Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death

• Published in: Journal of antimicrobial chemotherapy Vol. 65; no. 5; pp. 1042 - 1051
• Main Authors: Slavin, Monica A., Sorrell, Tania C., Marriott, Deborah, Thursky, Karin A., Nguyen, Quoc, Ellis, David H., Morrissey, C. Orla, Chen, Sharon C.-A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2010; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Adults; Aged; Aged, 80 and over; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal Agents - pharmacology; Biological and medical sciences; Cancer; Candida; Candida - classification; Candida - drug effects; Candida - isolation & purification; Candida albicans; Candida glabrata; Candida krusei; Candidiasis - epidemiology; Candidiasis - microbiology; Candidiasis - mortality; Drug resistance; Drug Resistance, Fungal; Drug therapy; Female; Fluconazole - pharmacology; Fungal infections; Fungemia - epidemiology; Fungemia - microbiology; Fungemia - mortality; Human mycoses; Humans; Infectious diseases; Male; Medical sciences; Microbial Sensitivity Tests; Middle Aged; mortality; Mycological Typing Techniques; Mycoses; Mycotic sepsis; Neoplasms - complications; Pharmacology. Drug treatments; Risk Factors; susceptibility; triazoles; Young Adult; Candidiasis; Triazole; Yeast; susceptibility; Mycosis; Azole derivatives; triazoles; Fungi; Antifungal agent; Adult; Fungi Imperfecti; Human; Fluconazole; Mortality; Patient; Malignant tumor; Infection; Resistance; Sensitivity; Fungemia; Candida; Risk factor; Triazole derivatives; Isolate; Death; Cancer
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkq053

Background Candidaemia in cancer patients is associated with increasing fluconazole resistance. Models for predicting such isolates and their clinical impact are required. Methods Clinical, treatment and outcome data from a population-based candidaemia survey (2001–2004) were collected at 5 and 30 days after diagnosis. Speciation and antifungal susceptibility testing was performed. Results There were 138 candidaemia episodes (33% Candida albicans) in adults with haematological malignancies and 150 (51% C. albicans) in adults with solid organ malignancies. Thirty-nine isolates had fluconazole MICs of ≥64 mg/L and 40 had MICs of 16–32 mg/L (predominantly Candida glabrata and Candida krusei). By multivariate analysis, triazole therapy, gastrointestinal tract (GIT) surgery in the 30 days before candidaemia and age >65 years were predictive of fluconazole-resistant candidaemia. Thirty day crude mortality was 40% in haematology patients and 45% in oncology patients. Fluconazole-resistant isolates were associated with increased risk of mortality by univariate (P = 0.04) and Kaplan–Meier survival analyses. By Cox proportional hazards modelling, the strongest predictors of mortality at onset of candidaemia were invasive ventilation, elevated creatinine, intensive care unit (ICU) admission and receipt of systemic triazoles or corticosteroids in the previous 30 days. Removal of a central venous access device (CVAD) at or within 5 days of onset was associated with decreased mortality. Conclusions Risk factors for fluconazole-resistant candidaemia in adults with cancer include fluconazole/triazole exposure and GIT surgery. ICU admission, invasive ventilation, renal impairment, age >65 years and prior exposure to corticosteroids and triazoles are risk factors for death. CVAD removal reduced mortality. These findings should be integrated into surveillance and treatment algorithms.