Project

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An interventional study to evaluate the impact of a rapid screening strategy in improving nosocomial ESBL and CPE control in critically ill patients

Applicant Harbarth Stephan Jürgen
Number 177454
Funding scheme NRP 72 Antimicrobial Resistance
Research institution Infection Control Program Hôpitaux Universitaires de Genève Faculté de Médecine, Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Infectious Diseases
Start/End 01.03.2018 - 31.10.2021
Approved amount 320'000.00
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Keywords (5)

CPE; Infection control; ESBL; Clinical trial; Test diagnostique rapide

Lay Summary (French)

Lead
Les Entérobactéries productrices de BLSE et/ou de Carbapénémases sont un problème de santé publique majeur entrainant des coûts humains et économiques dans le secteur hospitalier. Les méthodes diagnostiques existantes dans le contexte d’une stratégie de dépistage sont capitales pour prévenir leur transmission mais ralentissent toute prise en charge adéquate. Malgré la commercialisation d’un test diagnostique rapide et efficace développé afin de les remplacer, de nombreuses questions se posent sur son utilité clinique. Ce projet de recherche vise à répondre à ces questions.
Lay summary

Contenu et objectifs du travail de recherche

Les Entérobactéries productrices de BLSE (E-BLSE) et/ou de Carbapénémases (CPE) sont un problème de santé publique majeur, entraînant une prolongation du séjour hospitalier et une augmentation de la mortalité dans les hôpitaux. De ce fait, une stratégie de dépistage sensible et rapide est nécessaire pour contenir les transmissions et prévenir des complications. Cependant les seuls moyens diagnostiques utilisés pour dépister les E-BLSE et CPE reposent sur des cultures bactériennes, retardant toute prise en charge adéquate d’au moins 48 heures et ne permettant pas l’identification précise de la résistance. Afin de répondre à ce besoin, des tests plus précis (génotypiques) tels que le « Loop-Mediated Isothermal Amplification (LAMP)» sont développés, mais jusqu’à présent leur pertinence clinique et économique n’a pas été évaluée dans un contexte hospitalier pour le dépistage en routine des E-BLSE et CPE.

Ce projet cherche à comparer l’efficacité clinique et économique du dépistage en routine pour les E-BLSE et CPE aux soins intensifs, sur la base i) des moyens diagnostiques existants, et ii) d’une  nouvelle stratégie de dépistage comportant le test diagnostique « LAMP ». Cette stratégie de dépistage sera également évaluée dans le contexte d’une récente recommandation institutionnelle négligeant une bactérie productrice de BLSE (Escherichia coli), à l’exception d’un de ses sous-types également détecté par cette nouvelle stratégie de dépistage.

Contexte scientifique et social du projet de recherche

Cette étude est un projet de recherche clinique mené dans le cadre du contrôle des infections nosocomiales, de la microbiologie et des soins intensifs. Cette recherche est nécessaire pour évaluer non seulement la pertinence clinique et économique d’un nouveau test diagnostique dans un milieu hospitalier, mais également la validité des dernières évidences présentes dans le contrôle des infections. Cette nouvelle stratégie entrainera au final un dépistage précoce des porteurs de résistances (E-BLSE et CPE), une meilleure gestion des épidémies dues à ces résistances et une prise en charge de meilleure qualité. 

Direct link to Lay Summary Last update: 18.12.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroconversion and occupational exposure of employees at a Swiss university hospital: A large longitudinal cohort study
Martischang Romain, Iten Anne, Arm Isabelle, Abbas Mohamed, Meyer Benjamin, Yerly Sabine, Eckerle Isabella, Pralong Jacques, Sauser Julien, Suard Jean-Claude, Kaiser Laurent, Pittet Didier, Harbarth Stephan (2021), Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroconversion and occupational exposure of employees at a Swiss university hospital: A large longitudinal cohort study, in Infection Control & Hospital Epidemiology, 1-8.
Household carriage and acquisition of extended-spectrum β-lactamase–producing Enterobacteriaceae: A systematic review
Martischang Romain, Riccio Maria E., Abbas Mohamed, Stewardson Andrew J., Kluytmans Jan A. J. W., Harbarth Stephan (2020), Household carriage and acquisition of extended-spectrum β-lactamase–producing Enterobacteriaceae: A systematic review, in Infection Control & Hospital Epidemiology, 41(3), 286-294.
Nation-wide survey of screening practices to detect carriers of multi-drug resistant organisms upon admission to Swiss healthcare institutions
Martischang Romain, Buetti Niccolo, Balmelli Carlo, Saam Mirko, Widmer Andreas, Harbarth Stephan (2019), Nation-wide survey of screening practices to detect carriers of multi-drug resistant organisms upon admission to Swiss healthcare institutions, in Antimicrobial Resistance & Infection Control, 8(1), 37-37.
Screening for Intestinal Carriage of Extended-spectrum Beta-lactamase–producing Enterobacteriaceae in Critically Ill Patients: Expected Benefits and Evidence-based Controversies
Zahar Jean-Ralph, Blot Stijn, Nordmann Patrice, Martischang Romain, Timsit Jean-François, Harbarth Stephan, Barbier François (2019), Screening for Intestinal Carriage of Extended-spectrum Beta-lactamase–producing Enterobacteriaceae in Critically Ill Patients: Expected Benefits and Evidence-based Controversies, in Clinical Infectious Diseases, 68(12), 2125-2130.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ICPIC 2019 Talk given at a conference AN INTERVENTIONAL STUDY TO EVALUATE THE IMPACT OF A RAPID SCREENING STRATEGY IN IMPROVING NOSOCOMIAL ESBL AND CPE CONTROL IN CRITICALLY ILL PATIENTS 15.09.2021 Geneve, Switzerland Martischang Romain; Fankhauser Carolina Maria; Harbarth Stephan Jürgen;
IDWeek2019 Talk given at a conference poster 01.10.2019 Washington DC, United States of America Martischang Romain;


Abstract

Colonization with antimicrobial-resistant pathogens such as extended-spectrum beta-lactamase-producing enterobacteriacae (ESBL-PE) or carbapenemase-producing enterobacteriacae (CPE) places patients at high risk of antibiotic-resistant nosocomial infection. Early and rapid identification of critically ill patients colonized with ESBL-PE/CPE, and subsequent prevention of patient-to-patient spread of ESBL-PE/CPE through proper infection control are potentially useful interventions to control ESBL-PE/CPE cross-infection in the intensive care unit (ICU). Thus, targeted ESBL-PE/CPE screening on admission may help to identify unknown ESBL carriers, prevent transmission and could help to reduce time to adequate treatment in case of ESBL-PE/CPE infection. However, current microbiologic screening methods to detect previously unknown ESBL-PE/CPE carriers are slow. This delay impacts the discontinuation of pre-emptive isolation measures among patients at high risk of ESBL-PE/CPE carriage and may increase healthcare costs and preventable adverse events. To further complicate matters, there is ongoing controversy whether carriers of ESBL-producing E.coli require contact precautions, in contrast to other ESBL-PE, such as Klebsiella spp and Enterobacter spp.There is an ongoing need for a fast, reliable and inexpensive diagnostic screening method for ESBL-PE and CPE strains of major concern in Switzerland, which may also include the capacity to identify transmissible and virulent ESBL-E.coli clones requiring contact precautions in the ICU setting. A novel strategy with 2 rapid diagnostic methods could allow individualizing and speeding up the implementation of appropriate infection control measures, or discontinue preemptive isolation as fast as possible. First, the loop-mediated isothermal amplification reaction (LAMP) is an isothermal molecular amplification method already developed and previously validated in our institution. Compared to conventional PCRs for the detection of the predominant ESBL-PE and CPE types, this new technique is faster and potentially more cost-beneficial, but with a similar diagnostic accuracy. Second, we have recently developed a specific molecular test able to detect the virulent and transmissible ESBL-E. coli strain ST131 H30 in order to tailor the implementation of preventive measures to this specific E.coli clone.This study aims to evaluate the effectiveness of an innovative screening strategy based on 2 rapid tests to improve the implementation or discontinuation of ESBL-PE/CPE control measures among critically ill patients, including also a specific test to risk-stratify ESBL-producing E. coli in order to discriminate epidemic clones (ST131 H30) requiring contact precautions. We will test the specific hypotheses that a screening program with a novel diagnostic strategy enabling early detection of ESBL-PE and CPE carriage in 2 ICUs at HUG can:1.Decrease unnecessary isolation-days for patients suspected to be colonized with ESBL-PE and CPE, but who are finally screening-negative;2.Decrease the time between patient screening and contact isolation of previously unknown ESBL-PE and CPE carriers in this high-risk setting;3.Decrease the risk of nosocomial cross-transmission of ESBL-PE;4.Reduce unnecessary costs from an institutional perspective and provide a cost-effective screening option.To test these hypotheses, we propose a a quasi-experimental, prospective, cross-over cohort study conducted over 3 years (2018-2020) to compare a rapid ESBL-PE/CPE screening strategy with the currently used routine diagnostic method. Patients will be screened by rectal swabs on admission (targeted screening of high-risk patients) and once weekly (universal screening) in 2 mixed medico-surgical ICUs with a total of 36 beds and current ESBL-PE prevalence of 10%. During the first interventional phase in 2019 (6 months), one ICU will implement (or discontinue) contact precautions according to the standard microbiologic method while the other ward will use the novel diagnostic strategy. The protocol will be switched between these two ICUs during the second phase (6 months), after a wash-out period of 2 months. During both phases, routine tests will be continued in parallel to the novel diagnostic strategy. Statistical analysis will be performed in the 3rd year of the study (2020). Time (h) to notification and implementation (or discontinuation) of isolation measures will be measured as primary endpoints, stratified by diagnostic method (novel strategy vs. current method). As secondary outcome, transmission events will be analyzed through weekly prevalence surveys and a cost-effectiveness study will compare the benefit of spared isolation days and the cost of diagnostic tests.Overall, this proposal allows application of a novel rapid diagnostic strategy to detect ESBL-PE/CPE colonization and improve patient safety by rapid identification and isolation of ICU patients carrying these multi-resistant bacteria. It will also allow earlier discontinuation of preemptive isolation in high-risk patients with negative screening results. Thus, this project will promote technological development with a direct impact on clinical care.
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