De-escalation - Antifungal Treatment Immunocompromised Patients

Study Overview
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Brief Summary
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A small proportion of intensive care unit patients receiving antifungals have a proven invasive 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 immunocompromised critically ill patients. This prospective observational study is conducted in 14 ICU, during a 6 months period. All immunocompromised patients hospitalized for >5d and treated with antifungals for suspected or proven invasive candida infection will be included De-escalation is defined as a reduction in antifungal spectrum or stopping initial drugs within the 5 days following their initiation. The three antifungals considered in this study are from the narrowest to the widest spectrum: fluconazole, caspofungin and liposomal amphotericin B.

Detailed Description
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This is a retrospective and prospective observational multicenter study, aiming to determine the incidence, and safety of antifungal de-escalation in immunocompromised patients, and also factors associated with de-escalation.

Official Title
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De-escalation of Antifungal Treatment in Immunocompromised Critically Ill Patients With Suspected Invasive Candida Infection: Incidence, Associated Factors, and Safety

Conditions
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Invasive Fungal Disease, Critical Illness

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults immunocompromised patients hospitalized in intensive care units Predictable invasive mechanical ventilation duration > 96h Signed consent (by patient or its representative) First antifungal treatment initiation in ICU for proven or suspected candida infection Exclusion Criteria: Pregnant or breast-feeding women. Fungal infection other than invasive candida Prophylactic antifungal treatment. Lack of informed consent Predictable mechanical ventilation duration less than 48 hours Patients discharged from ICU before the 5th day after initiation of TAF

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with de-escalation of antifungal treatment | De-escalation is defined as a reduction in antifungal treatment spectrum (switch from echinocandines or Amphotericin B to Azoles) or stopping all antifungals within the 5 days following their initiation | 5 days following start of antifungal treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk factors for de-escalation of antifungal therapy | Clinical characteristics and conditions significantly associated with de-escalation by univariate analysis will be entered in a multiple regression model to determine those independently associated with de-escalation | during the 5 days following start of antifungal | 
| Number of days free of mechanical ventilation | days with no mechanical ventilation | until day 28 after start of antifungal treatment | 
| Number of days free of antifungal treatment | days with no antifungal treatment | until day 28 after start of antifungal treatment | 
| Length of ICU stay | days in the ICU | until day 28 after start of antifungal treatment | 
| All-cause mortality | mortality related to any cause | until day 28 after start of antifungal treatment | 
| Percentage of patients with reoccurrence of candidiasis | reccurrence of candidiasis is defined as a new episode after the end of antifungal treatment | until day 7 after stop of antifungal treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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De-escalation, Antifungal treatment, Mortality, Immunocompromised, Intensive care