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Multicenter Study of the Risk Factors for Colonization or Infection with Carbapenem-Resistant Enterobacteriaceae in Children.

ABSTRACT: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly identified in children in the United States, but data on the epidemiology of CRE in this population are limited. The objectives of this study were to characterize the risk factors for colonization or infection with CRE and describe the microbiologic characteristics of pediatric CRE isolates. We performed a multicenter matched case-control study from January 2011 to October 2015 at three tertiary care pediatric centers. Case patients were hospitalized children with CRE isolated from clinical cultures and were matched in a 2:1 ratio to control patients with carbapenem-susceptible Enterobacteriaceae (CSE). Risk factors for colonization or infection with CRE were then evaluated using a multivariable conditional logistic regression. Additionally, we comprehensively reported the antimicrobial susceptibility pattern for CRE isolates. Sixty-three case patients were identified and matched to 126 control patients. On multivariable analysis, antipseudomonal antibiotic exposure within the previous 3 months (odds ratio [OR], 5.20; 95% confidence interval [CI], 1.71 to 15.9; P = 0.004), prior surgery (OR, 6.30; 95% CI, 1.83 to 21.6; P = 0.003), and mechanical ventilation (OR, 12.4; 95% CI, 1.26 to 122; P = 0.031) were identified as risk factors for colonization or infection with CRE. Pediatric CRE isolates demonstrated relatively low rates of resistance to amikacin (5%) and ciprofloxacin (25%). Our findings support an important role for antibiotic stewardship interventions limiting the unnecessary use of antipseudomonal antibiotics as a strategy to prevent widespread emergence of CRE in children. Future studies should further characterize molecular determinants of antibiotic resistance among pediatric CRE isolates.

SUBMITTER: Chiotos K

PROVIDER: S-EPMC5700345 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Multicenter Study of the Risk Factors for Colonization or Infection with Carbapenem-Resistant Enterobacteriaceae in Children.

Chiotos Kathleen K Tamma Pranita D PD Flett Kelly B KB Naumann Matthew M Karandikar Manjiree V MV Bilker Warren B WB Zaoutis Theoklis T Han Jennifer H JH

Antimicrobial agents and chemotherapy 20171122 12

Carbapenem-resistant <i>Enterobacteriaceae</i> (CRE) are increasingly identified in children in the United States, but data on the epidemiology of CRE in this population are limited. The objectives of this study were to characterize the risk factors for colonization or infection with CRE and describe the microbiologic characteristics of pediatric CRE isolates. We performed a multicenter matched case-control study from January 2011 to October 2015 at three tertiary care pediatric centers. Case pa ...[more]

PMID: 28971864

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Project description:BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent public health threat. Intestinal colonization with CRE has been identified as a risk factor for the development of systemic CRE infection, but has not been compared to colonization with third and/or fourth generation cephalosporin-resistant (Ceph-R) Enterobacteriaceae. Moreover, the risk conferred by colonization on adverse outcomes is less clear, particularly in critically ill patients admitted to the intensive care unit (ICU).MethodsWe carried out a cohort study of consecutive adult patients screened for rectal colonization with CRE or Ceph-R upon ICU entry between April and July 2013. We identified clinical variables and assessed the relationship between CRE or Ceph-R colonization and subsequent systemic CRE infection within 30 days (primary outcome) and all-cause mortality within 90 days (secondary outcome).ResultsAmong 338 ICU patients, 94 (28%) were colonized with either Ceph-R or CRE. 26 patients developed CRE infection within 30 days of swab collection; 47% (N = 17/36) of CRE-colonized and 3% (N = 2/58) of Ceph-R colonized patients. 36% (N = 13/36) of CRE-colonized patients died within 90 days compared to 31% (N = 18/58) of Ceph-R-colonized and 15% (N = 37/244) of non-colonized patients. In a multivariable analysis, CRE colonization independently predicted development of a systemic CRE infection at 30 days (aOR 10.8, 95% CI2.8-41.9, p = 0.0006); Ceph-R colonization did not (aOR 0.5, 95% CI0.1-3.3, p = 0.5). CRE colonization was associated with increased 90-day mortality in a univariable analysis (p-value 0.001), in a multivariable model, previous hospitalization and medical ICU admission were independent predictors of 90-day mortality whereas CRE colonization approached significance (aOR 2.3, 95% CI1.0-5.3, p = 0.056).ConclusionsOur study highlights the increased risk of CRE infection and mortality in patients with CRE colonization at the time of ICU admission. Future studies are needed to assess how CRE colonization can guide empiric antibiotic choices and to develop novel decolonization strategies.

Project description:BACKGROUND: Increasing prevalence of ertapenem-resistant, carbapenem-susceptible Enterobacteriaceae (ERE) in Singapore presents a major therapeutic problem. Our objective was to determine risk factors associated with the acquisition of ERE in hospitalized patients; to assess associated patient outcomes; and to describe the molecular characteristics of ERE. METHODS: A retrospective case-case-control study was conducted in 2009 at a tertiary care hospital. Hospitalized patients with ERE and those with ertapenem-sensitive Enterobacteriaceae (ESE) were compared with a common control group consisting of patients with no prior gram-negative infections. Risk factors analyzed included demographics; co-morbidities; instrumentation and antibiotic exposures. Two parallel multivariate logistic regression models were performed to identify independent variables associated with ERE and ESE acquisition respectively. Clinical outcomes were compared between ERE and ESE patients. RESULTS: Twenty-nine ERE cases, 29 ESE cases and 87 controls were analyzed. Multivariate logistic regression showed that previous hospitalization (Odds ratio [OR], 10.40; 95% confidence interval [CI], 2.19-49.20) and duration of fluoroquinolones exposure (OR, 1.18 per day increase; 95% CI, 1.05-1.34) were unique independent predictors for acquiring ERE. Duration of 4(th)-generation cephalosporin exposure was found to predict for ESE acquisition (OR, 1.63 per day increase; 95% CI, 1.05-2.54). In-hospital mortality rates and clinical response rates were significantly different between ERE and ESE groups, however ERE infection was not a predictor of mortality. ERE isolates were clonally distinct. Ertapenem resistance was likely to be mediated by the presence of extended-spectrum β-lactamases or plasmid-borne AmpC in combination with impermeability due to porin loss and/or efflux pumps. CONCLUSION: Prior hospitalization and duration of fluoroquinolone treatment were predictors of ERE acquisition. ERE infections were associated with higher mortality rates and poorer clinical response rates when compared to ESE infections.

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

Multicenter Study of the Risk Factors for Colonization or Infection with Carbapenem-Resistant Enterobacteriaceae in Children.

Publications

Multicenter Study of the Risk Factors for Colonization or Infection with Carbapenem-Resistant Enterobacteriaceae in Children.

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