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, Isabelle Durand-Zaleski, Stéphane Bretagne, Christian Brun-Buisson, Catherine Cordonnier, Xavier Duval, Stéphanie Herwegh, Julien Pottecher, René Courcol, Sylvie Bastuji-Garin, EVAMICA study team, Agnès Lefort, Jean Mantz, Sébastien Pease, Leïla Lavagna, Marie Hélène Nicolas-Chanoine, Véronique Leflon, Estelle Marcon, Raymond Ruimy, Antoine Andremont, Jacques Lebras, Bernard Iung, Bernard Regnier, Patrick Yeni, Philippe Montravers, Bruno Mourvillier, Emila Ilic-Habensus, Nadia El Alami Talbi, Sigismond Lasocki, Didier Bouscary, Jean-Paul Mira, David Grimaldi, Nathalie Marin, Alexandra Doloy, Claire Poyart, Emmanuel Scherrer, Cecile Chambon-Pautas, Fabrice Cook, Armand Mekontso-Dessap, Frédérique Schortgen, Karine Chedevergne, Jean-Paul Vernant, Liliane Gauvin-Bodin, Jean-Louis Trouillet, Jean Chastre, François Bricaire, Florence Brossier, Vincent Jarlier, Nathalie Dheder, Ania Nieszkowska, Annick Datry, Arnaud Fekkar, Pierre Buffet, Rommy Mazier, Sophie Brun, Vanina Meyssonnier, Françoise Isnard, Jean-Luc Baudel, Jean-Luc Meynard, Jean-Claude Petit, Valérie Lalande, Patricia Roux, Emmanuel Raffoux, Patricia Ribaud, Vincent Das, Benoit Schlemmer, Elie Azoulay, Loic Chimot, Jean-Michel Molina, Diane Ponscarme, Juliette Pavie, François Simon, Isabelle Casin, Jean Menotti, Didier Gruson, Emilie Bessède, Emmanuelle Guilhon, Isabelle Accoceberry, Pascal Millet, Cécile Bébéar, Christian Berthoux, Jean-Marie Tonnelier, Michel Garre, Geneviève Hery-Arnaud, Christopher Payan, Gilles Nevez, Jean-Francois Timsit, Jean-Yves Cahn, Jean-Paul Brion, Bernard Le Beau, Stephane Courby, Hervé Pelloux, Max Maurin, Olivier Epaulard, Rebecca Hamidfar, Céline Berthon, Valérie Coiteux, Louis Terriou, Saadalla Nseir, Jean-Luc Auffray, Jean-Pierre Jouet, Alain Durocher, Karine Faure, Marc Clavel, Daniel Camus, Anthony Dugard, Chantal Tisseuil, Cécile Duchiron, Daniel Ajzenberg, Dominique Bordessoule, Fabien Garnier, Bruno François, Marie-Cécile Ploy, Marie-Laure Darde, Marie-Pierre Chaury, Stephane Giraud, Arnaud Jaccard, Stéphane Moreau, Liliane Réménieras, Mohamed Touati, Pascal Turlure, Jean-Bernard Amiel, Nicolas Pichon, Déborah Postil, Philippe Vignon, Daniel Espinouse, Didier Jacques, Frédérique De Monbrison, Jean-Michel Grozel, Monique Chomarat, Pierre-Yves Gueugniaud, Rokiatou Sanogo, Michel Drancourt, Pierre Edouard Fournier, Véronique Roux, Alain Delmer, Chantal Himberlin, Brigitte Kolb, Quoc Hung Lé, Morgane Appriou, Joël Cousson, Pierre Nazeyrollas, Christophe Strady, Christophe Dechamps, Véronique Vernet, Alain Delmer, Dominique Toubas, Denis Guyotat, Christian Auboyer, Fabrice Zeni, Eric Alamartine, Pascal Cathebras, Frédéric Lucht, Alain Viallon, Adrien Melis, Alain Ros, Anne Carricajo, Camille Devanlay, Carine Labruyere, Catherine Vautrin, Céline Cazorla, Emmanuelle Tavernier, Florence Grattard, Gérald Aubert, Jerome Morel, Jérome Cornillon, Karima Abba, Pierre Flori, Roger Tran Manh Sung, Bruno Pozzetto, Francis Schneider, Yves Hansmann, Raoul Herbrecht, Benoit Jaulhac, Yves Piémont, Valérie Lestcher, Philippe Colombat, Delphine Senecal, Denis Garot, Dominique Perrottin, Jean-Marc Besnier, Alain Goudeau, Philippe Lanotte, Jacques Chandenier, Samia Baloul, Céline Corbel, Moufida Dabbech, Mabel Gaba, Elsa Jozefowicz, Magali Lafaye, Fabien Maugard, Remi Rabeuf, Hasina Rabetrano, Kalaivani Veerabudun, Cédric Viallette, Jean-Paul Stahl, Laurence Delhaes, Emmanuelle Cambau, Isabelle Durand-Zaleski, Stéphane Bretagne, Christian Brun-Buisson, Catherine Cordonnier, Xavier Duval, Stéphanie Herwegh, Julien Pottecher, René Courcol, Sylvie Bastuji-Garin, EVAMICA study team, Agnès Lefort, Jean Mantz, Sébastien Pease, Leïla Lavagna, Marie Hélène Nicolas-Chanoine, Véronique Leflon, Estelle Marcon, Raymond Ruimy, Antoine Andremont, Jacques Lebras, Bernard Iung, Bernard Regnier, Patrick Yeni, Philippe Montravers, Bruno Mourvillier, Emila Ilic-Habensus, Nadia El Alami Talbi, Sigismond Lasocki, Didier Bouscary, Jean-Paul Mira, David Grimaldi, Nathalie Marin, Alexandra Doloy, Claire Poyart, Emmanuel Scherrer, Cecile Chambon-Pautas, Fabrice Cook, Armand Mekontso-Dessap, Frédérique Schortgen, Karine Chedevergne, Jean-Paul Vernant, Liliane Gauvin-Bodin, Jean-Louis Trouillet, Jean Chastre, François Bricaire, Florence Brossier, Vincent Jarlier, Nathalie Dheder, Ania Nieszkowska, Annick Datry, Arnaud Fekkar, Pierre Buffet, Rommy Mazier, Sophie Brun, Vanina Meyssonnier, Françoise Isnard, Jean-Luc Baudel, Jean-Luc Meynard, Jean-Claude Petit, Valérie Lalande, Patricia Roux, Emmanuel Raffoux, Patricia Ribaud, Vincent Das, Benoit Schlemmer, Elie Azoulay, Loic Chimot, Jean-Michel Molina, Diane Ponscarme, Juliette Pavie, François Simon, Isabelle Casin, Jean Menotti, Didier Gruson, Emilie Bessède, Emmanuelle Guilhon, Isabelle Accoceberry, Pascal Millet, Cécile Bébéar, Christian Berthoux, Jean-Marie Tonnelier, Michel Garre, Geneviève Hery-Arnaud, Christopher Payan, Gilles Nevez, Jean-Francois Timsit, Jean-Yves Cahn, Jean-Paul Brion, Bernard Le Beau, Stephane Courby, Hervé Pelloux, Max Maurin, Olivier Epaulard, Rebecca Hamidfar, Céline Berthon, Valérie Coiteux, Louis Terriou, Saadalla Nseir, Jean-Luc Auffray, Jean-Pierre Jouet, Alain Durocher, Karine Faure, Marc Clavel, Daniel Camus, Anthony Dugard, Chantal Tisseuil, Cécile Duchiron, Daniel Ajzenberg, Dominique Bordessoule, Fabien Garnier, Bruno François, Marie-Cécile Ploy, Marie-Laure Darde, Marie-Pierre Chaury, Stephane Giraud, Arnaud Jaccard, Stéphane Moreau, Liliane Réménieras, Mohamed Touati, Pascal Turlure, Jean-Bernard Amiel, Nicolas Pichon, Déborah Postil, Philippe Vignon, Daniel Espinouse, Didier Jacques, Frédérique De Monbrison, Jean-Michel Grozel, Monique Chomarat, Pierre-Yves Gueugniaud, Rokiatou Sanogo, Michel Drancourt, Pierre Edouard Fournier, Véronique Roux, Alain Delmer, Chantal Himberlin, Brigitte Kolb, Quoc Hung Lé, Morgane Appriou, Joël Cousson, Pierre Nazeyrollas, Christophe Strady, Christophe Dechamps, Véronique Vernet, Alain Delmer, Dominique Toubas, Denis Guyotat, Christian Auboyer, Fabrice Zeni, Eric Alamartine, Pascal Cathebras, Frédéric Lucht, Alain Viallon, Adrien Melis, Alain Ros, Anne Carricajo, Camille Devanlay, Carine Labruyere, Catherine Vautrin, Céline Cazorla, Emmanuelle Tavernier, Florence Grattard, Gérald Aubert, Jerome Morel, Jérome Cornillon, Karima Abba, Pierre Flori, Roger Tran Manh Sung, Bruno Pozzetto, Francis Schneider, Yves Hansmann, Raoul Herbrecht, Benoit Jaulhac, Yves Piémont, Valérie Lestcher, Philippe Colombat, Delphine Senecal, Denis Garot, Dominique Perrottin, Jean-Marc Besnier, Alain Goudeau, Philippe Lanotte, Jacques Chandenier, Samia Baloul, Céline Corbel, Moufida Dabbech, Mabel Gaba, Elsa Jozefowicz, Magali Lafaye, Fabien Maugard, Remi Rabeuf, Hasina Rabetrano, Kalaivani Veerabudun, Cédric Viallette, Jean-Paul Stahl, Laurence Delhaes

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.

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

References

    1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228. doi: 10.1007/s00134-012-2769-8.
    1. de Kraker ME, Jarlier V, Monen JC, Heuer OE, van de Sande N, Grundmann H. The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. Clin Microbiol Infect. 2013;19:860–868. doi: 10.1111/1469-0691.12028.
    1. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad, II, Rolston KV, Young JA, Wingard JR, Infectious Diseases Society of A Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:e56–e93. doi: 10.1093/cid/cir073.
    1. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG, Jr, Ryan T, Bashore T, Corey GR. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633–638. doi: 10.1086/313753.
    1. Duval X, Delahaye F, Alla F, Tattevin P, Obadia JF, Le Moing V, Doco-Lecompte T, Celard M, Poyart C, Strady C, Chirouze C, Bes M, Cambau E, Iung B, Selton-Suty C, Hoen B. Temporal trends in infective endocarditis in the context of prophylaxis guideline modifications: three successive population-based surveys. J Am Coll Cardiol. 2012;59:1968–1976. doi: 10.1016/j.jacc.2012.02.029.
    1. Shorr AF, Micek ST, Welch EC, Doherty JA, Reichley RM, Kollef MH. Inappropriate antibiotic therapy in Gram-negative sepsis increases hospital length of stay. Crit Care Med. 2011;39:46–51. doi: 10.1097/CCM.0b013e3181fa41a7.
    1. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–1596. doi: 10.1097/01.CCM.0000217961.75225.E9.
    1. Timsit JF, Citerio G, Bakker J, Bassetti M, Benoit D, Cecconi M, Curtis JR, Hernandez G, Herridge M, Jaber S, Joannidis M, Papazian L, Peters M, Singer P, Smith M, Soares M, Torres A, Vieillard-Baron A, Azoulay E. Year in review in Intensive Care Medicine 2013: III. Sepsis, infections, respiratory diseases, pediatrics. Intensive Care Med. 2014;40:471–483. doi: 10.1007/s00134-014-3235-6.
    1. Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis. 2014;14:13. doi: 10.1186/1471-2334-14-13.
    1. Brun-Buisson C, Meshaka P, Pinton P, Vallet B. EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 2004;30:580–588. doi: 10.1007/s00134-003-2121-4.
    1. Pautas C, Sbidian E, Hicheri Y, Bastuji-Garin S, Bretagne S, Corbel C, Gregoire L, Maury S, Merabet L, Cordonnier C, Cambau E. A new workflow for the microbiological diagnosis of febrile neutropenia in patients with a central venous catheter. J Antimicrob Chemother. 2012;68:943–946. doi: 10.1093/jac/dks462.
    1. Reinhart K, Bauer M, Riedemann NC, Hartog CS. New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev. 2012;25:609–634. doi: 10.1128/CMR.00016-12.
    1. Cordonnier C, Buzyn A, Leverger G, Herbrecht R, Hunault M, Leclercq R, Bastuji-Garin S. Epidemiology and risk factors for gram-positive coccal infections in neutropenia: toward a more targeted antibiotic strategy. Clin Infect Dis. 2003;36:149–158. doi: 10.1086/345435.
    1. Baron EJ, Miller JM, Weinstein MP, Richter SS, Gilligan PH, Thomson RB, Jr, Bourbeau P, Carroll KC, Kehl SC, Dunne WM, Robinson-Dunn B, Schwartzman JD, Chapin KC, Snyder JW, Forbes BA, Patel R, Rosenblatt JE, Pritt BS. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a) Clin Infect Dis. 2013;57:e22–e121. doi: 10.1093/cid/cit278.
    1. Tabah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi de Carvalho F, Paiva JA, Cakar N, Ma X, Eggimann P, Antonelli M, Bonten MJ, Csomos A, Krueger WA, Mikstacki A, Lipman J, Depuydt P, Vesin A, Garrouste-Orgeas M, Zahar JR, Blot S, Carlet J, Brun-Buisson C, Martin C, Rello J, Dimopoulos G, Timsit JF. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med. 2012;38:1930–1945. doi: 10.1007/s00134-012-2695-9.
    1. See I, Freifeld AG, Magill SS. causative organisms and associated antimicrobial resistance in healthcare-associated, central line-associated bloodstream infections from oncology settings, 2009–2012. Clin Infect Dis. 2016;62:1203–1209. doi: 10.1093/cid/ciw113.
    1. Madaras-Kelly K, Jones M, Remington R, Caplinger C, Huttner B, Samore M. Description and validation of a spectrum score method to measure antimicrobial de-escalation in healthcare associated pneumonia from electronic medical records data. BMC Infect Dis. 2015;15:197. doi: 10.1186/s12879-015-0933-9.
    1. Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, Corcia-Palomo Y, Fernandez-Delgado E, Herrera-Melero I, Ortiz-Leyba C, Marquez-Vacaro JA. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40:32–40. doi: 10.1007/s00134-013-3077-7.
    1. Dark P, Blackwood B, Gates S, McAuley D, Perkins GD, McMullan R, Wilson C, Graham D, Timms K, Warhurst G. Accuracy of LightCycler((R)) SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review and meta-analysis. Intensive Care Med. 2014;41:21–33. doi: 10.1007/s00134-014-3553-8.
    1. Chang SS, Hsieh WH, Liu TS, Lee SH, Wang CH, Chou HC, Yeo YH, Tseng CP, Lee CC. Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis—a systemic review and meta-analysis. PLoS ONE. 2013;8:e62323. doi: 10.1371/journal.pone.0062323.
    1. Avolio M, Diamante P, Modolo ML, De Rosa R, Stano P, Camporese A. Direct molecular detection of pathogens in blood as specific rule-in diagnostic biomarker in patients with presumed sepsis: our experience on a heterogeneous cohort of patients with signs of infective systemic inflammatory response syndrome. Shock. 2014;42:86–92. doi: 10.1097/SHK.0000000000000191.
    1. Ratzinger F, Tsirkinidou I, Haslacher H, Perkmann T, Schmetterer KG, Mitteregger D, Makristathis A, Burgmann H. Evaluation of the Septifast MGrade test on standard care wards-a cohort study. PLoS ONE. 2016;11:e0151108. doi: 10.1371/journal.pone.0151108.
    1. Cambau E, Bauer M. Multi-pathogen real-time PCR system adds benefit for my patients: yes. Intensive Care Med. 2015;41:528–530. doi: 10.1007/s00134-014-3639-3.
    1. Cambau E, Durand-Zaleski I, Bretagne S, Brun-Buisson C, Cordonnier C, Duval X, Herwegh S, Pottecher J, Courcol R, Bastuji-Garin S, The Evamica study team (2013) Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label cluster-randomised interventional crossover trial. ESCMID, Berlin, number 0673/3398
    1. Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, Moreillon P, de Jesus AM, Thilen U, Lekakis J, Lengyel M, Muller L, Naber CK, Nihoyannopoulos P, Moritz A, Zamorano JL. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009;30:2369–2413. doi: 10.1093/eurheartj/ehp285.
    1. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, Augustovski F, Briggs AH, Mauskopf J, Loder E, Force CT. Consolidated health economic evaluation reporting standards (CHEERS) statement. Value Health. 2013;16:e1–e5. doi: 10.1016/j.jval.2013.02.010.
    1. O’Brien BJ, Briggs AH. Analysis of uncertainty in health care cost-effectiveness studies: an introduction to statistical issues and methods. Stat Methods Med Res. 2002;11:455–468. doi: 10.1191/0962280202sm304ra.
    1. Briggs AH, O’Brien BJ. The death of cost-minimization analysis? Health Econ. 2001;10:179–184. doi: 10.1002/hec.584.
    1. Briggs AH, Mooney CZ, Wonderling DE. Constructing confidence intervals for cost-effectiveness ratios: an evaluation of parametric and non-parametric techniques using Monte Carlo simulation. Stat Med. 1999;18:3245–3262. doi: 10.1002/(SICI)1097-0258(19991215)18:23<3245::AID-SIM314>;2-2.
    1. Black WC. The CE plane: a graphic representation of cost-effectiveness. Med Decis Making. 1990;10:212–214. doi: 10.1177/0272989X9001000308.
    1. Campbell MK, Piaggio G, Elbourne DR, Altman DG, Group C Consort 2010 statement: extension to cluster randomised trials. BMJ. 2012;345:e5661. doi: 10.1136/bmj.e5661.
    1. Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, Gyssens IC, Kern WV, Klyasova G, Marchetti O, Engelhard D, Akova M (2013) European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 98:1826–1835
    1. Peters RP, van Agtmael MA, Danner SA, Savelkoul PH, Vandenbroucke-Grauls CM. New developments in the diagnosis of bloodstream infections. Lancet Infect Dis. 2004;4:751–760. doi: 10.1016/S1473-3099(04)01205-8.
    1. Varani S, Stanzani M, Paolucci M, Melchionda F, Castellani G, Nardi L, Landini M, Baccarani M, Pession A, Sambri V. Diagnosis of bloodstream infections in immunocompromised patients by real-time PCR. J Infect. 2009;58:346–351. doi: 10.1016/j.jinf.2009.03.001.
    1. Bloos F, Sachse S, Kortgen A, Pletz MW, Lehmann M, Straube E, Riedemann NC, Reinhart K, Bauer M. Evaluation of a polymerase chain reaction assay for pathogen detection in septic patients under routine condition: an observational study. PLoS ONE. 2013;7:e46003. doi: 10.1371/journal.pone.0046003.
    1. Potgieter M, Bester J, Kell DB, Pretorius E. The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev. 2015;39:567–591. doi: 10.1093/femsre/fuv013.
    1. Hall KK, Lyman JA. Updated review of blood culture contamination. Clin Microbiol Rev. 2006;19:788–802. doi: 10.1128/CMR.00062-05.
    1. SepNet Critical Care Trials G Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study. Intensive Care Med. 2016;42:1980–1989. doi: 10.1007/s00134-016-4504-3.
    1. Bassetti M, De Waele JJ, Eggimann P, Garnacho-Montero J, Kahlmeter G, Menichetti F, Nicolau DP, Paiva JA, Tumbarello M, Welte T, Wilcox M, Zahar JR, Poulakou G. Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Intensive Care Med. 2015;41:776–795. doi: 10.1007/s00134-015-3719-z.
    1. Alvarez J, Mar J, Varela-Ledo E, Garea M, Matinez-Lamas L, Rodriguez J, Regueiro B. Cost analysis of real-time polymerase chain reaction microbiological diagnosis in patients with septic shock. Anaesth Intensive Care. 2012;40:958–963.
    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The third international consensus definitions for sepsis and septic shock (sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287.
    1. Menezes LC, Rocchetti TT, Bauab Kde C, Cappellano P, Quiles MG, Carlesse F, de Oliveira JS, Pignatari AC. Diagnosis by real-time polymerase chain reaction of pathogens and antimicrobial resistance genes in bone marrow transplant patients with bloodstream infections. BMC Infect Dis. 2013;13:166. doi: 10.1186/1471-2334-13-166.
    1. Stevenson M, Pandor A, Martyn-St James M, Rafia R, Uttley L, Stevens J, Sanderson J, Wong R, Perkins GD, McMullan R, Dark P. Sepsis: the LightCycler SeptiFast Test MGRADE(R), SepsiTest and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi: a systematic review and economic evaluation. Health Technol Assess. 2016;20:1–246.
    1. Banerjee R, Teng CB, Cunningham SA, Ihde SM, Steckelberg JM, Moriarty JP, Shah ND, Mandrekar JN, Patel R. Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing. Clin Infect Dis. 2015;61:1071–1080. doi: 10.1093/cid/civ447.

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