Low Diversity in Nasal Microbiome Associated With Staphylococcus aureus Colonization and Bloodstream Infections in Hospitalized Neonates.

BACKGROUND: Staphylococcus aureus is a leading cause of infectious morbidity and mortality in neonates. Few data exist on the association of the nasal microbiome and susceptibility to neonatal S. aureus colonization and infection. METHODS: We performed 2 matched case-control studies (colonization cohort-neonates who did and did not acquire S. aureus colonization; bacteremia cohort-neonates who did [colonized neonates] and did not [controls] acquire S. aureus colonization and neonates with S. aureus bacteremia [bacteremic neonantes]). Neonates in 2 intensive care units were enrolled and matched on week of life at time of colonization or infection. Nasal samples were collected weekly until discharge and cultured for S. aureus, and the nasal microbiome was characterized using 16S rRNA gene sequencing. RESULTS: In the colonization cohort, 43 S. aureus-colonized neonates were matched to 82 controls. At 1 week of life, neonates who acquired S. aureus colonization had lower alpha diversity (Wilcoxon rank-sum test P < .05) and differed in beta diversity (omnibus MiRKAT P = .002) even after adjusting for birth weight (P = .01). The bacteremia cohort included 10 neonates, of whom 80% developed bacteremia within 4 weeks of birth and 70% had positive S. aureus cultures within a few days of bacteremia. Neonates with bacteremia had an increased relative abundance of S. aureus sequences and lower alpha diversity measures compared with colonized neonates and controls. CONCLUSIONS: The association of increased S. aureus abundance and decrease of microbiome diversity suggest the need for interventions targeting the nasal microbiome to prevent S. aureus disease in vulnerable neonates.

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

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.

The Association Between the Developing Nasal Microbiota of Hospitalized Neonates and Staphylococcus aureus Colonization.

BACKGROUND: Hospitalized neonates are at high risk for invasive Staphylococcus aureus infections. S. aureus nasal colonization often precedes infection. The nasal microbiota may preclude or support colonization. We aimed to characterize and compare the nasal microbiota of hospitalized neonates who acquire S. aureus colonization (cases) and those who do not acquire S. aureus (controls). METHODS: We obtained residual nares samples from hospitalized neonates who were screened weekly for S. aureus nasal colonization and treated with intranasal mupirocin if colonized. Eight cases were matched based on chronologic age and systemic antibiotic exposure to 7 controls. We extracted DNA, sequenced the V3-V4 region of the 16s rRNA gene, and performed taxonomic assignments. The bacterial species richness, relative abundance, and in silico predicted gene content were compared between cases and controls at 7 days before S. aureus acquisition, at the time of acquisition, and 7 days after acquisition and treatment. RESULTS: Common commensals including nondiphtheriae corynebacteria were more abundant in the nares of controls and Rothia mucilaginosa was more abundant in cases 7 days after intranasal mupirocin treatment than in cases 7 days before S. aureus acquisition. Controls and treated cases had a higher predicted abundance of genes contributing to the synthesis of certain antimicrobial compounds than in cases before S. aureus acquisition. CONCLUSIONS: Neonates without S. aureus nasal colonization had a higher abundance of bacterial species that antagonize S. aureus directly or by selecting for beneficial co-colonizers. These differences may inform novel S. aureus infection prevention strategies in high-risk infants.

Changing antibiotic resistance patterns for Staphylococcus aureus surgical site infections.

Beta-lactam antibiotics such as cefazolin are first-line agents for preoperative prophylaxis, whereas clindamycin is often administered to patients with a reported penicillin allergy. 1 Recent studies have reported increased resistance to clindamycin in Staphylococcus aureus (SA) isolates from both pediatric and adult populations, and these changes may have implications for surgical site infection (SSI) prophylaxis and empirical management. 2 , 3 Antibiotic resistance trends of SA isolates recovered from SSIs in adults in the United States have not been recently described.

Increasing Clindamycin and Trimethoprim-Sulfamethoxazole Resistance in Pediatric Staphylococcus aureus Infections.

The epidemiology of Staphylococcus aureus infection in children is dynamic. We conducted a retrospective observational study on pediatric clinical cultures, performed between 2005 and 2017, that grew S aureus to determine temporal trends in antibiotic resistance. Although methicillin resistance declined, clindamycin and trimethoprim-sulfamethoxazole resistance increased significantly, especially among community-onset isolates.