ICU Patients’ Antibiotic Exposure and Triazole-Resistance in Invasive Candidiasis: Parallel Analysis of Aggregated and Individual Data

Yan Wang, Ying Zhang, Mater Health, Samantha A. Hollingworth, Mieke L. Van Driel, Lu Cao, Xue Wang, Yalin Dong*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)
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Background: The relationship between antibiotic use and the incidence of triazole-resistant phenotypes of invasive candidiasis (IC) in critically ill patients is unclear. Different methodologies on determining this relationship may yield different results. 

Methods: A retrospective multicenter observational analysis was conducted to investigate exposure to antibiotics and the incidence of non-duplicate clinical isolates of Candida spp. resistant to fluconazole, voriconazole, or both during November 2013 to April 2018, using two different methodologies: group-level (time-series analysis) and individual-patient-level (regression analysis and propensity-score adjusting). 

Results: Of 393 identified Candida spp. from 388 critically ill patients, there were three phenotypes of IC identified: fluconazole-resistance (FR, 63, 16.0%); voriconazole-resistance (VR, 46, 11.7%); and cross-resistance between fluconazole and voriconazole (CR, 32, 8.1%). Exposure to several antibacterial agents with activity against the anaerobic gastrointestinal flora, especially third-generation cefalosporins (mainly cefoperazone/sulbactam and ceftriaxone), but not triazoles, have an immediate effect (time lag = 0) on subsequent ICU-acquired triazole-resistant IC in the group-level (p < 0.05). When the same patient database was analyzed at the individual-patient-level, we found that exposure to many antifungal agents was significantly associated with triazole-resistance (fluconazole [adjusted odds ratio (aOR) = 2.73] or caspofungin [aOR = 11.32] on FR, voriconazole [aOR = 2.87] on CR). Compared to the mono-triazole-resistant phenotype, CR IC has worse clinical outcomes (14-days mortality) and a higher level of resistance. 

Conclusion: Group-level and individual-patient-level analyses of antibiotic-use-versus-resistance relations yielded distinct but valuable results. Antibacterials with antianaerobic activity and antifungals might have “indirect” and “direct” effect on triazole-resistant IC, respectively.

Original languageEnglish
Article number586893
JournalFrontiers in Pharmacology
Publication statusPublished - 22 Mar 2021


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