Dataset Information

Whole-genome sequencing to explore nosocomial transmission and virulence in neonatal methicillin-susceptible Staphylococcus aureus bacteremia.

ABSTRACT: BACKGROUND:Neonatal Staphylococcus aureus (S. aureus) bacteremia is an important cause of morbidity and mortality. In this study, we examined whether methicillin-susceptible S. aureus (MSSA) transmission and genetic makeup contribute to the occurrence of neonatal S. aureus bacteremia. METHODS:A retrospective, single-centre study was performed. All patients were included who suffered from S. aureus bacteremia in the neonatal intensive care unit (NICU), Erasmus MC-Sophia, Rotterdam, the Netherlands, between January 2011 and November 2017. Whole-genome sequencing (WGS) was used to characterize the S. aureus isolates, as was also done in comparison to reference genomes. Transmission was considered likely in case of genetically indistinguishable S. aureus isolates. RESULTS:Excluding coagulase-negative staphylococci (CoNS), S. aureus was the most common cause of neonatal bacteremia. Twelve percent (n?=?112) of all 926 positive blood cultures from neonates grew S. aureus. Based on core genome multilocus sequence typing (cgMLST), 12 clusters of genetically indistinguishable MSSA isolates were found, containing 33 isolates in total (2-4 isolates per cluster). In seven of these clusters, at least two of the identified MSSA isolates were collected within a time period of one month. Six virulence genes were present in 98-100% of all MSSA isolates. In comparison to S. aureus reference genomes, toxin genes encoding staphylococcal enterotoxin A (sea) and toxic shock syndrome toxin 1 (tsst-1) were present more often in the genomes of bacteremia isolates. CONCLUSION:Transmission of MSSA is a contributing factor to the occurrence of S. aureus bacteremia in neonates. Sea and tsst-1 might play a role in neonatal S. aureus bacteremia.

SUBMITTER: Slingerland BCGC

PROVIDER: S-EPMC7036242 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Whole-genome sequencing to explore nosocomial transmission and virulence in neonatal methicillin-susceptible Staphylococcus aureus bacteremia.

Slingerland Bibi C G C BCGC Vos Margreet C MC Bras Willeke W Kornelisse René F RF De Coninck Dieter D van Belkum Alex A Reiss Irwin K M IKM Goessens Wil H F WHF Klaassen Corné H W CHW Verkaik Nelianne J NJ

Antimicrobial resistance and infection control 20200222 1

<h4>Background</h4>Neonatal Staphylococcus aureus (S. aureus) bacteremia is an important cause of morbidity and mortality. In this study, we examined whether methicillin-susceptible S. aureus (MSSA) transmission and genetic makeup contribute to the occurrence of neonatal S. aureus bacteremia.<h4>Methods</h4>A retrospective, single-centre study was performed. All patients were included who suffered from S. aureus bacteremia in the neonatal intensive care unit (NICU), Erasmus MC-Sophia, Rotterdam, ...[more]

PMID: 32087747

Similar Datasets

Project description:Several studies have shown that patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) have worse outcomes than those with bacteremia caused by methicillin-susceptible S. aureus (MSSA). However, only a limited number of studies have stratified the MRSA isolates into healthcare-associated (HA-) and community-associated (CA-) MRSA strains in such a comparison. This three-year retrospective cohort study, enrolling adult patients with nosocomial S. aureus bacteremia (SAB), was designed to investigate whether CA-MRSA and/or HA-MRSA strains were associated with different outcomes in comparison to MSSA in such a setting. The drug susceptibilities and staphylococcal cassette chromosome mec (SCCmec) types were determined for all of the causative isolates available. The MRSA bacteremia was further categorized into those caused by CA-MRSA strains (CA-MRSA-S bacteremia) when the causative isolates carried the type IV or V SCCmec element, those caused by HA-MRSA strains (HA-MRSA-S bacteremia) when the isolates carried the type I, II, or III SCCmec element, or unclassified MRSA bacteremia when the isolates were not available. The relevant demographic, clinical, and laboratory data were collected by reviewing the patients' charts. The primary outcome was all-cause in-hospital mortality. A total of 353 patients were studied. The overall in-hospital mortality rate was 32.6%, with 23.3% in MSSA, 30.5% in CA-MRSA-S, 47.5% in HA-MRSA-S, and 35.3% in unclassified MRSA bacteremia, respectively. The multivariate analysis showed that HA-MRSA-S, but not CA-MRSA-S, bacteremia was associated with a significantly worse outcome compared with MSSA. The other risk factors independently associated with all-cause in-hospital mortality included the Charlson co-morbidity index, septic shock, thrombocytopenia, and persistent bacteremia. Resistance to linezolid and daptomycin was found among the MRSA isolates. The present study showed that bacteremia caused by HA-MRSA-S, but not CA-MRSA-S, was an independent risk factor for all-cause in-hospital mortality in patients with nosocomial SAB. Continuous monitoring regarding the susceptibilities of MRSA to linezolid and daptomycin is necessary.

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:Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Dataset Information

Whole-genome sequencing to explore nosocomial transmission and virulence in neonatal methicillin-susceptible Staphylococcus aureus bacteremia.

Publications

Whole-genome sequencing to explore nosocomial transmission and virulence in neonatal methicillin-susceptible Staphylococcus aureus bacteremia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets