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Resistance of Candida spp. to antifungal drugs in the ICU: where are we now?

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Abstract

Current increases in antifungal drug resistance in Candida spp. and clinical treatment failures are of concern, as invasive candidiasis is a significant cause of mortality in intensive care units (ICUs). This trend reflects the large and expanding use of newer broad-spectrum antifungal agents, such as triazoles and echinocandins. In this review, we firstly present an overview of the mechanisms of action of the drugs and of resistance in pathogenic yeasts, subsequently focusing on recent changes in the epidemiology of antifungal resistance in ICU. Then, we emphasize the clinical impacts of these current trends. The emergence of clinical treatment failures due to resistant isolates is described. We also consider the clinical usefulness of recent advances in the interpretation of antifungal susceptibility testing and in molecular detection of the mutations underlying acquired resistance. We pay particular attention to practical issues relating to ICU patient management, taking into account the growing threat of antifungal drug resistance.

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Acknowledgments

We are grateful to Audrey Le Gouëllec for her assistance in preparing the figures.

Conflicts of interest

D. Maubon, C. Garnaud and M. Cornet received a research grant from Pfizer in 2013. T. Calandra: board membership: Pfizer; Consultancy: Pfizer, MSD; Speakers bureaus: BioMérieux, Pfizer; Development & educational presentations: MSD, Gilead Sciences (money to institution); Travel & meeting expenses: Astellas, Pfizer.

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Authors and Affiliations

  1. Parasitologie-Mycologie, Institut de Biologie et de Pathologie, CHU de Grenoble, Grenoble, France

    Danièle Maubon, Cécile Garnaud & Muriel Cornet

  2. Laboratoire TIMC-TheREx, UMR 5525 CNRS-UJF, Université Grenoble Alpes, Grenoble, France

    Danièle Maubon, Cécile Garnaud & Muriel Cornet

  3. Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

    Thierry Calandra

  4. Institute of Microbiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

    Dominique Sanglard

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  1. Danièle Maubon
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  2. Cécile Garnaud
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  3. Thierry Calandra
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  4. Dominique Sanglard
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  5. Muriel Cornet
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Correspondence to Danièle Maubon.

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Take-home message: The emergence of resistance is a warning signal triggering improvements in antifungal drug use, particularly in patients for whom the potential benefit of treatment is unproven. Practical proposals to detect and prevent the risk of clinical failure are (i) accurate assessments of prior antifungal exposure, (ii) close clinical monitoring of patients treated with antifungal drugs, (iii) routine surveillance of in vitro susceptibility testing and (iv) development of feasible methods for rapid detection of mutations.

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Maubon, D., Garnaud, C., Calandra, T. et al. Resistance of Candida spp. to antifungal drugs in the ICU: where are we now?. Intensive Care Med 40, 1241–1255 (2014). https://doi.org/10.1007/s00134-014-3404-7

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