Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study.
Détails
ID Serval
serval:BIB_AB78279BDFD7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study.
Périodique
The Journal of infection
Collaborateur⸱rice⸱s
Fungal Infection Network of Switzerland (FUNGINOS)
Contributeur⸱rice⸱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
Statut éditorial
Publié
Date de publication
05/2018
Peer-reviewed
Oui
Volume
76
Numéro
5
Pages
489-495
Langue
anglais
Notes
Publication types: Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Création de la notice
01/02/2018 18:28
Dernière modification de la notice
24/09/2019 5:11
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