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Randomized Controlled Trial
. 2017 Nov;43(11):1613-1625.
doi: 10.1007/s00134-017-4766-4. Epub 2017 Apr 3.

Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial

Emmanuelle Cambau  1   2 , Isabelle Durand-Zaleski  3   4 , Stéphane Bretagne  5   6   7   8 , Christian Brun-Buisson  9 , Catherine Cordonnier  10 , Xavier Duval  11 , Stéphanie Herwegh  12 , Julien Pottecher  13 , René Courcol  12 , Sylvie Bastuji-Garin  14   15   16 ; EVAMICA study team
Collaborators, Affiliations
Randomized Controlled Trial

Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial

Emmanuelle Cambau et al. Intensive Care Med. 2017 Nov.

Abstract

Purpose: Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE).

Methods: Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCycler®SeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE).

Results: A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43-2.50; P < 0.001], with an absolute increase of 14.5% (95% CI 8.4-20.7). A trend towards an association was observed for SIE [35.4% (17/48) vs. 9.5% (2/21); OR 6.22 (0.98-39.6)], but not for FN [32.1% (70/218) vs. 30.2% (67/222), P = 0.66]. Overall, turn-around time was shorter during IP than during CP (22.9 vs. 49.5 h, P < 0.001) and hospital costs were similar (median, mean ± SD: IP €14,826, €18,118 ± 17,775; CP €17,828, €18,653 ± 15,966). Bootstrap analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients.

Conclusion: Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES. ClinicalTrials.gov registration number: NCT00709358.

Keywords: Aetiological source; Bacteremia; PCR; Sepsis.

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Conflict of interest statement

Conflicts of interest

The authors have no conflict of interest within the scope of this study.

Funding

The study was fund by the French Ministry of Health (Grant n°STIC IC0703; P070308 and IDRCB 2007-A01443-50). Clinical research was monitored by the Assistance Publique-Hôpitaux de Paris (AP-HP) institution and particularly the Unité de Recherche Clinique (URC) Mondor. Data basis was collected and stored at URC Mondor. The trial protocol was approved by the institutional ethics committee of Ile-de-France (CPP Ile de France 1 no. 0811715). Written informed consents were obtained for all patients and good practices in clinical research were monitored by the Assistance Publique-Hôpitaux de Paris (AP-HP) institution.

Figures

Fig. 1
Fig. 1
Flowchart of the patients according to the intervention and control periods and with regard to type of infection
Fig. 2
Fig. 2
Venn diagram presenting the microbial diagnosis given by blood cultures (BC) and the molecular test (LSF) for patients during the intervention period. GNB Gram-negative bacilli (enterobacteria, acinetobacter and pseudomonades), GPC Gram-positive cocci (staphylococci, streptococci and enterococci), blue circle BC positive cases, green circle positive molecular test. Cases could be diagnosed with more than one pathogen
Fig. 3
Fig. 3
Incremental cost and effectiveness of the molecular test when compared to standard workup: cost effectiveness plane for incremental costs and difference in 24-h documentation for neutropenic patients and patients with severe sepsis
See this image and copyright information in PMC

Comment in

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