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Published in: Intensive Care Medicine 11/2020

01-11-2020 | Candidiasis | Narrative Review

Invasive candidiasis in critical care: challenges and future directions

Authors: C. Logan, I. Martin-Loeches, T. Bicanic

Published in: Intensive Care Medicine | Issue 11/2020

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Abstract

Invasive candidiasis is the most common critical care-associated fungal infection with a crude mortality of ~ 40–55%. Important factors contributing to risk of invasive candidiasis in ICU include use of broad-spectrum antimicrobials, immunosuppressive drugs, and total parenteral nutrition alongside iatrogenic interventions which breach natural barriers to infection [vascular catheters, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), surgery]. This review discusses three key challenges in this field. The first is the shift in Candida epidemiology across the globe to more resistant non-albicans species, in particular, the emergence of multi-resistant Candida glabrata and Candida auris, which pose significant treatment and infection control challenges in critical care. The second challenge lies in the timely and appropriate initiation and discontinuation of antifungal therapy. Early antifungal strategies (prophylaxis, empirical and pre-emptive) using tools such as the Candida colonisation index, clinical prediction rules and fungal non-culture-based tests have been developed: we review the evidence on implementation of these tools in critical care to aid clinical decision-making around the prescribing and cessation of antifungal therapy. The third challenge is selection of the most appropriate antifungal to use in critical care patients. While guidelines exist to aid choice, this heterogenous and complex patient group require a more tailored approach, particularly in cases of acute kidney injury, liver impairment and for patients supported by extracorporeal membrane oxygenation. We highlight key research priorities to overcome these challenges in the future.
Literature
9.
go back to reference Kullberg BJ, Arendrup MC (2015) Invasive candidiasis. N Engl J Med 373:1445–1456CrossRef Kullberg BJ, Arendrup MC (2015) Invasive candidiasis. N Engl J Med 373:1445–1456CrossRef
14.
go back to reference Bell T, O’Grady NP (2017) Prevention of central line-associated bloodstream infections. Infect Dis Clin N Am 31:551–559CrossRef Bell T, O’Grady NP (2017) Prevention of central line-associated bloodstream infections. Infect Dis Clin N Am 31:551–559CrossRef
17.
go back to reference Montagna MT, Caggiano G, Lovero G et al (2013) Epidemiology of invasive fungal infections in the intensive care unit: results of a multicenter Italian survey (AURORA project). Infection 41:645–653CrossRef Montagna MT, Caggiano G, Lovero G et al (2013) Epidemiology of invasive fungal infections in the intensive care unit: results of a multicenter Italian survey (AURORA project). Infection 41:645–653CrossRef
22.
24.
26.
go back to reference Vallabhaneni S, Cleveland AA, Farley MM et al (2015) Epidemiology and risk factors for echinocandin nonsusceptible Candida glabrata bloodstream infections: data from a large multisite population-based candidemia surveillance program, 2008–2014. Open Forum Infect Dis. https://doi.org/10.1093/ofid/ofv163CrossRef Vallabhaneni S, Cleveland AA, Farley MM et al (2015) Epidemiology and risk factors for echinocandin nonsusceptible Candida glabrata bloodstream infections: data from a large multisite population-based candidemia surveillance program, 2008–2014. Open Forum Infect Dis. https://​doi.​org/​10.​1093/​ofid/​ofv163CrossRef
28.
go back to reference Cortegiani A, Misseri G, Chowdhary A (2019) What’s new on emerging resistant Candida species. Intensive Care Med 45:512–515CrossRef Cortegiani A, Misseri G, Chowdhary A (2019) What’s new on emerging resistant Candida species. Intensive Care Med 45:512–515CrossRef
32.
38.
go back to reference Ku TSN, Walraven CJ, Lee SA (2018) Candida auris: disinfectants and implications for infection control. Front Microbiol 9:726CrossRef Ku TSN, Walraven CJ, Lee SA (2018) Candida auris: disinfectants and implications for infection control. Front Microbiol 9:726CrossRef
48.
go back to reference Haydour Q, Hage CA, Carmona EM et al (2019) Diagnosis of fungal infections a systematic review and meta-analysis supporting American thoracic society practice guideline. Ann Am Thorac Soc 16:1179–1188CrossRef Haydour Q, Hage CA, Carmona EM et al (2019) Diagnosis of fungal infections a systematic review and meta-analysis supporting American thoracic society practice guideline. Ann Am Thorac Soc 16:1179–1188CrossRef
50.
go back to reference He S, Hang JP, Zhang L et al (2015) A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-β-d-glucan for invasive fungal infection: focus on cutoff levels. J Microbiol Immunol Infect 48:351–361CrossRef He S, Hang JP, Zhang L et al (2015) A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-β-d-glucan for invasive fungal infection: focus on cutoff levels. J Microbiol Immunol Infect 48:351–361CrossRef
51.
go back to reference Mikulska M, Calandra T, Sanguinetti M et al (2010) The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European conference on Infections in Leukemia. Crit Care. https://doi.org/10.1186/cc9365CrossRef Mikulska M, Calandra T, Sanguinetti M et al (2010) The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European conference on Infections in Leukemia. Crit Care. https://​doi.​org/​10.​1186/​cc9365CrossRef
57.
go back to reference Ostrosky-Zeichner L, Shoham S, Vazquez J et al (2014) 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 58:1219–1226. https://doi.org/10.1093/cid/ciu074CrossRef Ostrosky-Zeichner L, Shoham S, Vazquez J et al (2014) 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 58:1219–1226. https://​doi.​org/​10.​1093/​cid/​ciu074CrossRef
58.
go back to reference Knitsch W, Vincent J-L, Utzolino S et al (2015) A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections. Clin Infect Dis 61:1671–1678. https://doi.org/10.1093/cid/civ707CrossRef Knitsch W, Vincent J-L, Utzolino S et al (2015) A randomized, placebo-controlled trial of preemptive antifungal therapy for the prevention of invasive candidiasis following gastrointestinal surgery for intra-abdominal infections. Clin Infect Dis 61:1671–1678. https://​doi.​org/​10.​1093/​cid/​civ707CrossRef
59.
go back to reference Timsit JF, Azoulay E, Schwebel C et al (2016) 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. J Am Med Assoc 316:1555–1564. https://doi.org/10.1001/jama.2016.14655CrossRef Timsit JF, Azoulay E, Schwebel C et al (2016) 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. J Am Med Assoc 316:1555–1564. https://​doi.​org/​10.​1001/​jama.​2016.​14655CrossRef
64.
go back to reference Garbino J, Lew DP, Romand JA et al (2002) Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Intensive Care Med 28:1708–1717. https://doi.org/10.1007/s00134-002-1540-yCrossRef Garbino J, Lew DP, Romand JA et al (2002) Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Intensive Care Med 28:1708–1717. https://​doi.​org/​10.​1007/​s00134-002-1540-yCrossRef
68.
go back to reference Harrison D, Muskett H, Harvey S et al (2013) Development and validation of a risk model for identification of non-neutropenic, critically-ill, adult patients at high risk of invasive Candida infection. Health Technol Assess (Rockv) 17:1–30. https://doi.org/10.3310/hta17030CrossRef Harrison D, Muskett H, Harvey S et al (2013) Development and validation of a risk model for identification of non-neutropenic, critically-ill, adult patients at high risk of invasive Candida infection. Health Technol Assess (Rockv) 17:1–30. https://​doi.​org/​10.​3310/​hta17030CrossRef
69.
go back to reference Clancy CJ, Nguyen MH (2018) Non-culture diagnostics for invasive candidiasis: promise and unintended consequences. J Fungi 4:27CrossRef Clancy CJ, Nguyen MH (2018) Non-culture diagnostics for invasive candidiasis: promise and unintended consequences. J Fungi 4:27CrossRef
70.
go back to reference Cortegiani A, Russotto V, Maggiore A et al (2016) Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database Syst Rev 1:CD004920 Cortegiani A, Russotto V, Maggiore A et al (2016) Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database Syst Rev 1:CD004920
75.
83.
go back to reference Hage CA, Carmona EM, Epelbaum O et al (2019) Microbiological laboratory testing in the diagnosis of fungal infections in pulmonary and critical care practice: an official American thoracic society clinical practice guideline. Am J Respir Crit Care Med 200:535–550CrossRef Hage CA, Carmona EM, Epelbaum O et al (2019) Microbiological laboratory testing in the diagnosis of fungal infections in pulmonary and critical care practice: an official American thoracic society clinical practice guideline. Am J Respir Crit Care Med 200:535–550CrossRef
84.
go back to reference Mylonakis E, Zacharioudakis IM, Clancy CJ et al (2018) Efficacy of T2 magnetic resonance assay in monitoring candidemia after initiation of antifungal therapy: the serial therapeutic and antifungal monitoring protocol (STAMP) trial. J Clin Microbiol 56:e01756–e1817. https://doi.org/10.1128/JCM.01756-17CrossRef Mylonakis E, Zacharioudakis IM, Clancy CJ et al (2018) Efficacy of T2 magnetic resonance assay in monitoring candidemia after initiation of antifungal therapy: the serial therapeutic and antifungal monitoring protocol (STAMP) trial. J Clin Microbiol 56:e01756–e1817. https://​doi.​org/​10.​1128/​JCM.​01756-17CrossRef
91.
93.
go back to reference Pappas PG, Kauffman CA, Andes DR et al (2015) Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis 62:e1–e50 Pappas PG, Kauffman CA, Andes DR et al (2015) Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis 62:e1–e50
96.
go back to reference Kett DH, Shorr AF, Reboli AC et al (2011) Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: support for the 2009 IDSA treatment guidelines for candidiasis. Crit Care 15:R253. https://doi.org/10.1186/cc10514CrossRef Kett DH, Shorr AF, Reboli AC et al (2011) Anidulafungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis: support for the 2009 IDSA treatment guidelines for candidiasis. Crit Care 15:R253. https://​doi.​org/​10.​1186/​cc10514CrossRef
97.
101.
go back to reference Colombo AL, Guimarães T, Sukienik T et al (2014) Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period. Intensive Care Med 40:1489–1498. https://doi.org/10.1007/s00134-014-3400-yCrossRef Colombo AL, Guimarães T, Sukienik T et al (2014) Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period. Intensive Care Med 40:1489–1498. https://​doi.​org/​10.​1007/​s00134-014-3400-yCrossRef
103.
go back to reference Keane S, Geoghegan P, Povoa P et al (2018) Systematic review on the first line treatment of amphotericin B in critically ill adults with candidemia or invasive candidiasis. Expert Rev Anti Infect Ther 16:839–847CrossRef Keane S, Geoghegan P, Povoa P et al (2018) Systematic review on the first line treatment of amphotericin B in critically ill adults with candidemia or invasive candidiasis. Expert Rev Anti Infect Ther 16:839–847CrossRef
104.
go back to reference Vazquez J, Reboli AC, Pappas PG et al (2014) 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. https://doi.org/10.1186/1471-2334-14-97CrossRef Vazquez J, Reboli AC, Pappas PG et al (2014) 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. https://​doi.​org/​10.​1186/​1471-2334-14-97CrossRef
105.
go back to reference Tabah A, Bassetti M, Kollef MH et al (2020) Antimicrobial de-escalation in critically ill patients: a position statement from a task force of the European Society of Intensive Care Medicine (ESICM) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Critically Ill Patients Study Group (ESGCIP). Intensive Care Med 46:245–265. https://doi.org/10.1007/s00134-019-05866-wCrossRef Tabah A, Bassetti M, Kollef MH et al (2020) Antimicrobial de-escalation in critically ill patients: a position statement from a task force of the European Society of Intensive Care Medicine (ESICM) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Critically Ill Patients Study Group (ESGCIP). Intensive Care Med 46:245–265. https://​doi.​org/​10.​1007/​s00134-019-05866-wCrossRef
106.
go back to reference Chatelon J, Cortegiani A, Hammad E et al (2019) Choosing the right antifungal agent in ICU patients. Adv Ther 36:3308–3320CrossRef Chatelon J, Cortegiani A, Hammad E et al (2019) Choosing the right antifungal agent in ICU patients. Adv Ther 36:3308–3320CrossRef
107.
go back to reference Bellmann R, Smuszkiewicz P (2017) Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients. Infection 45:737–779CrossRef Bellmann R, Smuszkiewicz P (2017) Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients. Infection 45:737–779CrossRef
108.
go back to reference González de Molina FJ, de Martínez-Alberici MLA, Ferrer R (2014) Treatment with echinocandins during continuous renal replacement therapy. Crit Care 18:218CrossRef González de Molina FJ, de Martínez-Alberici MLA, Ferrer R (2014) Treatment with echinocandins during continuous renal replacement therapy. Crit Care 18:218CrossRef
109.
go back to reference Tverdek FP, Kofteridis D, Kontoyiannis DP (2016) Antifungal agents and liver toxicity: a complex interaction. Expert Rev Anti Infect Ther 14:765–776CrossRef Tverdek FP, Kofteridis D, Kontoyiannis DP (2016) Antifungal agents and liver toxicity: a complex interaction. Expert Rev Anti Infect Ther 14:765–776CrossRef
111.
go back to reference Sherwin J, Heath T, Watt K (2016) Pharmacokinetics and dosing of anti-infective drugs in patients on extracorporeal membrane oxygenation: a review of the current literature. Clin Ther 38:1976–1994CrossRef Sherwin J, Heath T, Watt K (2016) Pharmacokinetics and dosing of anti-infective drugs in patients on extracorporeal membrane oxygenation: a review of the current literature. Clin Ther 38:1976–1994CrossRef
112.
go back to reference Watt KM, Cohen-Wolkowiez M, Williams DC et al (2017) Antifungal extraction by the extracorporeal membrane oxygenation circuit. J Extra Corpor Technol 49:150–159 Watt KM, Cohen-Wolkowiez M, Williams DC et al (2017) Antifungal extraction by the extracorporeal membrane oxygenation circuit. J Extra Corpor Technol 49:150–159
113.
go back to reference Ruiz S, Papy E, Da Silva D et al (2009) Potential voriconazole and caspofungin sequestration during extracorporeal membrane oxygenation. Intensive Care Med 35:183–184CrossRef Ruiz S, Papy E, Da Silva D et al (2009) Potential voriconazole and caspofungin sequestration during extracorporeal membrane oxygenation. Intensive Care Med 35:183–184CrossRef
117.
go back to reference Watt KM, Gonzalez D, Benjamin DK et al (2015) Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive candidiasis in children supported with extracorporeal membrane oxygenation. Antimicrob Agents Chemother 59:3935–3943. https://doi.org/10.1128/AAC.00102-15CrossRef Watt KM, Gonzalez D, Benjamin DK et al (2015) Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive candidiasis in children supported with extracorporeal membrane oxygenation. Antimicrob Agents Chemother 59:3935–3943. https://​doi.​org/​10.​1128/​AAC.​00102-15CrossRef
Metadata
Title
Invasive candidiasis in critical care: challenges and future directions
Authors
C. Logan
I. Martin-Loeches
T. Bicanic
Publication date
01-11-2020
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 11/2020
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-020-06240-x

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