Christina Orasch1, Dominik Mertz2, Jorge Garbino3, Christian van Delden3, Stephane Emonet3, Jacques Schrenzel4, Stefan Zimmerli5, Lauro Damonti6, Konrad Mühlethaler5, Alexander Imhof7, Christian Ruef8, Jan Fehr9, Reinhard Zbinden10, Katia Boggian11, Thomas Bruderer12, Ursula Flückiger13, Anna Conen14, Nina Khanna15, Reno Frei16, Thomas Bregenzer17, Frédéric Lamoth18, Véronique Erard19, Pierre-Yves Bochud20, Thierry Calandra20, Jacques Bille21, Oscar Marchetti22. 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.
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.
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.
Authors: Andrew M Borman; Julian Muller; Jo Walsh-Quantick; Adrien Szekely; Zoe Patterson; Michael D Palmer; Mark Fraser; Elizabeth M Johnson Journal: Antimicrob Agents Chemother Date: 2019-07-25 Impact factor: 5.191
Authors: Kai-Manuel Adam; Michael Osthoff; Frédéric Lamoth; Anna Conen; Véronique Erard; Katia Boggian; Peter W Schreiber; Stefan Zimmerli; Pierre-Yves Bochud; Dionysios Neofytos; Mapi Fleury; Hans Fankhauser; Daniel Goldenberger; Konrad Mühlethaler; Arnaud Riat; Reinhard Zbinden; Andreas Kronenberg; Chantal Quiblier; Oscar Marchetti; Nina Khanna Journal: Open Forum Infect Dis Date: 2021-09-17 Impact factor: 3.835
Authors: Raja Rajeshwari; Siva Vyasam; Jolly Chandran; Sanketh Porwal; Kala Ebenezer; Muniya Thokchom; Ebor J James; Reka Karuppusami Journal: Indian J Crit Care Med Date: 2022-06