Outbreaks of extended spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review

Stapleton, Patrick; Murphy, Madeleine; McCallion, Naomi; Brennan, Maura; Cunney, Robert; Drew, Richard J.

doi:10.1136/archdischild-2015-308707

Cited by 95 publications

(88 citation statements)

References 75 publications

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“…Antibiotic resistance factors, conferring adaptation to the pathogenesis environment, are widely spread by horizontal gene transfer mechanisms like conjugation, transformation and transduction (Navarro (2006); Poirel et al (2009)). The persistent exposure of bacterial strains to a multitude of Beta lactams has induced dynamic and continuous pro-duction and mutation of Beta lactamases in these bacteria, expanding their activity even against the newly developed Beta lactam antibiotics (Stapleton et al (2016)). Thus, an important objective is to identify mutations in Beta lactamase genes conferring adaptation to human and animal hosts.…”

Section: 4mentioning

confidence: 99%

A New Paradigm for Identifying Reconciliation-Scenario Altering Mutations Conferring Environmental Adaptation

Zoller

Zehavi

Ziv-Ukelson

2020

Journal of Computational Biology

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An important goal in microbial computational genomics is to identify crucial events in the evolution of a gene that severely alter the duplication, loss and mobilization patterns of the gene within the genomes in which it disseminates. In this paper, we formalize this microbiological goal as a new pattern-matching problem in the domain of Gene tree and Species tree reconciliation, denoted "Reconciliation-Scenario Altering Mutation (RSAM) Discovery". We propose an O(m · n · k) time algorithm to solve this new problem, where m and n are the number of vertices of the input Gene tree and Species tree, respectively, and k is a user-specified parameter that bounds from above the number of optimal solutions of interest. The algorithm first constructs a hypergraph representing the k highest scoring reconciliation scenarios between the given Gene tree and Species tree, and then interrogates this hypergraph for subtrees matching a pre-specified RSAM Pattern. Our algorithm is optimal in the sense that the number of hypernodes in the hypergraph can be lower bounded by Ω(m · n · k). We implement the new algorithm as a tool, called RSAM-finder, and demonstrate its application to -the identification of RSAMs in toxins and drug resistance elements across a dataset spanning hundreds of species.

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Section: 4mentioning

confidence: 99%

A New Paradigm for Identifying Reconciliation-Scenario Altering Mutations Conferring Environmental Adaptation

Zoller

Zehavi

Ziv-Ukelson

2020

Journal of Computational Biology

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“…3 (length of <15 kb only is shown). (19,20). In our study, infection control practitioners took samples from incubators, air, the hands of doctors and nurses, objects and patient skin for bacterial culture.…”

Section: Pathogen-host Interactions and Genomic Islandsmentioning

confidence: 99%

Co-outbreak of ST37 and a novel ST3006 Klebsiella pneumoniae from multi-site infection in a neonatal intensive care unit: a retrospective study

Chen

et al. 2018

Preprint

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21 sequencing; Neonatal intensive care unit 22 23 2 Summary 24 Background: The spread of carbapenem resistance among Klebsiella pneumoniae (K. 25 pneumoniae) is a major public health problem, particularly in neonatal intensive care 26 units (NICUs).27Aim: To describe the nosocomial co-outbreak of ST37 and a new sequence type 28 ST3006 K. pneumoniae, causing catheter-related bloodstream infections in NICU. 29Methods: Fifteen strains of K. pneumoniae were isolated from seven neonates during 30 June 3-28, 2013, in a tertiary hospital neonatal intensive care unit in Fujian, China. 31Antimicrobial susceptibility was determined by the Vitek 2 system and micro-broth 32 dilution method. Multi-locus sequence typing (MLST) and pulsed-field gel 33 electrophoresis (PFGE) were used to analyse the genetic relatedness of isolates. 34Genome sequencing and gene function analyses were performed for investigating 35 pathogenicity and drug resistance and screening genomic islands. 36Findings: Two K. pneumoniae clones were identified from seven neonates with 37 multi-site infection, one ST37 strain and one new sequence type ST3006. 38Antimicrobial susceptibility testing revealed that the ST37 strain exhibited multi-drug 39 resistance and carbapenem resistance. The ST3006 strain was only resistant to 40 ampicillin-sulbactam, cefazolin, ceftriaxone. MLST and PFGE showed that 15 strains 41 were divided into three groups, with a high level of homology. Gene sequencing and 42 analysis indicated that KPN1343 harboured 12 resistance genes, 15 genomic islands 43 and 205 reduced virulence genes. KPN1344 harboured four resistance genes, 19 44 genomic islands and 209 reduced virulence genes. 45 Conclusion: Co-outbreak of K. pneumoniae involved two clones, ST36 and ST3006, 46 causing multi-site infection. Genome sequencing and analysis is an effective method 47 for studying bacterial resistance genes and their functions.48 49 50 Introduction 51 Klebsiella pneumonia, particularly multidrug resistant K. pneumoniae, is a 52 common and important pathogen in hospitals, posing a serious and urgent threat to 53 public health (1, 2). Neonates in the neonatal intensive care units often have 54 underlying conditions, such as prematurity, or the presence of indwelling catheters, a 55 history of antibiotic treatment and parenteral nutrition, which are risk factors for 56 infection (3). In addition, relaxed vigilance by doctors and nurses regarding 57 nosocomial infection promotes nosocomial infection outbreaks, with considerable 58 impact on neonatal treatment and prognosis, prolonged hospital stays, increased 59 hospital costs and mortality. 60 Nosocomial outbreaks in the neonatal intensive care unit are frequently reported 61(4-7); however, it is rare to isolate the same clonal pathogen from different sites in the 62 same patient. This study identified 15 K. pneumoniae strains isolated from sputum 63 specimens, blood specimens and umbilical vein catheter tips in seven neonates that 64 belonged to the two cloned strains ST37 and ST3006, which produced carb...

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“…Multi-drug resistant (MDR) Klebsiella pneumoniae is an increasing problem worldwide and is associated with poor patient outcomes, particularly in vulnerable groups such as neonates 1–7 . Whole genome sequencing (WGS) of clinical isolates has demonstrated the importance of the clonal spread in of K. pneumoniae in outbreak settings 2,8 , and colonization is known to substantially increase the risk of infection 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Transmission patterns of hyper-endemic multi-drug resistant Klebsiella pneumoniae in a Cambodian neonatal unit: a longitudinal study with whole genome sequencing

Smit

Stoesser

Pol

et al. 2017

Preprint

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BackgroundKlebsiella pneumoniae is an important and increasing cause of life-threatening disease in hospitalised neonates. Third generation cephalosporin resistance (3GC-R) is frequently a marker of multi-drug resistance, and can complicate management of infections. 3GC-R K. pneumoniae is hyper-endemic in many developing country settings, but its epidemiology is poorly understood and prospective studies of endemic transmission are lacking. We aimed to determine the transmission dynamics of 3GC-R K. pneumoniae in a newly opened neonatal unit (NU) in Cambodia.MethodsWe performed a prospective longitudinal study between September and November 2013. Rectal swabs from 37 consented patients were collected upon NU admission and every three days thereafter. Morphologically different colonies from swabs growing cefpodoxime-resistant K. pneumoniae were selected for whole-genome sequencing (WGS).Results32/37 (86%) patients screened positive for 3GC-R K. pneumoniae and 93 colonies from 119 swabs were sequenced. Isolates were resistant to a median of six (range 3-9) antimicrobials. WGS revealed high diversity; pairwise distances between isolates from the same patient were either 0-1 SNV or >1,000 SNVs; 19/32 colonized patients harboured K. pneumoniae colonies differing by >1000 SNVs. Diverse lineages accounted for 18 probable importations to the NU and nine probable transmission clusters involving 19/37 (51%) of screened patients. Median cluster size was 5 patients (range 3-9).ConclusionsThe epidemiology of 3GC-R K. pneumoniae was characterised by multiple introductions and a dense network of cross-infection, with half of screened neonates part of a transmission cluster. Efforts to reduce the 3GC-R K. pneumoniae disease burden should consider targeting both processes.

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Outbreaks of extended spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review

Cited by 95 publications

References 75 publications

A New Paradigm for Identifying Reconciliation-Scenario Altering Mutations Conferring Environmental Adaptation

A New Paradigm for Identifying Reconciliation-Scenario Altering Mutations Conferring Environmental Adaptation

Co-outbreak of ST37 and a novel ST3006 Klebsiella pneumoniae from multi-site infection in a neonatal intensive care unit: a retrospective study

Transmission patterns of hyper-endemic multi-drug resistant Klebsiella pneumoniae in a Cambodian neonatal unit: a longitudinal study with whole genome sequencing

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