Dataset Information

A mathematical model and inference method for bacterial colonization in hospital units applied to active surveillance data for carbapenem-resistant enterobacteriaceae.

ABSTRACT: Widespread use of antibiotics has resulted in an increase in antimicrobial-resistant microorganisms. Although not all bacterial contact results in infection, patients can become asymptomatically colonized, increasing the risk of infection and pathogen transmission. Consequently, many institutions have begun active surveillance, but in non-research settings, the resulting data are often incomplete and may include non-random testing, making conventional epidemiological analysis problematic. We describe a mathematical model and inference method for in-hospital bacterial colonization and transmission of carbapenem-resistant Enterobacteriaceae that is tailored for analysis of active surveillance data with incomplete observations. The model and inference method make use of the full detailed state of the hospital unit, which takes into account the colonization status of each individual in the unit and not only the number of colonized patients at any given time. The inference method computes the exact likelihood of all possible histories consistent with partial observations (despite the exponential increase in possible states that can make likelihood calculation intractable for large hospital units), includes techniques to improve computational efficiency, is tested by computer simulation, and is applied to active surveillance data from a 13-bed rehabilitation unit in New York City. The inference method for exact likelihood calculation is applicable to other Markov models incorporating incomplete observations. The parameters that we identify are the patient-patient transmission rate, pre-existing colonization probability, and prior-to-new-patient transmission probability. Besides identifying the parameters, we predict the effects on the total prevalence (0.07 of the total colonized patient-days) of changing the parameters and estimate the increase in total prevalence attributable to patient-patient transmission (0.02) above the baseline pre-existing colonization (0.05). Simulations with a colonized versus uncolonized long-stay patient had 44% higher total prevalence, suggesting that the long-stay patient may have been a reservoir of transmission. High-priority interventions may include isolation of incoming colonized patients and repeated screening of long-stay patients.

SUBMITTER: Ong KM

PROVIDER: S-EPMC7660488 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A mathematical model and inference method for bacterial colonization in hospital units applied to active surveillance data for carbapenem-resistant enterobacteriaceae.

Ong Karen M KM Phillips Michael S MS Peskin Charles S CS

PloS one 20201112 11

Widespread use of antibiotics has resulted in an increase in antimicrobial-resistant microorganisms. Although not all bacterial contact results in infection, patients can become asymptomatically colonized, increasing the risk of infection and pathogen transmission. Consequently, many institutions have begun active surveillance, but in non-research settings, the resulting data are often incomplete and may include non-random testing, making conventional epidemiological analysis problematic. We des ...[more]

PMID: 33180781

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Project description:BackgroundFecal colonization by carbapenem-resistant Enterobacteriaceae (CRE) can be the main reservoir for transmission of these resistant organisms especially in the Intensive Care Units (ICUs).AimThis study was conducted to evaluate the rate of rectal carriage and molecular characterization of CRE in patients hospitalized in the ICUs of 2 major hospitals (Adan and Mubarak Al Kabeer Hospitals) in Kuwait.Materials and methodsRectal swabs were collected from all patients at admission, 48 h after admission and once weekly from April 2017- March 2018. Initial CRE screening was carried out on MacConkey agar on which meropenem disc 10μg was placed. Identification of isolates was by API 20E. Susceptibility testing was performed using the E-test method. Polymerase chain reaction (PCR) was used to detect the carbapenemase-encoding genes. Clonal relationship was investigated by pulsed-field electrophoresis (PFGE). Genes of blaOXA-181 and blaNDM-5-carrying plasmids were detected in some strains.ResultsA total of 590 patients were recruited into the study. Of these, 58 were positive for CRE, giving a prevalence of 9.8%; 25/320 (7.8%) in Adan and 33/270 (12.2%) in Mubarak Al Kabeer Hospitals. All isolates were resistant to multiple antibiotics. Resistance rates to colistin and tigecycline were 17% and 83%, respectively. Single genes of blaOXA-181 were detected in isolates from 38 (65.5%) out of 58 patients and in 5 patients colonized by blaOXA-48-positive CRE. A combination of 2 genes was detected in 12 isolates; 5 blaKPC-2 and blaOXA-181, 4 blaVIM-1 and blaOXA-181, and 3 blaNDM-5 and blaOXA-181. PFGE showed an overall level of similarity of 38%. Southern hybridization studies localized the blaOXA-181 and blaNDM-5 genes to a large plasmid of 200kb in 3 K. pneumoniae isolates and a small plasmid of 80kb in 2 E. coli isolates, respectively.ConclusionThe prevalence of CRE colonization in the 2 hospital ICUs was relatively high and the emergence of blaOXA-181-mediated CRE is a cause for concern as there is the possibility of rapid horizontal spread among hospital patients in Kuwait. Active surveillance of CRE in the ICUs is highly recommended to stem its spread.

Project description:UnlabelledCarbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health concern. Rapid identification of the resistance genes, their mobilization capacity, and strains carrying them is essential to direct hospital resources to prevent spread and improve patient outcomes. Whole-genome sequencing allows refined tracking of both chromosomal traits and associated mobile genetic elements that harbor resistance genes. To enhance surveillance of CREs, clinical isolates with phenotypic resistance to carbapenem antibiotics underwent whole-genome sequencing. Analysis of 41 isolates of Klebsiella pneumoniae and Enterobacter cloacae, collected over a 3-year period, identified K. pneumoniae carbapenemase (KPC) genes encoding KPC-2, -3, and -4 and OXA-48 carbapenemases. All occurred within transposons, including multiple Tn4401 transposon isoforms, embedded within more than 10 distinct plasmids representing incompatibility (Inc) groups IncR, -N, -A/C, -H, and -X. Using short-read sequencing, draft maps were generated of new KPC-carrying vectors, several of which were derivatives of the IncN plasmid pBK31551. Two strains also had Tn4401 chromosomal insertions. Integrated analyses of plasmid profiles and chromosomal single-nucleotide polymorphism (SNP) profiles refined the strain patterns and provided a baseline hospital mobilome to facilitate analysis of new isolates. When incorporated with patient epidemiological data, the findings identified limited outbreaks against a broader 3-year period of sporadic external entry of many different strains and resistance vectors into the hospital. These findings highlight the utility of genomic analyses in internal and external surveillance efforts to stem the transmission of drug-resistant strains within and across health care institutions.ImportanceWe demonstrate how detection of resistance genes within mobile elements and resistance-carrying strains furthers active surveillance efforts for drug resistance. Whole-genome sequencing is increasingly available in hospital laboratories and provides a powerful and nuanced means to define the local landscape of drug resistance. In this study, isolates of Klebsiella pneumoniae and Enterobacter cloacae with resistance to carbapenem antibiotics were sequenced. Multiple carbapenemase genes were identified that resided in distinct transposons and plasmids. This mobilome, or population of mobile elements capable of mobilizing drug resistance, further highlighted the degree of strain heterogeneity while providing a detailed timeline of carbapenemase entry into the hospital over a 3-year period. These surveillance efforts support effective targeting of infection control resources and the development of institution-specific repositories of resistance genes and the mobile elements that carry them.

Project description:PurposeCarbapenem-resistant Enterobacteriaceae (CRE) infection has become a concerning threat, especially in hospital settings; however, its phenotypic characterization, association with rectal colonization and subsequent bloodstream infections (BSI) remain to be clarified. This study aimed to investigate the incidence and risk factors of CRE infection in rectal CRE carriers and to understand the clonality of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains and their association with subsequent BSI in these patients.Patients and methodsThis was a prospectively designed cohort study. Hospitalized patients treated at our institution from April 2019 to October 2020 with intestinal CRE carriage were screened at admission and weekly thereafter until death or discharge from the hospital. Stool and blood samples were obtained for strain growth and mass spectrometry. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRE. The clonality of the CRE strains and their corresponding clinical infection strains was studied by whole-genome sequencing to explore the mechanism of drug resistance and evaluate possible transmission. CRE-associated risk factors were analyzed in combination with epidemiological data.ResultsOf the 1203 patients, 85 were colonized by CRE and 21 developed CRE infection, of whom 13 developed CRE bloodstream infection (BSI). Ninety-one CRE strains were isolated from the rectal specimens of the 85 patients. Tracheotomy and chemotherapy in the past three months were independent risk factors for CRE infection in intestinal CRE carriers. ST11-KL64 (92.3%, 24/26) was the most dominant capsule and multilocus sequence typing (MLST) type among clonal CRKP isolates. Single-nucleotide polymorphism clustering showed homology of representative colonization and infection CRKP strain pairs (n=13) in the same patient. One group of leading clones was endemic in surgical intensive care units (ICUs). Twenty-four CRKP strains carried β-lactamase K. pneumonia carbapenemase 2, and 73.1% (19 strains) of CRKP carried mucoid phenotype regulator genes A2 and iucABCD.ConclusionIn summary, intestinal CRE colonization was detectable at an elevated rate among hospitalized patients and prevalent in ICU patients, with potential rapid horizontal transmission, providing evidence that CRE BSI infection in hospitalized patients might be due to their colonized strains and indicates the correlation between intestinal colonization and BSI.

Dataset Information

A mathematical model and inference method for bacterial colonization in hospital units applied to active surveillance data for carbapenem-resistant enterobacteriaceae.

Publications

A mathematical model and inference method for bacterial colonization in hospital units applied to active surveillance data for carbapenem-resistant enterobacteriaceae.

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