Intensive care medicine research agenda on invasive fungal infection in critically ill patients

Abstract

Purpose:To describe concisely the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to Candida and Aspergillus infections in non-neutropenic patients in the ICU setting. Methods:A systematic review of the medical literature taking account of national and international guidelines and expert opinion. Results:Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically ill patients. Approximately 80% of IFIs are due to Candida spp. and 0.3-19% to Aspergillus spp. Recent observations emphasize the necessity of building a worldwide sentinel network to monitor the emergence of new fungal species and changes in susceptibility. Robust data on the attributable mortality are essential for the design of clinical studies with mortality endpoints. Although early antifungal therapy for Candida has been recommended in patients with risk factors, sepsis of unknown cause, and positive Candida serum biomarkers [β-1 → 3-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA)], its usefulness and influence on outcome need to be confirmed. Future studies may specifically address the optimal diagnostic and therapeutic strategies for patients with abdominal candidiasis. Better knowledge of the pharmacokinetics of antifungal molecules and tissue penetration is a key issue for intensivists. Regarding invasive aspergillosis, further investigation is needed to determine its incidence in the ICU, its relationship with influenza outbreaks, the clinical impact of rapid diagnosis, and the significance of combination treatment. Conclusions:Fundamental questions regarding IFI have to be addressed over the next decade. The clinical studies described in this research agenda should provide a template and set priorities for the clinical investigations that need to be performed.

Candida bloodstream infections in Serbia: First multicentre report of a national prospective observational survey in intensive care units

“…The overall Candida BSI mortality rate in this study was similar to other European hospital‐based studies, but somewhat higher in our adult subjects, which was intriguing, since it was well documented that the highest Candida BSI associated mortality is usually observed in the LBW population. This finding can be explained by the fact that half of adult patients who died in the course of Candida BSI did not receive antifungal therapy.…”

“…Candida ( C .) bloodstream infections (BSI) or invasive candidiasis (IC) has a significant impact on morbidity, mortality, the length of hospital stay and costs, especially for patients in the intensive care units (ICUs) . The overall crude mortality rate in these patients reaches up to 40%‐71%, and overall incidence ranges from 1 to ~10 cases per 1000 ICU admissions …”

“…Various surveys conducted in Europe have underscored the fact that average 45% of all IC episodes arise in ICU patients . Moreover, about 80% of invasive fungal infections (IFIs) are due to Candida species, which is the third most common isolated microorganism worldwide, accounting for 17% of all infections in ICUs, associated with high hospital mortality rates and spending resources …”

What Is the Most Recent Evidence on the Prevention and Early Treatment of Invasive Fungal Infections in Nonneutropenic Critically Ill Patients?

“…Physicians should evaluate case-by-case risks and benefits of antifungal treatment after considering treatment timing, risk factors, local microbiological epidemiology, costs, available biomarkers, and diagnostic microbiological assays in their institutions (36,37). Future research should evaluate the effectiveness and applicability of combined strategies using several methods to correctly select patients, who may benefit from timely and adequate untargeted antifungal treatment.…”

Biomarker-guided antifungal therapy in patients with suspected invasive candidiasis: Ready for prime time?

“…As reported recently, 28-day crude mortality rates remain high in those patients, around 40% [2]. Delayed antifungal therapy (AFT) is associated with significant increase in hospital mortality and health care costs and is mainly linked to late diagnosis [3,4]. Accordingly, blood cultures are positive in only 50-70% of cases of candidemia and time to positivity is longer than in bacteremia [2].…”