Population genomics reveals a long-term increase in azole resistance associated with the emerging cluster AZR among <i>Candida tropicalis</i> causing invasive infections.
The study highlights a 42.3% fluconazole resistance rate in C. tropicalis, with the emerging cluster AZR posing a significant clinical challenge.
Where it sits
this study against the rest of the 5-amino-1mq corpusSummary and findings
A total of 911 Candida tropicalis isolates were collected in 2022-2023, revealing a fluconazole resistance rate of 42.3%. The study identified cluster AZR as the predominant fluconazole-resistant population, comprising 58.6% of the isolates. The findings highlight a significant increase in azole resistance associated with this emerging cluster.
Abstract
A notable increase in azole resistance among <i>Candida tropicalis</i> has been observed worldwide, particularly in the Asia-Pacific region, associated with the expansion of an emerging resistant population named cluster AZR. Here, we present up-to-date epidemiological, antifungal susceptibility and population genomic data from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study. A total of 911 <i>C. tropicalis</i> isolates causing invasive candidiasis were collected in 2022-2023, representing 16.1% of all <i>Candida</i> isolates and ranking as the third most common species. High resistance rates to fluconazole (42.3%) were observed, with 87.5% showing cross-resistance to voriconazole. Candidemia isolates showed significantly higher azole resistance than non-candidemia isolates (46.1% vs 39.2%, <i>p</i> = 0.036). Fluconazole resistance rate was higher in medical departments (55.0%) but lower in ICUs (33.7%). Longitudinal analysis demonstrated an overall upward trend in fluconazole resistance from 5.7% since 2009. Although a transient decline was observed during 2020-2021, resistance rebounded thereafter and reached a historical peak of 43.1% in 2022. Population genomic analysis of 604 isolates identified cluster AZR as the predominant fluconazole-resistant population (58.6%), and its expansion was associated with the temporal increase in azole resistance. Of note, all cluster AZR isolates harboured the <i>ERG11</i> A395 T key resistant mutation, and 98.2% had increased <i>ERG11</i> copy number. Besides, genomic analysis identified strain replacement and dual-clade mixed infection in cluster AZR-associated clinical cases. In conclusion, the high prevalence of azole resistance in <i>C. tropicalis</i> and the expansion of cluster AZR represent a significant clinical challenge and underscore the need for effective interventions.
Background
This study addresses the rising azole resistance in Candida tropicalis, particularly in the Asia-Pacific region. Prior knowledge indicated an increase in resistance rates, but the specific role of the emerging cluster AZR was unclear. Understanding the epidemiology and resistance mechanisms is crucial for managing invasive candidiasis effectively.
Methods
The study utilized data from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study, collecting 911 isolates of C. tropicalis from invasive candidiasis cases during 2022-2023. The primary outcome measured was antifungal susceptibility, specifically fluconazole resistance rates. Secondary outcomes included population genomic analysis of 604 isolates.
Results
The primary endpoint revealed a fluconazole resistance rate of 42.3% among the 911 C. tropicalis isolates. Candidemia isolates exhibited significantly higher resistance (46.1%) compared to non-candidemia isolates (39.2%), with a p-value of 0.036. The study also noted a historical peak of fluconazole resistance at 43.1% in 2022.
Interpretation
The findings indicate a concerning trend in azole resistance, particularly with the emergence of cluster AZR, which is associated with a significant proportion of fluconazole-resistant isolates. While the statistical significance is clear, the clinical implications require further investigation to determine if these resistance rates lead to poorer patient outcomes. Limitations include the potential for confounding factors such as sample size and the specific population studied.
Key findings
- 42.3% fluconazole resistance rate among 911 C. tropicalis isolates, n=911.
- 87.5% of isolates showed cross-resistance to voriconazole.
- Candidemia isolates had 46.1% azole resistance vs 39.2% in non-candidemia isolates, p=0.036.
- Fluconazole resistance rate was 55.0% in medical departments and 33.7% in ICUs.
- Fluconazole resistance increased from 5.7% in 2009 to a peak of 43.1% in 2022.
- 58.6% of isolates belonged to cluster AZR, all harboring the ERG11 A395 T mutation.
Limitations
- Not reported in abstract.