Empiric antifungal and outcome in ICU patients.

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Published Oct 7, 2019
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Vol. 97 No. 4 (2019): Issue Apr 2019

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Ahlem Trifi
Sami Abdellatif
Foued Daly
Rochdi Nasri
Yosr Touil
Salah Ben Lakhal

Abstract

Background: The management of invasive candidiasis (IC) remains a major challenge in intensive care units (ICU). On the one hand, it becomes admitted that delayed antifungal is an independent mortality factor. In the other hand, the unreasonable administration of antifungal agents is implicated in emergence of resistant Candida strains.
 Aim: to evaluate whether empirical antifungal therapy (EAFT) improves survival at day 28 and prevents a new episode of candidemia in septic patients without proven Candida infection.
Methods: a 8-years retrospective double cohort, monocentric study, comparing two arms of ICU non neutropenic septic patients without proven fungal infection according to administration or not of an EAFT. The primary outcome was the 28-day mortality and the second was the occurrence of candidemia. The analysis was adjusted on Acute Physiology And Chronic Health Evaluation II (APACHE II) score, Candida score, invasive ventilation and central catheterisation.
Results:  247 patients were included (EAFT group, n=125 and non EAFT group, n=122). No improvement of 28-day survival was found. These results were in accordance both in crude analysis and after adjusting on factors mentioned above. No preventing effect on a new episode of candidemia. Nevertheless, a beneficial effect of EAFT on survival was found in patients with an APACHE II score<16: OR=0.68; CI 95% [0.53-0.87]; p=0.002.
Conclusions: no beneficial impact of an EAFT on 28- day survival neither in preventing the occurrence of candidemia in non neutropenic septic critically patients. In patients with APACHE II score less than 16, there was a beneficial effect on survival.

Keywords:

antifungal; empiric Therapy; candidemia; nosocomial sepsis; survival

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References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. Eggimann P, Ostrosky-Zeichner L. Early antifungal intervention strategies in ICU patients. Curr Opin Crit Care 2010;16:465-9.
  13. Eggimann P, Bille J, Marchetti O. Diagnosis of invasive candidiasis in the ICU. Ann Intensive Care 2011;1:37.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-29.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. Playford EG, Eggimann P, Calandra T. Antifungals in the ICU. Curr Opin Infect Dis 2008;21:610-9.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. 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.
  35. 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.