Podcast: Antifungal agents for preventing fungal infections in critically ill adults and children with a normal number of neutrophils in the blood

Invasive fungal infections are important causes of morbidity and mortality among critically ill patients, and an updated Cochrane Review in January 2016 examines the effects of antifungal agents to prevent these infections. The lead author, Andrea Cortegiani, from the University of Palermo in Italy summarises the latest evidence in this podcast.

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John: Invasive fungal infections are important causes of morbidity and mortality among critically ill patients, and an updated Cochrane Review in January 2016 examines the effects of antifungal agents to prevent these. The lead author, Andrea Cortegiani, from the University of Palermo in Italy summarises the latest evidence in this podcast.

Andrea: When a critically ill patient has a fungal infection, it’s vital to start antifungal therapy as early as possible to reduce the risk of them dying from the infection. However, waiting for laboratory confirmation of the infection can take a long time. Therefore, alternative strategies for starting antifungal therapy in patients without proven microbiological evidence of fungal infections have been developed. These strategies are globally defined as untargeted antifungal treatments and encompass prophylaxis, pre-emptive and empiric treatment. We examine their effects in this review which was originally published in 2006, and this 2016 update provides moderate quality evidence that untargeted antifungal treatment is not associated with a significant reduction in total (all-cause) mortality among critically ill, non-neutropenic adults and children when compared to no antifungal treatment or a placebo.
We investigated the effects of untargeted treatment with any antifungal drug compared to placebo or no antifungal or any other antifungal drug in non-neutropenic, critically ill adults and children. We have now found 22 randomized trials for a total of nearly 2800 participants, addigin 10 trials to the 12 that were in the original review. Eleven trials compared fluconazole against placebo or no antifungal treatment, three trials compared ketoconazole versus placebo; while only one or two trials had assessed other drugs, including amphotericin B, anidulafungin, caspofungin, clotrimazole, ketoconazole, micafungin and nystatin. The trials included a variety of patients, including both men and women, a wide range of ages and those with different severities of critical illness.
In summary, alongside the moderate quality evidence of the lack of a benefit for total (all-cause) mortality, we found low quality evidence that untargeted antifungal treatment may be associated with a reduction of invasive fungal infections. Amidst these uncertainties, further high-quality randomised trials are needed, especially for prophylaxis with more recent and less studied drugs, including echinocandis, and for strategies such as pre-emptive antifungal treatment.

John: If you’d like to read more about the current evidence, and to watch for further updates of the review, visit Cochrane Library dot com and search for 'fungal infections and critically ill patients'.

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