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Antimicrobial Agents and Chemotherapy, July 2004, p. 2471-2476, Vol. 48, No. 7
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.7.2471-2476.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Impact of Fluconazole Prophylaxis on Cortisol Levels in Critically Ill Surgical Patients

Division of Infectious Diseases,¹ Division of Clinical Pharmacology,² Department of Surgery,³ Division of Oncology Biostatistics,⁴ Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland⁵

Received 2 December 2003/ Returned for modification 30 December 2003/ Accepted 27 February 2004

Fluconazole is widely used in the intensive care unit for prevention and treatment of fungal infections. Case reports have described an association between fluconazole and adrenal dysfunction, an important cause of morbidity and mortality in critically ill patients. We sought to determine whether 400 mg of fluconazole per day administered to critically ill surgical patients was associated with a reduction in cortisol levels. Cortisol levels were measured in stored plasma specimens drawn from 154 critically ill surgical patients randomized in 1998-1999 to receive fluconazole or placebo for the prevention of candidiasis. The primary outcome measure was the median plasma cortisol level 1 day after study drug initiation (MPCL). Secondary outcomes were adrenal dysfunction, defined as an MPCL of <15 µg/dl, changes in cortisol levels over time, and mortality. The median MPCL was 15.75 µg/dl (interquartile range [IQR], 11.65 to 21.33 µg/dl) in 79 patients randomized to fluconazole and 16.71 µg/dl (IQR, 11.67 to 23.00 µg/dl) in 75 patients randomized to placebo (P = 0.52). Patients randomized to fluconazole did not have significantly increased odds of adrenal dysfunction compared to patients randomized to placebo (odds ratio, 0.98; 95% confidence interval, 0.48 to 2.01). Randomization to fluconazole was not associated with a significant difference in cortisol level changes over time. Mortality was not different between patients with and without adrenal dysfunction, nor was it different between patients with adrenal dysfunction who were randomized to fluconazole and those randomized to placebo. Fluconazole prophylaxis in this population of critically ill surgical patients did not result in significant adrenal dysfunction.

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• Riedl, M., Maier, C., Zettinig, G., Nowotny, P., Schima, W., Luger, A. (2006). Long term control of hypercortisolism with fluconazole: case report and in vitro studies.. Eur J Endocrinol 154: 519-524 [Abstract] [Full Text]  
• Salvatori, R. (2005). Adrenal Insufficiency. JAMA 294: 2481-2488 [Abstract] [Full Text]