Dataset Information

Risk factors for methicillin-resistant Staphylococcus aureus colonization in a level-IV neonatal intensive care unit: a retrospective study.

ABSTRACT:

Objective

To identify risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) colonization in neonatal patients during an MRSA outbreak to minimize future outbreaks.

Design

Retrospective case-control study.

Setting

Level-IV neonatal intensive care unit (NICU) at Copenhagen University Hospital, Rigshospitalet, Denmark.

Patients

Neonates with either MRSA or methicillin-susceptible Staphylococcus aureus (MSSA).

Methods

Methicillin-resistant Staphylococcus aureus-positive neonates were matched with those colonized or infected with MSSA in a 1:1 ratio. The control group was selected from clinical samples, whereas MRSA-positive neonates were identified from clinical samples or from screening. A total of 140 characteristics were investigated to identify risk factors associated with MRSA acquisition. The characteristics were categorized into three categories: patient, unit, and microbiological characteristics.

Results

Out of 1,102 neonates screened for MRSA, between December 2019 and January 2022, 33 were MRSA positive. They were all colonized with an MRSA outbreak clone (spa type t127) and were included in this study. Four patients (12%) had severe infection. Admission due to respiratory diseases, need for intubation, need for peripheral venous catheters, admission to shared rooms with shared toilets and bath facilities in the aisles, and need for readmission were all correlated with later MRSA colonization (P < 0.05).

Conclusion

We identified clinically relevant diseases, procedures, and facilities that predispose patients to potentially life-threatening MRSA infections. A specific MRSA reservoir remains unidentified; however, these findings have contributed to crucial changes in our NICU to reduce the number of MRSA infections and future outbreaks.

SUBMITTER: Galuszka JE

PROVIDER: S-EPMC10654989 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Risk factors for methicillin-resistant <i>Staphylococcus aureus</i> colonization in a level-IV neonatal intensive care unit: a retrospective study.

Galuszka Julia Elzbieta JE Thomsen Kim K Knudsen Jenny Dahl JD Stenkjaer Rikke Louise RL Nielsen Rikke R Nielsen Karen Leth KL Petersen Andreas A Holzknecht Barbara Juliane BJ Bartels Mette Damkjaer MD Breindahl Morten M Aunsholt Lise L

Antimicrobial stewardship & healthcare epidemiology : ASHE 20231031 1

<h4>Objective</h4>To identify risk factors associated with methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) colonization in neonatal patients during an MRSA outbreak to minimize future outbreaks.<h4>Design</h4>Retrospective case-control study.<h4>Setting</h4>Level-IV neonatal intensive care unit (NICU) at Copenhagen University Hospital, Rigshospitalet, Denmark.<h4>Patients</h4>Neonates with either MRSA or methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA).<h4>Methods</h4>Methic ...[more]

PMID: 38028927

Similar Datasets

Project description:Despite infection prevention efforts, neonatal intensive care unit (NICU) patients remain at risk of Methicillin-resistant Staphylococcus aureus (MRSA) infection. Modes of transmission for healthcare-associated (HA) and community-associated (CA) MRSA remain poorly understood and may vary by genotype, hindering the development of effective prevention and control strategies. From 2008-2010, all patients admitted to a level III NICU were screened for MRSA colonization, and all available isolates were spa-typed. Spa-type t008, the most prevalent CA- genotype in the United States, spa-type t045, a HA- related genotype, and a convenience sample of strains isolated from 2003-2011, underwent whole-genome sequencing and phylodynamic analysis. Patient risk factors were compared between colonized and noncolonized infants, and virulence and resistance genes compared between spa-type t008 and non-t008 strains. Epidemiological and genomic data were used to estimate MRSA importations and acquisitions through transmission reconstruction. MRSA colonization was identified in 9.1% (177/1940) of hospitalized infants and associated with low gestational age and birth weight. Among colonized infants, low gestational age was more common among those colonized with t008 strains. Our data suggest that approximately 70% of colonizations were the result of transmission events within the NICU, with the remainder likely to reflect importations of "outside" strains. While risk of transmission within the NICU was not affected by spa-type, patterns of acquisition and importation differed between t008 and t045 strains. Phylodynamic analysis showed the effective population size of spa-type t008 has been exponentially increasing in both community and hospital, with spa-type t008 strains possessed virulence genes not found among t045 strains; t045 strains, in contrast, appeared to be of more recent origin, with a possible hospital source. Our data highlight the importance of both intra-NICU transmission and recurrent introductions in maintenance of MRSA colonization within the NICU environment, as well as spa-type-specific differences in epidemiology.

Project description:ImportanceStaphylococcus aureus is one of the leading causes of infections in neonatal intensive care units (NICUs). Most studies in this patient group focus on methicillin-resistant S aureus or the outbreak setting, whereas data for methicillin-susceptible S aureus are limited.ObjectivesTo identify risk factors for S aureus colonization and infections in hospitalized newborns and to investigate S aureus transmission and its dynamics in a nonoutbreak setting.Design, setting, and participantsThis monocentric cohort study in a tertiary NICU in Heidelberg, Germany, enrolled all hospitalized neonates (n = 590) with at least 1 nasal screening swab positive for S aureus. Data were collected from January 1, 2018, to December 31, 2019.ExposuresWeekly screening for S aureus colonization was performed for all newborns until discharge.Main outcomes and measuresThe primary end point was any S aureus infection until hospital discharge. Transmission of S aureus and performance of routine typing to detect transmissions were defined as the secondary outcomes of the study.ResultsIn total, 590 newborns were enrolled (276 [46.8%] female and 314 [53.2%] male; 220 [37.3%] with birthweight <1500 g; 477 [80.8%] preterm; 449 [76.1%] singletons; 419 [71.5%] delivered via cesarean section). The median length of stay was 26 (range, 10-62) days. Overall, 135 infants (22.9%) were colonized by S aureus at some time during their hospital stay. The median time to first detection was 17 (interquartile range, 11-37) days. The overall incidence of S aureus infection was 1.7% (10 of 590). Low birth weight (<1500 g [odds ratio, 9.3; 95% CI, 5.9-14.6; P < .001]) and longer hospital stay (odds ratio, 2.3; 95% CI, 1.9-2.7; P < .001) were associated with colonization. Nasal carriage was significantly associated with S aureus infection (odds ratio, 8.2; 95% CI, 2.1-32.3; P = .002). A total of 123 of 135 colonization isolates were sequenced. All recoverable infection isolates (4 of 7) of newborns with colonization were genetically identical to the colonizing isolate. Whole-genome sequencing indicated 23 potential transmission clusters.Conclusions and relevanceThe findings of this cohort study suggest that nasal colonization is a relevant risk factor for S aureus infection in a nonoutbreak NICU setting. In colonized newborns, infection and colonization isolates were genetically identical, suggesting that eradication of colonization may be a useful measure to prevent infection. Further investigations are necessary to validate and assess the generalizability of our findings.

Project description:Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) is a component of our neonatal intensive care unit (NICU) infection prevention efforts. Recent atypical trends prompted review of 42 suspected MRSA isolates. Species identification was confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and methicillin resistance was reevaluated by PBP2a lateral flow assay, cefoxitin/oxacillin susceptibility testing, mecA and mecC PCR, and six commercially available MRSA detection agars. All isolates were confirmed S. aureus, but only eight were MRSA (cefoxitin resistant, PBP2a positive, mecA positive, growth on all MRSA screening agars). One MRSA isolate was cefoxitin susceptible but PBP2a and mecA positive, and the remaining 33 were cefoxitin susceptible, PBP2a negative, and mecA negative; interestingly, these isolates grew inconsistently across MRSA screening agars and had susceptibility profiles consistent with that of borderline oxacillin-resistant S. aureus (BORSA). Comparative genomic analyses found these BORSA isolates to be phylogenetically diverse and not representative of clonal expansion or shared gene content, though clones of two NICU strains were infrequently observed over 8 months. We identified 6 features-substitutions and truncations in PBP2, PBP4, and GdpP and beta-lactamase hyperproduction-that were used to generate a random forest classifier to distinguish BORSA from methicillin-susceptible S. aureus (MSSA) in our cohort. Our model demonstrated a robust ability to predict the BORSA phenotype among isolates collected across two continents (validation area under the curve [AUC], 0.902). Taking these findings together, we observed an unexpected prevalence of BORSA in our NICU, BORSA misclassification by existing MRSA screening methods, and markers that are together discriminatory for BORSA and MSSA within our cohort. This work has implications for epidemiological reporting of MRSA rates for centers using different screening methods. IMPORTANCE In this study, we found a high prevalence of Staphylococcus aureus isolates exhibiting a borderline oxacillin resistance phenotype (BORSA) in our neonatal intensive care unit (NICU) serendipitously due to the type of MRSA screening agar used by our laboratory for active surveillance cultures. Subsequent phenotypic and molecular characterization highlighted an unexpected prevalence and variability of BORSA isolates. Through whole-genome sequencing, we interrogated core and accessory genome content and generated a random forest classification model to identify mutations and truncations in the PBP2, PBP4, and GdpP proteins and beta-lactamase hyperproduction, which correlated with BORSA and MSSA phenotypes among S. aureus clinical isolates collected across two continents. In consideration of these findings, this work will help clinical microbiology laboratories and clinicians identify MRSA screening shortfalls and draw attention to the non-mecA-mediated BORSA phenotype.

Project description:Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) are well described in the neonatal intensive care unit (NICU) setting. Genomics has revolutionized the investigation of such outbreaks; however, to date, this has largely been completed retrospectively and has typically relied on short-read platforms. In 2022, our laboratory established a prospective genomic surveillance system using Oxford Nanopore Technologies sequencing for rapid outbreak detection. Herein, using this system, we describe the detection and control of an outbreak of sequence-type (ST)97 MRSA in our NICU. The outbreak was identified 13 days after the first MRSA-positive culture and at a point where there were only two known cases. Ward screening rapidly defined the extent of the outbreak, with six other infants found to be colonized. There was minimal transmission once the outbreak had been detected and appropriate infection control measures had been instituted; only two further ST97 cases were detected, along with three unrelated non-ST97 MRSA cases. To contextualize the outbreak, core-genome single-nucleotide variants were identified for phylogenetic analysis after de novo assembly of nanopore data. Comparisons with global (n=45) and national surveillance (n=35) ST97 genomes revealed the stepwise evolution of methicillin resistance within this ST97 subset. A distinct cluster comprising nine of the ten ST97-IVa genomes from the NICU was identified, with strains from 2020 to 2022 national surveillance serving as outgroups to this cluster. One ST97-IVa genome presumed to be part of the outbreak formed an outgroup and was retrospectively excluded. A second phylogeny was created using Illumina sequencing, which considerably reduced the branch lengths of the NICU isolates on the phylogenetic tree. However, the overall tree topology and conclusions were unchanged, with the exception of the NICU outbreak cluster, where differences in branch lengths were observed. This analysis demonstrated the ability of a nanopore-only prospective genomic surveillance system to rapidly identify and contextualize an outbreak of MRSA in a NICU.