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 (1, 11) , Stéphanie Herwegh (12) , Julien Pottecher (13) , René Courcol (12) , Sylvie Bastuji-Garin (14, 3, 15, 16) , The Evamica Study Team

1 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
2 Hôpital Lariboisière
3 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
4 Unité de Recherche Clinique en Economie de la santé d'Ile de France (URC Eco)
5 Service de parasitologie [Mondor]
6 UPD7 - Université Paris Diderot - Paris 7
7 Mycologie moléculaire - Molecular Mycology
8 AP-HP - Hopital Saint-Louis [AP-HP]
9 Service de réanimation médicale
10 Service d'hématologie clinique
11 CIC - CHU Bichat
12 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
13 Les Hôpitaux Universitaires de Strasbourg (HUS)
14 Hôpital Henri Mondor
15 CEpiA - Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique
16 IMRB - Institut Mondor de Recherche Biomédicale

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

Domains: Mycology

Emmanuelle Cambau, Isabelle Durand-Zaleski, Stéphane Bretagne, Christian Brun-Buisson, Catherine Cordonnier, et al.. Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial. Intensive Care Medicine, 2017, 43 (11), pp.1613 - 1625. ⟨10.1007/s00134-017-4766-4⟩. ⟨pasteur-01854026⟩