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Cross-resistance between voriconazole and fluconazole for non-albicans Candida infection: a case-case-control study


Cross-resistance (CR) between voriconazole and fluconazole for non-albicans Candida (NAC) species is not uncommon, but little is known about the risk factors and clinical consequences associated with this resistance phenotype. A case-case-control study was performed at a university-affiliated hospital in China between November 2012 and April 2016. The two case groups respectively comprised patients with a mono-resistance (MR) NAC infection (fluconazole or voriconazole resistance) and patients with a CR NAC infection (fluconazole and voriconazole resistance). Patients with a no-resistance (NR) NAC infection were included as the control group. Models were adjusted for demographic and clinical risk factors, and the risk of resistance associated with exposure to specific antibiotics or non-antibiotics were assessed. Of 259 episodes, 33 (12.7%) and 27 (10.4%) were identified as MR and CR NAC infections, respectively. The broad use of azoles was strongly associated with the emergence of MR and CR NAC infections (adjusted odds ratio [95% confidence interval] = 2.69 [1.10–6.58] and 2.53 [1.02–6.28], respectively). The time at risk (1.02 [1.00–1.03]) with 12 days as a breakpoint was also an independent risk factor for CR NAC infection. The number of species associated with a high minimum inhibitory concentration (≥128 μg/mL) of fluconazole was higher for CR NAC infections than for MR NAC infections. Different resistance phenotypes (CR vs. MR vs. NR) were associated with all-cause mortality rates. These findings indicate a worrisome propensity of CR NAC infections and emphasize the need for strict antifungal stewardship.

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The authors acknowledge the Junhui Liu for isolation and identification of isolates.

Author information

Correspondence to Y. Dong.

Ethics declarations


This work was supported by internal funding (i.e. the National Natural Science Foundation of China [No. 81672954], the Natural Science Foundation of Shaanxi Province [No. 2016JM8015], and the Clinical Research Subject of The First Affiliated Hospital of Xi’an Jiaotong University [No. XJTU1AHCR2014–002]).

Competing interests

On behalf of all authors, the corresponding author states that there is no competing interest.

Ethical approval

This study protocol was approved by the Hospital Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University.

Informed consent

Informed consent was not required from the study subjects.

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Wang, Y., Yang, Q., Chen, L. et al. Cross-resistance between voriconazole and fluconazole for non-albicans Candida infection: a case-case-control study. Eur J Clin Microbiol Infect Dis 36, 2117–2126 (2017).

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