Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study.
J Infect
; 76(5): 489-495, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29378240
ABSTRACT
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:
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.RESULTS:
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.CONCLUSIONS:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Candida
/
Fluconazol
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Farmacorresistência Fúngica
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Candidemia
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Antifúngicos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article