Skip to main content
Top
Published in: Annals of Intensive Care 1/2018

Open Access 01-12-2018 | Research

De-escalation of antifungal treatment in critically ill patients with suspected invasive Candida infection: incidence, associated factors, and safety

Authors: Karim Jaffal, Julien Poissy, Anahita Rouze, Sébastien Preau, Boualem Sendid, Marjorie Cornu, Saad Nseir

Published in: Annals of Intensive Care | Issue 1/2018

Login to get access

Abstract

Background

Antifungal treatment is common in critically ill patients, but only a small proportion of patients receiving antifungals have a proven fungal infection. However, antifungal treatment has side effects such as toxicity, emergence of resistance, and high cost. Moreover, empirical antifungal treatment is still a matter for debate in these patients. Our study aimed to determine the incidence, associated factors, and safety of de-escalation of antifungals in critically ill patients.

Methods

This retrospective study was conducted in a 30-bed mixed ICU, from January 2012 through January 2013. Patients hospitalized for > 5 days and treated with antifungals for first suspected or proven invasive Candida infection were included. Exclusion criteria were prophylactic antifungals, suspected invasive aspergillosis, and neutropenia. De-escalation was defined as switch from initial systemic antifungals (except fluconazole) to triazoles, or stopping initial drugs within the 5 days following their initiation.

Results

One hundred and ninety patients were included. Antifungal treatment was empirical, preemptive, and targeted in 55, 27, and 24% of study patients, respectively. Caspofungin (53%), fluconazole (43%), voriconazole (4%), and liposomal amphotericin B (0.5%) were the more frequently used antifungals. De-escalation was performed in 38 (20%) patients. Invasive mechanical ventilation was independently associated with lower rates of de-escalation (OR 0.25 [95% CI 0.08–0.85], p = 0.013). Total duration of antifungal treatment was significantly shorter in patients with de-escalation, compared with those with no de-escalation (med [IQR] 6 (5, 18) vs. 13 days (7, 25), p = 0.023). No significant difference was found in duration of mechanical ventilation (22 [5–31] vs. 20 days [10–35], p = 0.43), length of ICU stay (25 [14–40) vs. 25 days [11–40], p = 0.99), ICU mortality (45 vs. 59%, p = 0.13), or 1-year mortality (55 vs. 64%, p = 0.33) between patients with de-escalation and those with no de-escalation, respectively.

Conclusions

De-escalation was performed in 20% of patients receiving systemic antifungals for suspected or proven invasive Candida infection. Mechanical ventilation was independently associated with lower rates of de-escalation. De-escalation of antifungal treatment seems to be safe in critically ill patients.
Literature
1.
go back to reference León C, Ostrosky-Zeichner L, Schuster M. What’s new in the clinical and diagnostic management of invasive candidiasis in critically ill patients. Intensive Care Med. 2014;40:808–19.CrossRefPubMed León C, Ostrosky-Zeichner L, Schuster M. What’s new in the clinical and diagnostic management of invasive candidiasis in critically ill patients. Intensive Care Med. 2014;40:808–19.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
3.
go back to reference Leroy O, Bailly S, Gangneux J-P, Mira J-P, 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.CrossRefPubMedPubMedCentral Leroy O, Bailly S, Gangneux J-P, Mira J-P, 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.CrossRefPubMedPubMedCentral
4.
go back to reference Vincent J-L, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.CrossRefPubMed Vincent J-L, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–9.CrossRefPubMed
5.
go back to reference Kett DH, Azoulay E, Echeverria PM, Vincent J-L. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med. 2011;39:665–70.CrossRefPubMed Kett DH, Azoulay E, Echeverria PM, Vincent J-L. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med. 2011;39:665–70.CrossRefPubMed
6.
go back to reference Bassetti M, Righi E, Ansaldi F, Merelli M, Trucchi C, Cecilia T, et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med. 2014;40:839–45.CrossRefPubMed Bassetti M, Righi E, Ansaldi F, Merelli M, Trucchi C, Cecilia T, et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med. 2014;40:839–45.CrossRefPubMed
7.
go back to reference Ostrosky-Zeichner L, Kullberg BJ, Bow EJ, Hadley S, León C, Nucci M, et al. Early treatment of candidemia in adults: a review. Med Mycol. 2011;49:113–20.CrossRefPubMed Ostrosky-Zeichner L, Kullberg BJ, Bow EJ, Hadley S, León C, Nucci M, et al. Early treatment of candidemia in adults: a review. Med Mycol. 2011;49:113–20.CrossRefPubMed
8.
9.
go back to reference León C, Álvarez-Lerma F, Ruiz-Santana S, León MÁ, Nolla J, Jordá R, et al. Fungal colonization and/or infection in non-neutropenic critically ill patients: results of the EPCAN observational study. Eur J Clin Microbiol Infect Dis. 2009;28:233–42.CrossRefPubMed León C, Álvarez-Lerma F, Ruiz-Santana S, León MÁ, Nolla J, Jordá R, et al. Fungal colonization and/or infection in non-neutropenic critically ill patients: results of the EPCAN observational study. Eur J Clin Microbiol Infect Dis. 2009;28:233–42.CrossRefPubMed
10.
go back to reference Arvanitis M, Anagnostou T, Fuchs BB, Caliendo AM, Mylonakis E. Molecular and nonmolecular diagnostic methods for invasive fungal infections. Clin Microbiol Rev. 2014;27:490–526.CrossRefPubMedPubMedCentral Arvanitis M, Anagnostou T, Fuchs BB, Caliendo AM, Mylonakis E. Molecular and nonmolecular diagnostic methods for invasive fungal infections. Clin Microbiol Rev. 2014;27:490–526.CrossRefPubMedPubMedCentral
11.
go back to reference Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284–92.CrossRefPubMed Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284–92.CrossRefPubMed
12.
go back to reference 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;54:1739–46.CrossRefPubMed 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;54:1739–46.CrossRefPubMed
13.
go back to reference Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;62:e1–50.CrossRefPubMed Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;62:e1–50.CrossRefPubMed
14.
go back to reference Azoulay E, Dupont H, Tabah A, Lortholary O, Stahl J-P, Francais A, et al. Systemic antifungal therapy in critically ill patients without invasive fungal infection. Crit Care Med. 2012;40:813–22.CrossRefPubMed Azoulay E, Dupont H, Tabah A, Lortholary O, Stahl J-P, Francais A, et al. Systemic antifungal therapy in critically ill patients without invasive fungal infection. Crit Care Med. 2012;40:813–22.CrossRefPubMed
15.
go back to reference Arendrup MC, Dzajic E, Jensen RH, Johansen HK, Kjaeldgaard P, Knudsen JD, et al. Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme. Clin Microbiol Infect. 2013;19:E343–53.CrossRefPubMed Arendrup MC, Dzajic E, Jensen RH, Johansen HK, Kjaeldgaard P, Knudsen JD, et al. Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme. Clin Microbiol Infect. 2013;19:E343–53.CrossRefPubMed
16.
go back to reference Ostrosky-Zeichner L. Candida glabrata and FKS mutations: witnessing the emergence of the true multidrug-resistant Candida. Clin Infect Dis. 2013;56:1733–4.CrossRefPubMed Ostrosky-Zeichner L. Candida glabrata and FKS mutations: witnessing the emergence of the true multidrug-resistant Candida. Clin Infect Dis. 2013;56:1733–4.CrossRefPubMed
17.
go back to reference Lortholary O, Desnos-Ollivier M, Sitbon K, Fontanet A, Bretagne S, Dromer F, et al. Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients. Antimicrob Agents Chemother. 2011;55:532–8.CrossRefPubMed Lortholary O, Desnos-Ollivier M, Sitbon K, Fontanet A, Bretagne S, Dromer F, et al. Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients. Antimicrob Agents Chemother. 2011;55:532–8.CrossRefPubMed
18.
go back to reference Dannaoui E, Desnos-Ollivier M, Garcia-Hermoso D, Grenouillet F, Cassaing S, Baixench M-T, et al. Candida spp. with acquired echinocandin resistance, France, 2004–2010. Emerg Infect Dis. 2012;18:86–90.CrossRefPubMedPubMedCentral Dannaoui E, Desnos-Ollivier M, Garcia-Hermoso D, Grenouillet F, Cassaing S, Baixench M-T, et al. Candida spp. with acquired echinocandin resistance, France, 2004–2010. Emerg Infect Dis. 2012;18:86–90.CrossRefPubMedPubMedCentral
20.
go back to reference Valerio M, Rodriguez-Gonzalez CG, Munoz P, Caliz B, Sanjurjo M, Bouza E, et al. Evaluation of antifungal use in a tertiary care institution: antifungal stewardship urgently needed. J Antimicrob Chemother. 2014;69:1993–9.CrossRefPubMed Valerio M, Rodriguez-Gonzalez CG, Munoz P, Caliz B, Sanjurjo M, Bouza E, et al. Evaluation of antifungal use in a tertiary care institution: antifungal stewardship urgently needed. J Antimicrob Chemother. 2014;69:1993–9.CrossRefPubMed
21.
go back to reference Playford EG, Webster AC, Sorrell TC, Craig JC. Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials. J Antimicrob Chemother. 2006;57:628–38.CrossRefPubMed Playford EG, Webster AC, Sorrell TC, Craig JC. Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials. J Antimicrob Chemother. 2006;57:628–38.CrossRefPubMed
22.
go back to reference Schuster MG, Edwards JE, Sobel JD, Darouiche RO, Karchmer AW, Hadley S, et al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med. 2008;149:83–90.CrossRefPubMed Schuster MG, Edwards JE, Sobel JD, Darouiche RO, Karchmer AW, Hadley S, et al. Empirical fluconazole versus placebo for intensive care unit patients: a randomized trial. Ann Intern Med. 2008;149:83–90.CrossRefPubMed
23.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
24.
go back to reference Takesue Y, Ueda T, Mikamo H, Oda S, Takakura S, Kitagawa Y, et al. Management bundles for candidaemia: the impact of compliance on clinical outcomes. J Antimicrob Chemother [Internet]. 2015;70:587–93.CrossRefPubMed Takesue Y, Ueda T, Mikamo H, Oda S, Takakura S, Kitagawa Y, et al. Management bundles for candidaemia: the impact of compliance on clinical outcomes. J Antimicrob Chemother [Internet]. 2015;70:587–93.CrossRefPubMed
25.
go back to reference Vazquez J, Reboli AC, Pappas PG, Patterson TF, Reinhardt J, Chin-Hong P, et al. Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial. BMC Infect Dis. 2014;14:97.CrossRefPubMedPubMedCentral Vazquez J, Reboli AC, Pappas PG, Patterson TF, Reinhardt J, Chin-Hong P, et al. Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial. BMC Infect Dis. 2014;14:97.CrossRefPubMedPubMedCentral
26.
27.
go back to reference De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21. https://doi.org/10.1086/588660.CrossRefPubMedPubMedCentral De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21. https://​doi.​org/​10.​1086/​588660.CrossRefPubMedPubMedCentral
28.
go back to reference Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the infectious diseases society of America. Clin Infect Dis. 2009;48:503–35.CrossRefPubMed Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the infectious diseases society of America. Clin Infect Dis. 2009;48:503–35.CrossRefPubMed
29.
go back to reference Zein M, Parmentier-Decrucq E, Kalaoun A, Bouton O, Wallyn F, Baranzelli A, et al. Factors predicting prolonged empirical antifungal treatment in critically ill patients. Ann Clin Microbiol Antimicrob. 2014;13:11.CrossRefPubMedPubMedCentral Zein M, Parmentier-Decrucq E, Kalaoun A, Bouton O, Wallyn F, Baranzelli A, et al. Factors predicting prolonged empirical antifungal treatment in critically ill patients. Ann Clin Microbiol Antimicrob. 2014;13:11.CrossRefPubMedPubMedCentral
32.
go back to reference López-Cortés LE, Almirante B, Cuenca-Estrella M, Garnacho-Montero J, Padilla B, Puig-Asensio M, et al. Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort. Clin Microbiol Infect. 2016;22(733):e1–8. López-Cortés LE, Almirante B, Cuenca-Estrella M, Garnacho-Montero J, Padilla B, Puig-Asensio M, et al. Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort. Clin Microbiol Infect. 2016;22(733):e1–8.
34.
go back to reference Timsit J-F, 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. JAMA. 2016;316:1555.CrossRefPubMed Timsit J-F, 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. JAMA. 2016;316:1555.CrossRefPubMed
35.
go back to reference Bal AM, Shankland GS, Scott G, Imtiaz T, Macaulay R, McGill M. Antifungal step-down therapy based on hospital intravenous to oral switch policy and susceptibility testing in adult patients with candidaemia: a single centre experience. Int J Clin Pract. 2014;68:20–7.CrossRefPubMed Bal AM, Shankland GS, Scott G, Imtiaz T, Macaulay R, McGill M. Antifungal step-down therapy based on hospital intravenous to oral switch policy and susceptibility testing in adult patients with candidaemia: a single centre experience. Int J Clin Pract. 2014;68:20–7.CrossRefPubMed
36.
go back to reference Rouzé A, Jaffal K, Nseir S. How could we reduce antifungal treatment in the intensive care unit. World J Clin Infect Dis. 2015;5:55–8.CrossRef Rouzé A, Jaffal K, Nseir S. How could we reduce antifungal treatment in the intensive care unit. World J Clin Infect Dis. 2015;5:55–8.CrossRef
37.
go back to reference Rouzé A, Loridant S, Poissy J, Dervaux B, Sendid B, Cornu M, et al. Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial. Intensive Care Med. 2017;43(11):1668–77.CrossRefPubMed Rouzé A, Loridant S, Poissy J, Dervaux B, Sendid B, Cornu M, et al. Biomarker-based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomized controlled trial. Intensive Care Med. 2017;43(11):1668–77.CrossRefPubMed
Metadata
Title
De-escalation of antifungal treatment in critically ill patients with suspected invasive Candida infection: incidence, associated factors, and safety
Authors
Karim Jaffal
Julien Poissy
Anahita Rouze
Sébastien Preau
Boualem Sendid
Marjorie Cornu
Saad Nseir
Publication date
01-12-2018
Publisher
Springer International Publishing
Published in
Annals of Intensive Care / Issue 1/2018
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-018-0392-8

Other articles of this Issue 1/2018

Annals of Intensive Care 1/2018 Go to the issue