Dataset Information

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

ABSTRACT: Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were bla _NDM (42.8%), bla _KPC (38.4%), and bla _OXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P?Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (bla _NDM and bla _KPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P?=?0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P?=?0.003), and hospitalization in the preceding 1?year (aOR, 1.42; 95% CI, 1.01 to 2.02; P?=?0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.

SUBMITTER: Marimuthu K

PROVIDER: S-EPMC6761519 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Marimuthu Kalisvar K Ng Oon Tek OT Cherng Benjamin Pei Zhi BPZ Fong Raymond Kok Choon RKC Pada Surinder Kaur SK De Partha Pratim PP Ooi Say Tat ST Smitasin Nares N Thoon Koh Cheng KC Krishnan Prabha Unny PU Ang Michelle Lay Teng MLT Chan Douglas Su Gin DSG Kwa Andrea Lay Hoon ALH Deepak Rama Narayana RN Chan Yu Kit YK Chan Yvonne Fu Zi YFZ Huan Xiaowei X Zaw Linn Kyaw K Tee Nancy Wen Sim NWS Tan Thean Yen TY Koh Tse Hsien TH Lin Raymond Tzer Pin RTP Hsu Li Yang LY Sengupta Sharmila S Paterson David L DL Perencevich Eli E Harbarth Stephan S Teo Jeanette J Venkatachalam Indumathi I

Antimicrobial agents and chemotherapy 20190923 10

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with C ...[more]

PMID: 31383670

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Project description:Carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) are highly drug-resistant Gram-negative bacteria. They include New Delhi metallo-ß-lactamase (NDM)-producing carbapenemase (50.4% of all species in Ontario). Antibiotic challenges for resistant bacteria in neonates pose challenges of unknown dosing and side effects. We report two antenatally diagnosed CP-CRE colonization scenarios with the NDM 1 gene. The case involves extreme preterm twins who had worsening respiratory distress at birth requiring ventilator support, with the first twin also having cardiovascular instability. They were screened for CP-CRE, and a polymyxin antibiotic commenced. In the delivery room, neonatal intensive care unit (NICU) and the follow-up clinic, in collaboration with the interdisciplinary group, contact precautions and isolation procedures were instituted. None of the infants exhibited infection with CP-CRE. Consolidating knowledge with regard to CP-CRE and modifying human behavior associated with its spread can mitigate potential negative consequences. This relates to now and later, when travel and prolific human to human contact resumes, from endemic countries, after the current COVID-19 pandemic. Standardized efforts to curb the acquisition of this infection would be judicious given the challenges of treatment and continued emerging antibiotic resistance. Simple infection control measures involving contact precautions, staff education and parental cohorting can be useful and cost-effective in preventing transmission. Attention to NICU specific measures, including screening of at-risk mothers (invitro fertilization conception) and their probands, careful handling of breastmilk, judicious antibiotic choice and duration of treatment, is warranted. What does this study add? CP-CRE is a nosocomial infection with increasing incidence globally, and a serious threat to public health, making it likely that these cases will present with greater frequency to the NICU team. Only a few similar cases have been reported in the neonatal literature. Current published guidelines provide a framework for general hospital management. Still, they are not specific to the NICU experience and the need to manage the parents' exposure and the infants. This article provides a holistic framework for managing confirmed or suspected cases of CP-CRE from the antenatal care through the NICU and into the follow-up clinic targeted at preventing or containing the spread of CP-CRE.

Project description:Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and that 95% of the CRE isolates were IMP-type carbapenemase producers. Here, the mechanisms for this regional dissemination of a single carbapenemase gene were investigated. Since the dissemination of CRE is primarily due to the transmission of carbapenemase genes located on plasmids, we analyzed the plasmidome of 230 CRE isolates carrying blaIMP by whole-genome sequencing and Southern blotting. blaIMP-6 was found to be predominantly disseminated among chromosomally distinct isolates through the pKPI-6 plasmid. Underlying the vast clonal dissemination of pKPI-6, various subpopulations deriving from pKPI-6 were identified, which had acquired advantages for the dissemination of CRE isolates. A cluster exhibiting heteroresistance against meropenem by the transcriptional regulation of blaIMP-6 caused an outbreak likely through covert transmission of blaIMP-6 For stable carriage of blaIMP-6, they occasionally integrated blaIMP-6 on their chromosomes. In addition, we detected one isolate that broadened the range of antimicrobial resistance through a single point mutation in blaIMP-6 on pKPI-6. Multifaceted analysis of the plasmidome granted us more accurate perspectives on the horizontal spread of CRE isolates, which is difficult to trace only by comparing the whole genomes. This study revealed the predominant spread of a specific carbapenemase-encoding plasmid accompanying the emergence of phenotypically diverse derivatives, which may facilitate further dissemination of CRE in various environments.IMPORTANCE Global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens human health by limiting the efficacy of antibiotics even against common bacterial infections. Carbapenem resistance, mainly due to carbapenemase, is generally encoded on plasmids and is spread across bacterial species by conjugation. Most CRE epidemiological studies have analyzed whole genomes or only contigs of CRE isolates. Here, plasmidome analysis on 230 CRE isolates carrying blaIMP was performed to shed light into the dissemination of a single carbapenemase gene in Osaka, Japan. The predominant dissemination of blaIMP-6 by the pKPI-6 plasmid among genetically distinct isolates was revealed, as well as the emergences of pKPI-6 derivatives that acquired advantages for further disseminations. Underlying vast clonal dissemination of a carbapenemase-encoding plasmid, heteroresistance was found in CRE offspring, which was generated by the transcriptional regulation of blaIMP-6, stabilization of blaIMP-6 through chromosomal integration, or broadened antimicrobial resistance due to a single point mutation in blaIMP-6.

Dataset Information

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Publications

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Similar Datasets

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