Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study

Publication

Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study

Journal Paper/Review - Jan 26, 2018

Orasch Christina, Fluckiger Ursula, Conen Anna, Khanna Nina, Frei Reno, Bregenzer Thomas, Lamoth Frédéric, Erard Véronique, Bochud Pierre-Yves, Calandra Thierry, Bille Jacques, Marchetti Oscar, Bruderer Thomas, Boggian Katia, Zbinden Reinhard, Mertz Dominik, Garbino Jorge, Van Delden Christian, Emonet Stephane, Schrenzel Jacques, Zimmerli Stefan, Damonti Lauro, Mühlethaler Konrad, Imhof Alexander, Ruef Christian, Fehr Jan, Fungal Infection Network of Switzerland (FUNGINOS)

Citation

Orasch C, Fluckiger U, Conen A, Khanna N, Frei R, Bregenzer T, Lamoth F, Erard V, Bochud P, Calandra T, Bille J, Marchetti O, Bruderer T, Boggian K, Zbinden R, Mertz D, Garbino J, Van Delden C, Emonet S, Schrenzel J, Zimmerli S, Damonti L, Mühlethaler K, Imhof A, Ruef C, Fehr J, Fungal Infection Network of Switzerland (FUNGINOS). Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study. J Infect 2018

Type

Journal Paper/Review (English)

Journal

J Infect 2018

Publication Date

Jan 26, 2018

Issn Electronic

1532-2742

Brief description/objective

OBJECTIVES
Breakthrough candidemia (BTC) on fluconazole was associated with non-susceptible Candida spp. and increased mortality. This nationwide FUNGINOS study analyzed clinical and mycological BTC characteristics.

METHODS
3-year prospective study in 567 consecutive candidemias. Species identification and susceptibility testing (CLSI) in reference laboratory. Data analysis according to STROBE criteria.

RESULTS
43/576 (8%) BTC were studied: 37/43 (86%) on fluconazole (28 prophylaxis, median 200mg/day). 21% BTC vs. 23% non-BTC presented severe sepsis/septic shock. Overall mortality was 34% vs. 32%. BTC was associated with gastrointestinal mucositis (multivariate OR 5.25, 95%CI 2.23-12.40, p<0.001) and graft-versus-host-disease (6.25, 1.00-38.87, p=0.05), immunosuppression (2.42, 1.03-5.68, p=0.043), parenteral nutrition (2.87, 1.44-5.71, p=0.003). Non-albicans Candida were isolated in 58% BTC vs. 35% non-BTC (p=0.005). 63% of 16 BTC occurring after 10-day fluconazole were non-susceptible (Candida glabrata, Candida krusei, Candida norvegensis) vs. 19% of 21 BTC (C. glabrata) following shorter exposure (7.10, 1.60-31.30, p=0.007). Median fluconazole MIC was 4mg/l vs. 0.25mg/l (p<0.001). Ten-day fluconazole exposure predicted non-susceptible BTC with 73% accuracy.

CONCLUSIONS
Outcome of BTC and non-BTC was similar. Fluconazole non-susceptible BTC occurred in three out of four cases after prolonged low-dose prophylaxis. This implies reassessment of prophylaxis duration and rapid de-escalation of empirical therapy in BTC after short fluconazole exposure.