome mec (SCCmec) types II and IVa and agr groups 1 and 2 were most predominant. One isolate possessed the gene for toxic shock syndrome toxin; none had genes for exfoliative toxin A or B. These results highlight recent trends in MRSA colonization and infection and the corresponding changes in molecular epidemiology. Continued vigilance for this invasive pathogen remains critical, and specific attention to the unique host, the neonate, and the distinct environment, the NICU, is imperative.

Novel FOXF1 deep intronic deletion causes lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins.

Haploinsufficiency of FOXF1 causes an autosomal dominant neonatally lethal lung disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). We identified novel 0.8-kb deletion within the 1.4-kb intron of FOXF1 in a deceased newborn diagnosed with ACDMPV. The deletion arose de novo on the maternal copy of the chromosome 16, and did not affect FOXF1 minigene splicing tested in lung fibroblasts. However, FOXF1 transcript level in the ACDMPV peripheral lung tissue was reduced by almost 40%. We found that, in an in vitro reporter assay, the FOXF1 intron exhibited moderate transcriptional enhancer activity, correlating with the presence of binding sites for expression regulators CTCF and CEBPB, whereas its truncated copy, which lost major CTCF and CEBPB-binding sites, inhibited the FOXF1 promoter. Our data further emphasize the importance of testing the non-protein coding regions of the genome currently not covered by diagnostic chromosomal microarray analyses or whole-exome sequencing.

Experiences of a Regional Quality Improvement Collaborative to Reduce Unplanned Extubations in the Neonatal Intensive Care Unit.

BACKGROUND: Unplanned extubations (UEs) occur frequently in the neonatal intensive care unit (NICU). These events can be associated with serious short-term and long-term morbidities and increased healthcare costs. Most quality improvement (QI) initiatives focused on UE prevention have concentrated efforts within individual NICUs. METHODS: We formed a regional QI collaborative involving the four regional perinatal center (RPC) NICUs in upstate New York to reduce UEs. The collaborative promoted shared learning and targeted interventions specific to UE classification at each center. RESULTS: There were 1167 UEs overall during the four-year project. Following implementation of one or more PDSA cycles, the combined UE rate decreased by 32% from 3.7 to 2.5 per 100 ventilator days across the collaborative. A special cause variation was observed for the subtype of UEs involving removed endotracheal tubes (rETTs), but not for dislodged endotracheal tubes (dETTs). The center-specific UE rates varied; only two centers observed significant improvement. CONCLUSIONS: A collaborative approach promoted knowledge sharing and fostered an overall improvement, although the individual centers' successes varied. Frequent communication and shared learning experiences benefited all the participants, but local care practices and varying degrees of QI experience affected each center's ability to successfully implement potentially better practices to prevent UEs.

Methicillin-resistant Staphylococcus aureus in the neonatal intensive care unit.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent source of infections affecting premature and critically ill infants in neonatal intensive care units (NICUs). Neonates are particularly vulnerable to colonization and infection with MRSA, and many studies have attempted to identify risk factors that predispose certain infants to its acquisition to discover potential areas for clinical intervention. In addition, epidemiologic assessment of transmission patterns and molecular analysis of changes in the characteristics of MRSA strains over time have helped clarify additional factors affecting MRSA infections in the NICU. Numerous strategies for prevention and eradication have been used with variable rates of success. Despite these interventions, MRSA remains a significant source of morbidity in the NICU population.