Abstract

BackgroundCarbapenemase-producing enterobacteriaceae (CPE) are a major threat for severely ill patients. However, only limited data on the epidemiology and on evidence-based infection prevention and control measures are available. The aim of this study was to investigate the epidemiology of patients with CPE, characterizing the CPE isolates by their resistance mechanisms and genetic similarity, to explore risk factors for their acquisition, and to evaluate the effectiveness of the current CPE infection control measures.MethodsA retrospective case-control study was performed using data from 2011 to 2016 in a 1800-bed academic hospital in Central Europe, where risk-based screening at patients´ admission is performed. Carbapenem resistance mechanisms of all carbapenem resistant enterobacteriaceae from patients admitted during this period were investigated. Clinical data of the CPE-positive patients were analysed and compared to a matched control group (case-control ratio of 1:3). We performed univariate and multivariate statistical analysis to identify risk factors for CPE acquisition.ResultsOf 621,623 admitted patients in the study period, 75 patients with carriage of carbapenem resistant enterobacteriaceae were included (0.12/1000 admittances). Carbapenemase-encoding genes were detected in 77.3% (58/75) of patients with carbapenem-resistant enterobacteriaceae. The enzyme blaOXA-48 was found in 34.5% (20/58), blaKPC in 29.3% (17/58), blaNDM enzymes in 20.7% (12/58) and blaVIM in 8.6% (5/58) of the isolates. The overall mortality among CPE patients was 25.9% (15/58) and attributable mortality of CPE was 53.3% (8/15). Multivariate analysis revealed four risk factors to be independent predictors of CPE carriage: the length of hospital admission > 20 days (AOR: 4.9, 95% CI: 1.4–15.5; P < 0.001), hospital admission within the previous year (AOR: 22.3, 95% CI: 3.9–88.4; P < 0.001), exposure to a healthcare facility in a country with high or unknown carbapenem-resistant enterobacteriaceae prevalence 3 months before admission (AOR: 11.8, 95% CI: 2.2–63.2; P < 0.01) and the use of antibiotics longer than 10 days (AOR: 5.2, 95% CI: 1.4–35.9; P < 0.05). The current risk-based screening strategy at hospital admission could not identify 37 (63.8%) of the 58 CPE-positive patients. Epidemiological investigation and genotyping revealed that no outbreaks due to CPE occurred during this period.ConclusionOverall, the CPE carriage rate in patients was very low, the attributable mortality, however, is alarming (53%). BlaOXA-48 and blaKPC were the main cause of carbapenem resistance in enterobacteriaceae. Although the strict application of standard infection control measures was effective for prevention of outbreaks in this setting, an enlarged risk based targeted screening strategy has to be implemented.

Highlights

  • Carbapenem-resistant enterobacteriaceae have recently been listed by the World Health Organisation (WHO) as antibiotic-resistant priority pathogens [1]

  • The aims of this study were to investigate the presence of carbapenemases in all carbapenem-resistant enterobacteriaceae isolated in the years 2011–2016, to identify carbapenemases using molecular methods, to identify risk factors for the presence of Carbapenemase-producing enterobacteriaceae (CPE) and to evaluate if current infection control measures are effective in both detection and containment of CPE

  • Carbapenem resistance and characterization of carbapenemases The presence of carbapenemases was identified in 77.3% (58/75) of carbapenem-resistant enterobacteriaceae

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Summary

Introduction

Carbapenem-resistant enterobacteriaceae have recently been listed by the World Health Organisation (WHO) as antibiotic-resistant priority pathogens [1]. Infections with carbapenem-resistant enterobacteriaceae are difficult to treat and may cause death in up to 50% of infected patients [2]. The major mechanism for carbapenem resistance in enterobacteriaceae is the production of enzymes of the class carbapenemases. Carbapenemaseproducing enterobacteriaceae are multidrug-resistant, because they harbour genes encoding for resistance against other antibiotic classes, such as fluoroquinolones and aminoglycosides [2]. Only limited data on the epidemiology and on evidence-based infection prevention and control measures are available. The aim of this study was to investigate the epidemiology of patients with CPE, characterizing the CPE isolates by their resistance mechanisms and genetic similarity, to explore risk factors for their acquisition, and to evaluate the effectiveness of the current CPE infection control measures

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