Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study.
Details
Serval ID
serval:BIB_AB78279BDFD7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study.
Journal
The Journal of infection
Working group(s)
Fungal Infection Network of Switzerland (FUNGINOS)
Contributor(s)
Bregenzer T., Conen A., Flückiger U., Khanna N., Orasch C., Heininger U., Franciolli M., Damonti L., Zimmerli S., Rothen M., Zellweger C., Rothen M., Tarr P., Fleisch F., Chuard C., Erard V., Emonet S., Garbino J., van Delden C., Genne D., Bochud P.Y., Calandra T., Damonti L., Erard V., Lamoth F., Marchetti O., Orasch C., Chave J.P., Graber P., Monotti R., Bernasconi E., Rossi M., Krause M., Piso R.J., Bally F., Troillet N., Boggian K., Eich G., Gubler J., Fehr J., Imhof A., Ruef C., Eich G., Gubler J., Berger C., Fankhauser H., Heinzer I., Frei R., Hertel R., Dolina M., Petrini O., Dubuis O., Mühlethaler K., Graf S., Risch M., Ritzler E., Fracheboud D., Rohner P., Schrenzel J., Lienhardt R., Bille J., Lamoth F., Andreutti-Zaugg C., Gallusser A., Graf S., Pfyffer G., Herzog K., Schibli U., Tissière L., Bruderer T., Schultze D., Zbinden R.
ISSN
1532-2742 (Electronic)
ISSN-L
0163-4453
Publication state
Published
Issued date
05/2018
Peer-reviewed
Oui
Volume
76
Number
5
Pages
489-495
Language
english
Notes
Publication types: Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
A 3-year prospective study was conducted in 567 consecutive candidemias. Species identification and antifungal susceptibility testing (CLSI) were performed in the FUNGINOS reference laboratory. Data were analyzed according to STROBE criteria.
43/576 (8%) BTC occurred: 37/43 (86%) on fluconazole (28 prophylaxis, median 200 mg/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), and 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 4 mg/l vs. 0.25 mg/l (p < 0.001). Ten-day fluconazole exposure predicted non-susceptible BTC with 73% accuracy.
Outcomes of BTC and non-BTC were 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.
A 3-year prospective study was conducted in 567 consecutive candidemias. Species identification and antifungal susceptibility testing (CLSI) were performed in the FUNGINOS reference laboratory. Data were analyzed according to STROBE criteria.
43/576 (8%) BTC occurred: 37/43 (86%) on fluconazole (28 prophylaxis, median 200 mg/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), and 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 4 mg/l vs. 0.25 mg/l (p < 0.001). Ten-day fluconazole exposure predicted non-susceptible BTC with 73% accuracy.
Outcomes of BTC and non-BTC were 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.
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents/administration & dosage, Candida/drug effects, Candidemia/microbiology, Candidemia/mortality, Candidemia/prevention & control, Child, Child, Preschool, Drug Resistance, Fungal, Epidemiological Monitoring, Female, Fluconazole/administration & dosage, Humans, Infant, Infant, Newborn, Male, Microbial Sensitivity Tests, Middle Aged, Prospective Studies, Young Adult, Breakthrough, Candida, Candidemia, FUNGINOS, Fluconazole, Species, Susceptibility
Pubmed
Web of science
Create date
01/02/2018 18:28
Last modification date
24/09/2019 5:11
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