Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for Screening Antifungal Exposure in Intensive Care Units—the SAFE-ICU study

Intensive Care Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Appropriate antifungal therapy is a major determinant of survival in critically ill patients with invasive fungal disease. We sought to describe whether contemporary dosing antifungals achieves therapeutic exposures patients. In prospective, open-label, multicenter pharmacokinetic study, intensive care unit (ICU) prescribed azoles, echinocandins, or polyene for treatment prophylaxis disease were enrolled. Blood samples collected on two occasions, three taken during single interval each occasion. Total concentrations centrally measured using validated chromatographic methods. Pharmacokinetic parameters estimated noncompartmental Antifungal adequacy was assessed predefined PK/PD targets. included 339 from 30 ICUs across 12 countries. Median age 62 (interquartile range [IQR], 51-70) years, median APACHE II score 22 (IQR, 17-28), and 61% males. primarily (80.8%). Fluconazole the most frequently (40.7%). The common indication intra-abdominal infection (30.7%). Fungi identified 45% patients, which only 26% had minimum inhibitory concentration available. Target attainment higher receiving (> 80% drugs). For treatment, low target noted voriconazole (57.1%), posaconazole (63.2%), micafungin (64.1%) amphotericin B (41.7%). This study highlights varying degrees agents While significant proportion achieved targets, wide variability subtherapeutic persist. ClinicalTrials.gov Identifier: NCT03136926, 2017-04-21.

Language: Английский

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Invasive Aspergillosis in the Intensive Care Unit

Journal of Fungi, Journal Year: 2025, Volume and Issue: 11(1), P. 70 - 70

Published: Jan. 17, 2025

Invasive aspergillosis (IA) is a fungal infection, which has traditionally been associated with neutropenia and immunosuppressive therapies. Our understanding of invasive evolving and, in the past few decades, IA among ICU patients recognized as common infection become more widely recognized. The diagnosis management particularly challenging, due to unstable clinical condition patients, lack diagnostic markers, increased risk further deterioration, multiple comorbidities, need for early assessment treatment. In this article, we will discuss challenges pitfalls an setting, along review current literature that pertinent specific population.

Language: Английский

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Current Antifungals and the Developing Pipeline

Infectious Disease Clinics of North America, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Invasive Aspergillosis in the Current Era

Infectious Disease Clinics of North America, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Pharmacokinetic novelties of isavuconazole. Use in special situations

Revista Iberoamericana de Micología, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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An Overview of Isavuconazole Clinical Use: A Multicentre Analysis of Indications, Exposure and Hepatic Safety

Clinical Drug Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Isavuconazole is a recent broad-spectrum triazole indicated for the treatment of invasive aspergillosis and mucormycosis when amphotericin B inappropriate. However, limited information exists on its clinical use. We set up retrospective multicentre study to describe practice isavuconazole including indications, exposure, hepatic safety. From January 2021 June 2023, all patients who received had at least one therapeutic drug monitoring (TDM) measurement, were included. To identify independent predictors trough concentrations (Cmin), linear regression analyses performed. Causal relationship between occurrence liver injury was also analysed. Most included (n = 102) admitted into haematology units (41.1% [n 42]) or intensive care (ICU) (30.4% 31]). Aspergillosis (47.0% 48]), (25.6% 26]), off-label empirical treatments (18.6% 19]), three most common indications. About half (46.1% 47]) an optimal while 42.2% 43) underexposed, 11.7% 12) overexposed. Albumin level day TDM significant factor associated with increase in Cmin (p 0.010). Among 11 test abnormalities, discontinued six 6) attributable two 2) patients. This analysis highlighted use as indication, well frequent underexposure isavuconazole. appeared be important driving especially ICU

Language: Английский

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Role of liposomal amphotericin B in intensive care unit: an expert opinion paper

Journal of Anesthesia Analgesia and Critical Care, Journal Year: 2025, Volume and Issue: 5(1)

Published: April 29, 2025

Abstract Introduction Invasive fungal infections (IFI) are frequent in patients admitted to the intensive care unit (ICU). The use of first-line antifungals like triazoles or echinocandins may be limited by global spread multi-drug resistance species, drug–drug interactions, low organ penetration, and some safety concerns case multi-organ failure. Liposomal amphotericin B (L-AmB) is a polyene drug with broad activity against mold yeast an acceptable profile. To outline role L-AmB treatment IFI critically ill patients, panel experts was invited draw up expert opinion paper on appropriate place therapy different clinical scenarios ICU. Methods A multidisciplinary group 16 specialists infectious disease, microbiology, pharmacology, elaborated document through multi-step approach: (1) scientific defined items wrote statements management ICU, (2) survey submitted external express agreement disagreement statements, (3) reviewed implemented final document. Results included 35 that focused epidemiology microbiological rationale systemic its potential specific Conclusion Systemic represent therapeutic choice for ICU underlying conditions, especially when agents undermined. This provide useful guide clinicians.

Language: Английский

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Isavuconazole Pharmacokinetics in Critically Ill Patients: Relationship with Clinical Effectiveness and Patient Safety

Antibiotics, Journal Year: 2024, Volume and Issue: 13(8), P. 706 - 706

Published: July 29, 2024

Isavuconazole is used to treat fungal infections. This study aims describe isavuconazole pharmacokinetics in critically ill patients and evaluate their relationship with clinical efficacy patient safety. We conducted a prospective, observational treated intravenous isavuconazole. Samples were collected at predose (Cmin), 1 h (Cmax) 12 (C50) after the last dose. The plasma concentration was determined by high-performance liquid chromatography. between microbiological outcomes safety evaluated. influence of covariates (age, sex, weight, SAPS3, creatinine, liver enzymes extracorporeal devices: continuous renal replacement therapy (CRRT) membrane oxygenation (ECMO)) analysed. Population pharmacokinetic modelling performed using NONMEN

Language: Английский

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Transplanted Heart Complicated by Intracardiac Aspergilloma With Pericardial Involvement

JACC Case Reports, Journal Year: 2024, Volume and Issue: 29(19), P. 102574 - 102574

Published: Oct. 1, 2024

Language: Английский

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