title: Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: APHP-Lariboisière, Bacteriology Laboratory, 75010, Paris, France. emmanuelle.cambau@aphp.fr.|Univ Paris Diderot, Sorbonne Paris Cité, INSERM, UMR1137 IAME, 75018, Paris, France. emmanuelle.cambau@aphp.fr.
authors.forename: Emmanuelle
authors.identifier: http://orcid.org/0000-0001-5944-2530
authors.initials: E
authors.lastname: Cambau
authors.affiliation: APHP-URC ECO, Créteil, France.|Université Paris Est, UFR de Médecine, 94010, Créteil, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durand-Zaleski
authors.affiliation: APHP-Henri Mondor, Parasitology and Mycology Laboratory, 94010, Créteil, France.|APHP-Saint Louis, Parasitology and Mycology Laboratory, 75010, Paris, France.|Sorbonne Paris Cité, University Paris Diderot, Paris, France.|Molecular Mycology Unit, Institut Pasteur, National Reference Center of Invasive Mycoses and Antifungals, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bretagne
authors.affiliation: APHP- Henri Mondor, Intensive Care Department, 94010, Créteil, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Brun-Buisson
authors.affiliation: APHP- Henri Mondor, Haematology Department and University Paris-Est Créteil, 94010, Créteil, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cordonnier
authors.affiliation: APHP-Bichat, Centre d'investigation Clinique CIC 1425, INSERM UMR 1137 IAME, University Paris Diderot, 75018, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Duval
authors.affiliation: CHU Lille, Microbiology Institute, 59000, Lille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Herwegh
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Service d'Anesthésie-Réanimation chirurgicale, Université de Strasbourg, FMTS, EA 3072, 67098, Strasbourg, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pottecher
authors.affiliation: CHU Lille, Microbiology Institute, 59000, Lille, France.
authors.forename: René
authors.initials: R
authors.lastname: Courcol
authors.affiliation: APHP-Henri Mondor, Public Health Department, 94010, Créteil, France.|University Paris Est (UPE), IMRB, CEpiA (Clinical Epidemiology and Ageing Unit, EA7376), 94010, Créteil, France.|APHP, Henri Mondor Hospital, Clinical Research Unit (URC Mondor), 94010, Créteil, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bastuji-Garin
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D018592:Cross-Over Studies; D004696:Endocarditis / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D064147:Febrile Neutropenia / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000191:economics*; D058996:Quality Improvement; D012189:Retrospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D013997:Time Factors; D061665:Time-to-Treatment / Q000191:economics
chemical_list: D000900:Anti-Bacterial Agents
keywords: Aetiological source; Bacteremia; PCR; Sepsis