Antifongique empirique et évolution chez les patients de réanimation.
Mots-clés :
antifongique; thérapie empirique; candidémie; septicémie nosocomiale; survieRésumé
Introduction: Le traitement de la candidose invasive (CI) demeure un défi en réanimation. L’administration tardive des antifongiques étant un facteur indépendant de mortalité. La prescription irraisonnable de ces agents est une source d’émergence de souches résistantes. Objectif: évaluer l’effet d’un traitement antifongique empirique (TAFE) sur la survie à J 28 et sur la survenue de candidémie chez les patients septiques sans infection candidosique prouvée.
Méthodes: étude de cohorte monocentrique, rétrospective sur 8 ans, comparant deux bras de patients septiques non neutropéniques sans infection fongique prouvée selon l'administration ou non d'un TAFE. Les 2 critères de jugement sont la mortalité à 28 jours et l'apparition de la candidémie. L'analyse a été ajustée sur le score APACHE II, le Candida score, la ventilation invasive et le cathétérisme central.
Résultats: 247 patients ont été inclus (groupe TAFE, n = 125 et groupe non TAFE, n = 122). Aucune amélioration de la survie à 28 jours n'a été trouvée. Ces résultats étaient concordants à l'analyse brute et après ajustement sur les facteurs mentionnés ci-dessus. Aucun effet préventif sur la survenue de candidémie. Un effet bénéfique du TAFE sur la survie a été observé chez des patients ayant un score APACHE II <16: OR= 0,68; IC 95% [0,53-0,87]; p=0,002.
Conclusions: aucun effet bénéfique d'un TAFE sur la survie à 28 jours ni sur la prévention de l'apparition d’une candidémie chez les patients septiques non neutropéniques de réanimation. Chez les patients ayant un score APACHE II < 16, il y avait un effet bénéfique sur la survie.
Téléchargements
Références
Bitar D, Lortholary O, Dromer F, Coignard B, Che D. Mycoses invasives en France métropolitaine, PMSI 2001-2010: incidence, létalité et tendances. Bull Epidemiol Hebd 2013;12-13:109-14.
Zilberberg MD, Shorr AF, Kollef MH. Secular trends in candidemia-related hospitalization in the United States, 2000-2005. Infect Control Hosp Epidemiol 2008;29:978-80.
Leroy O, Gangneux JP, Montravers P, Mira JP, Gouin F, Sollet JP, et al. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006). Crit Care Med 2009;37:1612-8.
Montagna MT, Caggiano G ,Lovero G, De Giglio O, Coretti C, Cuna T, et al. Epidemiology of invasive fungal infections in the intensive care unit: results of a multicenter Italian survey (AURORA Project). Infection 2013;41:645-53.
Bassetti M, Merelli M, Righi E, Diaz-Martin A, Rosello EM, Luzzati R, et al. Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J Clin Microbiol 2013;12:4167-72.
Lortholary O, Renaudat C, Sitbon K, Madec Y, Denoeud-Ndam L, Wolff M, et al. Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002-2010). Intensive Care Med 2014;40:1303-12.
Bassetti M, Righi E, Ansaldi F, Merelli M, Trucchi C, De Pascale G et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med 2014;40:839-45.
Cuenca-Estrella M, Verweij PE, Arendrup MC, Arikan-Akdagli S, Bille J, Donnelly JP, et al. ESCMID* guidelines for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Microbiol Infect 2012;7:9-18.
Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012;18:19-37.
León C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F, et al. A bedside scoring system ("Candida score") for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 2006;34:730-7.
Leroy G, Lambiotte F, Thévenin D, Lemaire C, Parmentier E, Devos P. Evaluation of ‘'Candida score'' in critically ill patients, a prospective, multicenter, observational, cohort study. Ann Intensive Care 2011;1:50.
Eggimann P, Ostrosky-Zeichner L. Early antifungal intervention strategies in ICU patients. Curr Opin Crit Care 2010;16:465-9.
Eggimann P, Bille J, Marchetti O. Diagnosis of invasive candidiasis in the ICU. Ann Intensive Care 2011;1:37.
Zilberberg MD, Kollef MH, Arnold H, et al. Inappropriate empiric antifungal therapy for candidemia in the ICU and hospital resource utilization: a retrospective cohort study. BMC Infect Dis 2010;10:150.
Grim SA, Berger K, Teng C, et al. Timing of susceptibility-based antifungal drug administration in patients with Candida bloodstream infection: correlation with outcomes. J Antimicrob Chemother 2012; 3:707-14.
Kollef M, Micek S, Hampton N, Doherty JA, Kumar A. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 2012;12:1739-46.
Fekkar A, Dannaoui E, Meyer I, et al. Emergence of echinocandin-resistant Candida spp. In a hospital setting: a consequence of 10 years of increasing use of antifungal therapy. Eur J Clin Microbiol Dis 2014; 33:1489-96.
Azoulay E, Dupont H, Tabah A, Lortholary O, Stahl JP, Français A, et al. Systemic antifungal therapy in critically ill patients without invasive fungal infection. Crit Care Med 2012;40:813 22.
Schuster MG, Edwards JE Jr, Sobel JD, , Darouiche RO, Karchmer AW, Hadley Set al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med 2008;149:83-90.
Ostrosky-Zeichner L, Shoham S, Vazquez J, Reboli A, Betts R, Barron MA, et al. MSG-01: a randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. Clin Infect Dis 2014;58:1219-26.
Timsit JF, Azoulay E, Schwebel C, Charles PE, Cornet M, Souweine B, et al. Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis,Candida Colonization, and Multiple Organ Failure: The EMPIRICUS Randomized Clinical Trial. JAMA 2016;316:1555-64.
Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock 2012. Guidelines Committee including the Pediatric Subgroup. Crit Care Med 2013;41:583.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-29.
Garey KW, Rege M, Pai MP, Mingo DE. Suda KJ, Turpin RS, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 2006;43:25-31.
Leroy O, Bailly S, Gangneux JP, Mira JP, Devos P, Dupont H, et al. Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study. Ann. Intensive Care 2016; 6:2.
Timsit JF, Azoulay E, Cornet M, Gangneux JP, Jullien V, Vésin A et al. EMPIRICUS micafungin versus placebo during nosocomial sepsis in Candida multi-colonized ICU patients with multiple organ failures: study protocol for a randomized controlled trial. Trials 2013;21:399.
Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis 2005;41:1232-39.
DiNubile MJ, Lupinacci RJ, Strohmaier KM, Sable CA, Kartsonis NA. Invasive candidiasis treated in the intensive care unit: observations from a randomized clinical trial. J Crit Care 2000; 22:237-44.
Playford EG, Eggimann P, Calandra T. Antifungals in the ICU. Curr Opin Infect Dis 2008;21:610-9.
Senn L, Eggimann P, Ksontini R, et al. Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients. Intensive Care Med 2009;35:903-8.
Knitsch W, Vincent JL, Utzolino S, François B, Dinya T, Dimopoulos G, et al. A randomized, placebo-controlled trial of pre-emptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections. Clin Infect Dis 2015;61:1671-8.
Eggimann P, Calandra T, Fluckiger U, Bille J, Garbino J, Glauser MP, et al. Invasive candidiasis: comparison of management choices by infectious disease and critical care specialists. Intensive Care Med 2005;31:1514-21.
Bassetti M, Trecarichi EM, Righi E, Sanguinetti M, Bisio F, Posteraro B, et al. Incidence, risk factors, and predictors of outcome of candidemia. Diagn Microbiol Infect Dis 2007;3:325-31.
Bailly S, Bouadhma L, Azoulay E, Orgeas MG, Adrie C, Souweine B, et al. Failure of Empirical Systemic Antifungal Therapy in Mechanically Ventilated Critically Ill Patients. Am J Respir Crit Care Med 2015;191:1139-46.
Cortegiani A, Russotto V, Maggiore A, Attanasio M, Naro AR, Raineri SM, et al. Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database of Systematic Reviews 2016; DOI: 10.1002/14651858.CD004920.
