Format

Send to

Choose Destination
J Infect. 2018 May;76(5):489-495. doi: 10.1016/j.jinf.2017.12.018. Epub 2018 Jan 31.

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

Author information

1
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Infectious Diseases and Hospital Epidemiology, Hirslanden Klinik St. Anna, Lucerne, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, Basel University Hospital, Basel, Switzerland. Electronic address: Christina.Orasch@hirslanden.ch.
2
Division of Infectious Diseases, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
3
Infectious Diseases Service, Department of Medical Specialties, Geneva University Hospitals, Geneva, Switzerland.
4
Bacteriology Laboratory, Service of Laboratory Medicine, Department of Genetics & Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
5
Department of Infectious Diseases, Bern University Hospital (Inselspital), and Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
6
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Department of Infectious Diseases, Bern University Hospital (Inselspital), and Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
7
Department of Medicine, Zurich University Hospital, Zurich; Department of Medicine, Oberaargau Hospital, Langenthal, Switzerland.
8
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Hirslanden Klinik, Zürich, Switzerland.
9
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
10
Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.
11
Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital, Sankt Gallen, Switzerland.
12
Department of Bacteriology, Mycology and Parasitology, Center of Laboratory Medicine, Cantonal Hospital, Sankt Gallen, Switzerland.
13
Hirslanden Klinik, Aarau, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, Basel University Hospital, Basel, Switzerland.
14
Division of Infectious Diseases and Hospital Epidemiology, Basel University Hospital, Basel, Switzerland; Division of Infectious Diseases and Hospital Hygiene, Kantonsspital, Aarau, Switzerland.
15
Division of Infectious Diseases and Hospital Epidemiology, Basel University Hospital, Basel, Switzerland.
16
Division of Clinical Microbiology, Laboratory Medicine, Basel University Hospital, Basel, Switzerland.
17
Division of Infectious Diseases and Hospital Hygiene, Kantonsspital, Aarau, Switzerland; Klinik für Innere Medizin, Spital Lachen AG, Lachen, Switzerland.
18
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Institute of Microbiology, Department of Laboratories, Lausanne University Hospital, Lausanne, Switzerland.
19
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Clinique of Medicine, HFR-Fribourg Hospital, Fribourg, Switzerland.
20
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
21
Institute of Microbiology, Department of Laboratories, Lausanne University Hospital, Lausanne, Switzerland.
22
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Department of Medicine, Ensemble Hospitalier de la Côte, Morges, Switzerland. Electronic address: Oscar.Marchetti@chuv.ch.
23
Kantonsspital, Aarau.
24
Kantonsspital, Aarau; University Hospital, Basel.
25
University Hospital, Basel.
26
Universitätskinderspital, Basel.
27
Ospedale San Giovanni, Ente Ospedaliero Cantonale, Bellinzona.
28
University Hospital, Bern.
29
Spitalzentrum, Biel.
30
Kantonsspital, Bruderholz.
31
Kantonsspital, Chur.
32
Hôpital Cantonal, Fribourg.
33
University Hospital, Geneva.
34
Hôpital Communal, La-Chaux-de-Fonds.
35
University Hospital, Lausanne.
36
Clinique Bois-Cerf, Clinique Cécil, and Clinique La Source, Lausanne.
37
Kantonsspital, Liestal.
38
Ospedale Regionale, Ente Ospedaliero Cantonale, Locarno.
39
Ospedale Civico, Ente Ospedaliero Cantonale, Lugano.
40
Kantonsspital, Luzern.
41
Kantonsspital, Münsterlingen.
42
Kantonsspital, Olten.
43
Institut Central des Hôpitaux Valaisans, Sion.
44
Kantonsspital, Sankt Gallen.
45
Kantonsspital, Winterthur.
46
University Hospital, Zürich.
47
Stadtspital Triemli, Zürich.
48
Universitätskinderspital, Zürich.
49
Istituto Cantonale di Microbiologia, Bellinzona.
50
Viollier Microbiology Laboratories, Bienne.
51
Kantonsspital, Bruderholz; Kantospital, Liestal.
52
Clinique La Source, Lausanne.

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.

KEYWORDS:

Breakthrough; Candida; Candidemia; FUNGINOS; Fluconazole; Species; Susceptibility

PMID:
29378240
DOI:
10.1016/j.jinf.2017.12.018

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center