ABSTRACT
Invasive candidiasis (IC) is a severe infection primarily affecting immunocompromised patients and is associated with high mortality and substantial hospital costs. Accurate regional data on epidemiology and antifungal resistance of IC are crucial for effective clinical management. The China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study is a laboratory-based multicenter study initiated in August 2009. This report presented updated data from August 2017 to December 2021, involving 76 hospitals across 28 provincial regions in China, and included a 12-year longitudinal analysis. Isolates from patients with IC were assigned to species level by matrix-assisted laser desorption ionization-time of flight mass spectrometry and internal transcribed spacer rDNA sequencing. Susceptibility testing was performed for nine antifungal agents using the broth microdilution method. A total of 11,679 Candida isolates were collected. Candida albicans was the most common Candida species (46.0%), followed by Candida tropicalis (17.6%), Candida parapsilosis sensu stricto (15.6%), and Candida glabrata sensu stricto (11.2%). Antifungal resistance rates showed notable variations among different Candida species, with the highest azole resistance observed in C. tropicalis isolates causing candidemia (42.5% to fluconazole and 38.9% to voriconazole). Cross- and multi-drug resistance to azoles and echinocandins was observed in all predominant Candida species. The species distribution of major Candida pathogens causing IC remained stable in China, while antifungal resistance increased, especially among non-albicans Candida species. Enhanced surveillance, accurate species identification, and strengthened antifungal stewardship are needed to address the growing challenge of antifungal resistance.
KEYWORDS: invasive fungal diseases, antifungal resistance, surveillance, candidiasis
INTRODUCTION
Invasive candidiasis (IC) is a severe infection that mainly affects immunocompromised patients, which is associated with high mortality and substantial additional hospital costs (1). Globally, the incidence of IC is increasing (2). Concurrently, the prevalence of antifungal resistance, both in Candida albicans and non-albicans species, as well as multi-drug resistance (e.g., in Candida auris), is also on the rise (3, 4). These trends are further complicated by the limited availability of effective antifungal therapeutic options, highlighting the urgent need for improved diagnostics, enhanced antifungal stewardship, and the development of novel antifungal agents (5). Given these challenges, accurate regional data on the epidemiology of IC and corresponding antifungal resistance patterns are crucial for guiding clinical practice and developing effective management strategies (6).
The distribution of Candida species causing IC and antifungal resistance varies significantly across different regions and demographic groups (7). The China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study was a nationwide surveillance program initiated in 2009 (8). In previous studies, our team has reported the data from the first 5-year period (CHIF-NET 2010–2014) (9) and the subsequent 3-year period (CHIF-NET 2015–2017) (10). In this study, we present the most recent 4-year surveillance results on IC, covering the surveillance period CHIF-NET 2018–2021, to provide an updated view of the trends and characteristics of IC in China.
MATERIALS AND METHODS
Study design
The CHIF-NET study is a laboratory-based multicenter study of invasive yeast infections, which was initiated in August 2009 (8), and the inclusion criteria for isolates have been described previously (8–10). Of note, before CHIF-NET 2018, each surveillance year spanned from August of the preceding year to July of the current year (e.g., CHIF-NET 2010 covered August 2009 to July 2010). To facilitate data management and analysis, the surveillance period was extended in CHIF-NET 2018 to cover August 2017 through December 2018. Thereafter, each surveillance year was aligned with the calendar year (January–December). Accordingly, the data set analyzed in this study spans from August 2017 to December 2021, covering a total period of 4 years and 4 months. A total of 76 hospitals participated in the study during this period (with 45–55 hospitals included in each surveillance year), covering 28 provincial administrative regions of China. Each surveillance year, isolates from eligible patients with invasive fungal diseases were forwarded to the central laboratory (Department of Laboratory Medicine, Peking Union Medical College Hospital, Beijing, China) for confirmative species identification and antifungal susceptibility testing. Related processing procedures were as previously described (10).
Species identification
All Candida isolates were identified to the species level in the central laboratory by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using Autof MS 1000 (Autobio Diagnostics, Zhengzhou, China) or Vitek MS (bioMérieux, Marcy l’Etoile, France) system.
For any isolates belonging to closely related yeast species complexes—including the C. albicans species complex (C. albicans and Candida dubliniensis), the Candida parapsilosis species complex (C. parapsilosis sensu stricto, Candida metapsilosis, Candida orthopsilosis, and Lodderomyces elongisporus), the Candida glabrata species complex (C. glabrata sensu stricto, Candida nivariensis, and Candida bracarensis), and the Candida haemulonii-C. auris species complex (C. haemulonii sensu stricto, Candida duobushaemulonii, Candida pseudohaemulonii, and C. auris), as well as for isolates with low-confidence MALDI-TOF MS results—sequencing of the internal transcribed spacer (ITS) rDNA region was performed for confirmatory species identification. The criteria for identification and discrepant analysis were as previously described (11).
Antifungal susceptibility testing
Susceptibility testing was performed against nine antifungal agents using in-house-prepared 96-well microdilution plates: four azoles, that is, fluconazole (FZ), voriconazole (VOR), itraconazole (IZ), and posaconazole (PZ); three echinocandins, that is, caspofungin (CAS), micafungin (MF), and anidulafungin (AND); as well as 5-flucytosine (5-FC), and amphotericin B (AMB). The operating procedure and result interpretation were referred to the Clinical and Laboratory Standards Institute (CLSI) M27M44SED3 and M57SED4 documents (12, 13). For C. albicans, clinical breakpoints (CBPs) were applied to FZ, VOR, CAS, MF, and AND, and epidemiological cutoff values (ECVs) were used for PZ and AMB. For C. parapsilosis sensu stricto, C. tropicalis, and Candida krusei, CBPs were applied to FZ (except for C. krusei, which is intrinsically resistant to FZ), VOR, CAS, MF, and AND, and ECVs were used for IZ, PZ, and AMB. For C. glabrata sensu stricto, CBPs were applied to FZ, CAS, MF, and AND, whereas ECVs were used for VOR, IZ, PZ, and AMB. Quality control was performed using C. krusei ATCC 6258 and C. parapsilosis ATCC 22019. Isolates that were resistant (R) or non-wild-type (NWT) to ≥2 agents within the same antifungal class were considered cross-resistant, whereas isolates that were R or NWT to agents from at least two of the following classes—azoles, echinocandins, and amphotericin B—were considered multi-drug resistant (5-FC was not included due to the lack of CBPs or ECVs).
Statistical analysis
Statistical analyses and data visualization were performed using R (Version 4.2.1) (https://cran.r-project.org). Comparisons of categorical variables were performed using the χ² test or Fisher’s exact test, as appropriate. A P-value <0.05 was considered statistically significant.
RESULTS
Overall species distribution
A total of 11,679 non-repetitive Candida isolates were collected in CHIF-NET 2018–2021 (Table 1), which accounted for 90.2% of all 12,954 yeast isolates identified during this period, and 37.0% (4,325/11,679) of the Candida isolates were isolated from female patients. The age of patients ranged from 0 to 104 years old (median: 60, interquartile range [IQR]: 24–71). Among all Candida isolates, C. albicans was the most common species overall and within each surveillance year, accounting for 46.0% (5,368/11,679) of the isolates in total. C. tropicalis and C. parapsilosis sensu stricto were the second and third most common species, accounting for 17.6% (2,054/11,679) and 15.6% (1,821/11,679) of the collection, followed by C. glabrata sensu stricto (1,306/11,679, 11.2%). Within the C. haemulonii–C. auris species complex (n = 34), which is of global concern, C. haemulonii sensu stricto was the most common (n = 21), followed by C. duobushaemulonii (n = 7), C. auris (n = 5), and C. pseudohaemulonii (n = 1). Other Candida species with a prevalence of >1% included C. metapsilosis (235/11,679, 2.0%), C. krusei (213/11,679, 1.8%), C. orthopsilosis (165/11,679, 1.4%), C. guilliermondii (149/11,679, 1.3%), and C. lusitaniae (118/11,679, 1.0%), and the rest rare Candida species added up to 1.8% (216/11,679).
TABLE 1.
Distribution of Candida species in CHIF-NET 2018–2021
| Species/species complex | Overall | CHIF-NET 2018 |
CHIF-NET 2019 |
CHIF-NET 2020 |
CHIF-NET 2021 |
|---|---|---|---|---|---|
| C. albicans species complex | 5,374 (46.0%) | 1,557 (43.2%) | 1,289 (48.7%) | 1,068 (47.7%) | 1,460 (45.8%) |
| C. albicans | 5,368 (46.0%) | 1,556 (43.2%) | 1,287 (48.6%) | 1,067 (47.7%) | 1,458 (45.7%) |
| C. dubliniensis | 6 (0.1%) | 1 (0.0%) | 2 (0.1%) | 1 (0.0%) | 2 (0.1%) |
| C. parapsilosis species complex | 2,255 (19.3%) | 695 (19.3%) | 448 (16.9%) | 441 (19.7%) | 671 (21.1%) |
| C. parapsilosis sensu stricto | 1,821 (15.6%) | 556 (15.4%) | 338 (12.8%) | 363 (16.2%) | 564 (17.7%) |
| C. metapsilosis | 235 (2.0%) | 73 (2.0%) | 58 (2.2%) | 44 (2.0%) | 60 (1.9%) |
| C. orthopsilosis | 165 (1.4%) | 53 (1.5%) | 46 (1.7%) | 29 (1.3%) | 37 (1.2%) |
| Lodderomyces elongisporus | 34 (0.3%) | 13 (0.4%) | 6 (0.2%) | 5 (0.2%) | 10 (0.3%) |
| C. tropicalis | 2,054 (17.6%) | 731 (20.3%) | 429 (16.2%) | 393 (17.6%) | 501 (15.7%) |
| C. glabrata species complex | 1,320 (11.3%) | 415 (11.5%) | 318 (12.0%) | 226 (10.1%) | 361 (11.3%) |
| C. glabrata sensu stricto | 1,306 (11.2%) | 412 (11.4%) | 317 (12.0%) | 221 (9.9%) | 356 (11.2%) |
| C. nivariensis | 11 (0.1%) | 2 (0.1%) | 1 (0.0%) | 4 (0.2%) | 4 (0.1%) |
| C. bracarensis | 3 (0.0%) | 1 (0.0%) | 0 (0.0%) | 1 (0.0%) | 1 (0.0%) |
| C. krusei | 213 (1.8%) | 69 (1.9%) | 63 (2.4%) | 28 (1.3%) | 53 (1.7%) |
| C. guilliermondii | 149 (1.3%) | 32 (0.9%) | 40 (1.5%) | 28 (1.3%) | 49 (1.5%) |
| C. lusitaniae | 118 (1.0%) | 21 (0.6%) | 31 (1.2%) | 22 (1.0%) | 44 (1.4%) |
| C. pelliculosa | 53 (0.5%) | 33 (0.9%) | 6 (0.2%) | 7 (0.3%) | 7 (0.2%) |
| C. haemulonii-C. auris species complex | 34 (0.3%) | 18 (0.5%) | 6 (0.2%) | 6 (0.3%) | 4 (0.1%) |
| C. haemulonii sensu stricto | 21 (0.2%) | 10 (0.3%) | 5 (0.2%) | 4 (0.2%) | 2 (0.1%) |
| C. duobushaemulonii | 7 (0.1%) | 3 (0.1%) | 1 (0.0%) | 1 (0.0%) | 2 (0.1%) |
| C. auris | 5 (0.0%) | 5 (0.1%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| C. pseudohaemulonii | 1 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (0.0%) | 0 (0.0%) |
| C. fabianii | 27 (0.2%) | 7 (0.2%) | 8 (0.3%) | 3 (0.1%) | 9 (0.3%) |
| C. norvegensis | 27 (0.2%) | 8 (0.2%) | 4 (0.2%) | 7 (0.3%) | 8 (0.3%) |
| C. rugosa | 13 (0.1%) | 6 (0.2%) | 0 (0.0%) | 2 (0.1%) | 5 (0.2%) |
| C. kefyr | 9 (0.1%) | 2 (0.1%) | 2 (0.1%) | 1 (0.0%) | 4 (0.1%) |
| Other Candida species | 33 (0.3%) | 12 (0.3%) | 4 (0.2%) | 6 (0.3%) | 11 (0.3%) |
| Overall | 11,679 (100.0%) |
3,606 (100.0%) |
2,648 (100.0%) |
2,238 (100.0%) |
3,187 (100.0%) |
Hospital departments and specimen types
This study included not only Candida isolates from bloodstream infections (4,686/11,679, 40.1%) but also those causing other types of IC. Among non-candidemia isolates, the most common source was ascites (2,062/11,679, 17.7%), followed by bronchoalveolar lavage fluid (BALF, 896/11,679, 7.7%), bile (778/11,679, 6.7%), drainage fluid (756/11,679, 6.5%), and pus (689/11,679, 5.9%). C. albicans was the most frequently isolated species among most specimen types, although its prevalence varied by source (Fig. 1a). In candidemia cases, a lower proportion of C. albicans (1,582/4,686, 33.8%) and a higher proportion of C. parapsilosis sensu stricto (1,030/4,686, 22.0%) were recognized. Relatively low proportions of C. albicans are also observed in dialysate (15/90, 16.7%).
Fig 1.
Overall species distribution and antifungal susceptibility profiles in all invasive candidiasis cases. (a) Species distribution by specimen type. The total number of each specimen type is indicated at the bottom of the bar chart. (b) Antifungal susceptibility profile of C. albicans, (c) C. parapsilosis, (d) C. tropicalis, (e) C. glabrata, and (f) C. krusei. Abbreviations: BALF, bronchoalveolar lavage fluid; S, susceptible; SDD, susceptible-dose dependent; I, intermediate; R, resistant; WT, wild type; NWT, non-wild type.
Figure 2a summarizes the distribution of Candida species across different clinical settings. Of all 11,679 isolates, 93.6% were from hospitalized patients, with the majority originating from intensive care units (ICUs, 33.7%), surgical wards (33.3%), medical wards (20.8%), and other hospitalized patients (5.8%). The remaining isolates were from outpatient (1.5%) or emergency (4.9%) settings. C. albicans was the most common species in all departments. However, C. tropicalis exhibited a relatively higher isolation rate in medical wards (627/2,430, 25.8%, P < 0.001), and the isolation rate of C. albicans in medical wards was the lowest (964/2,430, 39.7%) compared to their distribution in other departments (P < 0.001).
Fig 2.
Distribution and antifungal susceptibility of the most prevalent Candida species in candidemia cases. (a) Ward distribution of major Candida species among all invasive candidiasis cases (as references for comparison). (b) Ward distribution of major Candida species in candidemia cases. (c) Age group distribution of major Candida species in candidemia cases. (d) Fluconazole susceptibility profile of major Candida species in candidemia. (e) Voriconazole susceptibility profile of major Candida species in candidemia. (f) Caspofungin susceptibility profile of major Candida species in candidemia. Abbreviations: ER, emergency room.
In vitro susceptibility to azoles
The resistance rates, MIC50, MIC90, and geometric mean (GM) MIC values for all Candida species over the 4-year period are provided in the Supplementary Information, and the antifungal susceptibility profiles of predominant Candida species are shown in Fig. 1b through f. The four species within the C. parapsilosis species complex exhibited distinct azole susceptibility profiles. Of note, the resistance rates for FZ in C. metapsilosis and C. orthopsilosis increased over the 4-year period: for C. orthopsilosis, the FZ resistance rate increased from 35.8% in the first year to 56.8%–62.1% in the third and fourth years; and for C. metapsilosis, the FZ resistance rate increased from 3.4%–4.5% in the first 3 years to 10.0% in the fourth year. In contrast, FZ resistance rates in C. albicans and C. tropicalis remained relatively stable over the study period: consistently low in C. albicans (<5%) and persistently high in C. tropicalis (>30%). For C. glabrata sensu stricto, FZ resistance increased from 6.3% (26/412) in CHIF-NET 2018 to 18.0% (64/356) in CHIF-NET 2021. Compared with FZ, VOR generally exhibited lower resistance among major Candida species. Specifically, resistance to VOR was markedly lower than to FZ in C. albicans (1.7% vs. 3.5%, P < 0.001) and C. parapsilosis sensu stricto (1.6% vs. 5.9%, P < 0.001). Of C. krusei isolates, which were intrinsically resistant to FZ, 1.9% (4/213) were VOR-resistant and 8.0% (17/213) were intermediate. Besides, C. tropicalis showed similar resistance rates to VOR and FZ (29.1% vs. 32.6%, P = 0.015). Moreover, C. glabrata sensu stricto isolates exhibited high NWT rates to VOR, ranging from 40.3% to 57.4% over the 4-year period. For IZ, almost all (>99%) C. parapsilosis sensu stricto and C. krusei isolates were of WT phenotypes. In addition, no C. krusei isolates were NWT to IZ. The prevalence of C. glabrata sensu stricto isolates of NWT phenotype to IZ stayed below 10%, but rose gradually from 3.4% (14/412) in CHIF-NET 2018 to 7.3% (26/356) in CHIF-NET 2021. C. tropicalis showed the highest NWT rates to IZ, exceeding 20% in CHIF-NET 2019 (98/429, 22.8%) and subsequently declining to 13.7% (54/393) in CHIF-NET 2020. In comparison, the NWT rates against PZ were high among all common Candida species except for C. parapsilosis sensu stricto, which was around 5% in C. albicans and C. krusei, 65% in C. tropicalis, and >30% in C. glabrata sensu stricto. Only five C. auris isolates were identified in CHIF-NET 2018, all of which originated from the same hospital and were 100% resistant to FZ.
In vitro susceptibility to echinocandins, amphotericin B, and 5-flucytosine
For the echinocandins, susceptibility testing was performed for three drugs: CAS, MF, and AND. The results are presented in Fig. 1b through f. All three echinocandin agents demonstrated good in vitro activity against common Candida species. C. albicans and C. parapsilosis sensu stricto were ≥99% susceptible to CAS, MF, and AND. Over 98% of C. tropicalis isolates were susceptible to CAS and MF, and the resistance rate to AND was also <1%, but 2.5% isolates were intermediate to AND. C. glabrata sensu stricto and C. krusei isolates were also >99% susceptible to MF and AND. However, a 6.3% CAS resistance rate (4/63) was observed in C. krusei in CHIF-NET 2019, and the proportion of C. krusei isolates intermediate to CAS fluctuated between 3.6% and 25.4% over the four surveillance years. Besides, CAS intermediate rates in C. glabrata sensu stricto increased gradually from 1.2% to 5.1% over the 4-year period.
For AMB, over 99% isolates were of WT phenotype in C. albicans (5,365/5,368, 99.9%), C. tropicalis (2,047/2,054, 99.7%), and C. glabrata sensu stricto (1,300/1,306, 99.5%), while 4.0% C. parapsilosis sensu stricto (73/1,821) and 2.8% C. krusei (6/213) isolates were NWT. The MIC50 values of 5-FC for C. albicans, C. tropicalis, C. glabrata sensu stricto, and C. parapsilosis sensu stricto remained consistently low (0.06–0.12 μg/mL) over the surveillance period. In contrast, C. krusei exhibited higher 5-FC MIC50 values, ranging from 8 to 16 μg/mL (Table S1).
Candidemia
Among the 4,686 candidemia isolates, species distribution in surgical wards and outpatient/emergency settings was generally consistent with the overall IC distribution in these departments (Fig. 2b). However, notable discrepancies in species distribution between candidemia and overall IC were observed in the ICU and internal medicine wards. In the ICU wards, although C. albicans remained the most common species causing candidemia, its proportion (672/1,802, 37.3%) was lower than that observed among all IC cases in this setting (1,865/3,932, 47.4%). Meanwhile, C. parapsilosis sensu stricto ranked second (398/1,802, 22.1%), exceeding C. tropicalis (291/1,802, 16.1%), which also differed from the species ranking observed in overall IC cases in the ICU. In medical wards, C. tropicalis has become the leading cause of candidemia (425/1,059, 40.1%), surpassing C. albicans (257/1,059, 24.3%) and C. parapsilosis sensu stricto (188/1,059, 17.8%).
Among different age groups, patients aged 46–65 years accounted for the highest proportion of candidemia isolates (1,787/4,686, 38.1%) (Fig. 2c). The distribution of Candida species and the proportional incidence of candidemia across different age groups remained consistent with previous findings in CHIF-NET 2015–2017 (10). The antifungal susceptibility of the five most common Candida species isolated from blood to FZ, VOR, and CAS is shown in Fig. 2c through f. C. tropicalis exhibited the most notable azole resistance, and its overall susceptibility rate was only 49.6% (493/994) to FZ and 42.9% (426/994) to VOR over the 4-year period. Corresponding resistance rates of C. tropicalis to FZ and VOR were 42.5% (422/994) and 38.9% (387/994), respectively. The susceptibility rates had a further decline, compared to the previous reporting period (63.5% and 49.2%, respectively) (10). For CAS, the highest resistance rate was observed in C. krusei (2/52, 3.8%), followed by C. tropicalis (14/994, 1.4%). Resistance rates to CAS in C. albicans, C. glabrata sensu stricto, and C. parapsilosis sensu stricto remained below 1%. For FZ, VOR, and CAS, susceptibility rates were generally lower in candidemia isolates than in the overall IC population.
Cross-resistance and multi-drug resistance to azoles or echinocandins
We analyzed the prevalence of cross-resistance and multi-drug resistance across the four tested azoles (FZ, VOR, IZ, and PZ), three echinocandins (CAS, MF, and AND), and amphotericin B (AMB). The results are shown in Table 2. Among the azoles, C. glabrata sensu stricto had the highest rate of azole cross-resistance, with 34.9% of strains resistant to at least two azole drugs. Besides, 17.0% of C. tropicalis strains are resistant to all four azole drugs. Although overall resistance rates to echinocandins were low, isolates that are cross-resistant to all three echinocandins and multi-drug resistant have been identified in most of the common Candida species including C. albicans, C. tropicalis, C. parapsilosis sensu stricto, and C. glabrata sensu stricto.
TABLE 2.
Cross- and multi-drug resistance in CHIF-NET 2018–2021
| Species | Cross-resistance to azoles (%)a | Cross-resistance to echinocandins (%) | Multi-drug resistance (%) | |||
|---|---|---|---|---|---|---|
| 2 | 3 | 4 | 2 | 3 | ||
| C. albicans (n = 5,368) | 1.7 | 1.6 | 0.0 | 0.1 | 0.1 | 0.1 |
| C. tropicalis (n = 2,054) | 3.9 | 12.0 | 17.0 | 0.2 | 0.8 | 1.1 |
| C. parapsilosis sensu stricto (n = 1,821) | 2.0 | 0.1 | 0.1 | 0.0 | 0.2 | 1.0 |
| C. glabrata sensu stricto (n = 1,306) | 22.5 | 7.4 | 5.0 | 0.1 | 0.5 | 1.1 |
| C. metapsilosis (n = 235) | 0.9 | 0.0 | 0.4 | 0.0 | 0.4 | 1.7 |
| C. krusei (n = 213)b | 1.4 | 0.0 | 0.0 | 0.0 | 0.0 | 2.3 |
| C. orthopsilosis (n = 165) | 23.0 | 6.1 | 0.6 | 0.0 | 0.0 | 1.2 |
Cross-resistance: R or NWT to ≥2 agents within the same antifungal class (e.g., resistance to 2, 3, or 4 azole drugs).
Because C. krusei is intrinsically resistant to FZ, FZ was not included in cross-resistance and multi-drug resistance analyses for this species.
Trends for antifungal susceptibility of major IC species over 12 years
We conducted a longitudinal comparison of the resistance trends of FZ and VOR (Fig. 3) against key Candida species over the 12 years since the establishment of CHIF-NET, including C. albicans, C. tropicalis, C. parapsilosis sensu stricto, C. glabrata sensu stricto, and C. krusei. In general, FZ susceptibility remained stable in C. albicans and C. parapsilosis sensu stricto (susceptibility rates >90%). C. glabrata sensu stricto exhibited increasing FZ resistance in CHIF-NET 2010–2014 (from 11.9% to 24.4%), followed by a sharp decline (6.2%) in CHIF-NET 2015 and a recent gradual rise to 18.0%. FZ resistance in C. tropicalis increased from <10% during CHIF-NET 2010–2012 to 34.5% in CHIF-NET 2019, accompanied by a decline in susceptibility from 94.3% to 51.7%. Both trends partially reversed in CHIF-NET 2020–2021, with FZ susceptibility rates rebounding to approximately 60%. For VOR, susceptibility rates for C. albicans and C. parapsilosis sensu stricto remained above 95%, with only a few exceptions. The longitude VOR susceptibility trend in C. tropicalis was similar to that of FZ. Susceptibility remained high (>92%) during CHIF-NET 2010–2012 but declined sharply thereafter, reaching a lowest level of 39.8% in CHIF-NET 2018, and began to reverse and rebound to approximately 60% in CHIF-NET 2020–2021. MF susceptibility testing for major Candida species causing invasive candidiasis has been conducted since CHIF-NET 2015. As shown in Fig. S1, resistance rates to MF remained consistently low over the seven-year monitoring period (CHIF-NET 2015–2021).
Fig 3.
Trends in antifungal susceptibility among major Candida species causing invasive candidiasis from CHIF-NET 2010–2021. (a) Fluconazole. (b) Voriconazole. Annual data are presented from left to right, starting in CHIF-NET 2010 and ending in CHIF-NET 2021. Abbreviations: S, susceptible; R, resistant; WT, wild type; NWT, non-wild type.
DISCUSSION
Over the 12-year period since the initiation of the CHIF-NET study, the isolation rates of common Candida species have remained relatively stable, and the top five species have consistently been C. albicans, C. parapsilosis species complex, C. tropicalis, C. glabrata species complex, and C. krusei.
In 2022, the World Health Organization developed the first fungal priority pathogens list (WHO FPPL) (14). Both C. auris and C. albicans were included in the Critical Priority Group. C. auris (now classified as Clavispora auris), in particular, has garnered global attention in recent years due to its potential for rapid transmission and multi-drug resistance. Recent data from the SENTRY Antifungal Surveillance Program highlight a notable increase in the prevalence of C. auris isolates, rising from <0.1% prior to 2018 to 1.6% in 2022 (15). However, in the CHIF-NET surveillance program, only five C. auris were isolated in 2018, all from the same hospital, which suggests a potential localized outbreak. Nevertheless, the emergence and nosocomial transmission of C. auris in China have been documented in other more recent studies. A national retrospective survey conducted from January 2016 to August 2023 identified a total of 312 cases from 18 hospitals across 10 provinces, with a marked rise observed after 2021 (16). Notably, Guangdong Province in South China experienced an explosive outbreak, underscoring the ongoing challenges posed by this pathogen (16).
C. albicans remains the predominant causative agent of IC globally, while a number of studies have reported an increasing trend in non-albicans Candida species (17, 18). Notably, the proportion of C. albicans among candidemia cases in our study was only 33.8% (1,582/4,686), which is lower than that reported in the UK (accounting for 44.8% in 2020) (19) and the US (where the proportion declined from 52% in 1992–1993 to 41% in 2008–2011) (20). This underscores the substantial clinical challenge posed by non-albicans Candida species in China.
The other four most prevalent Candida species, i.e., C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei, were listed in the High Priority Group of the WHO FPPL. C. parapsilosis, as the most prevalent non-albicans Candida species, exhibits a high isolation rate. C. parapsilosis infections have become particularly concerning in the past few years due to a strong rise in azole resistance and a number of fluconazole-resistant C. parapsilosis nosocomial outbreaks (21–23). Of note, species within the C. parapsilosis complex differed in isolation frequency and exhibited distinct antifungal resistance profiles, underscoring the importance of accurate species-level identification for guiding antifungal therapy (24). Notably, C. orthopsilosis displayed markedly higher FZ resistance in our study and reached 62.1% in CHIF-NET 2020. In contrast, C. metapsilosis and C. parapsilosis sensu stricto were less resistant (FZ resistance rate around 5%). However, in CHIF-NET 2021, a notable increase in fluconazole resistance was observed in both C. metapsilosis and C. parapsilosis sensu stricto. Additionally, C. parapsilosis can persist in hospital environments, and the recently recognized phenomenon of antifungal heteroresistance poses a new clinical challenge (25).
C. tropicalis, known for its high prevalence in tropical geographic regions (26), is the most common non-albicans Candida species causing candidemia in India, Thailand, and Singapore (27). The 30-day mortality of candidemia caused by C. tropicalis has been reported to be up to 52% (28). In this study, the prevalence of C. tropicalis was notably higher in medical wards among candidemia cases. Besides, C. tropicalis exhibits the highest rates of azole resistance among all common Candida species in China. Notably, fluconazole resistance rates varied across the world, typically ranging from 0% to 18% (29). Fluconazole remained one of the cost-effective first-line antifungal agents for prophylaxis against IC in hematopoietic stem cell transplant recipients (30, 31). Primary fluconazole resistance is relatively uncommon in C. tropicalis; however, resistance may develop upon drug exposure (32), and extensive azole use in clinical practice may contribute to the increasing resistance observed in this species (33). However, a recent study demonstrated that agricultural triazole fungicides can also induce cross-resistance to clinical azole drugs in C. tropicalis because these compounds share the same molecular target (34). Similar concerns regarding agriculture-driven azole resistance have previously been recognized in Aspergillus fumigatus (35). Therefore, coordinated efforts across human, animal, and environmental sectors are needed to reduce the risk of cross-sector antimicrobial resistance.
In our study, C. glabrata sensu stricto (now classified as Nakaseomyces glabrata) accounted for 11.2% of IC and 12.7% of candidemia cases, ranking fourth in both groups. In Japan, C. glabrata has been reported as the predominant non-albicans Candida species, comprising 19.5% of candidemia isolates (36). In comparison, surveillance data from the UK indicate that C. glabrata remained the most frequently isolated non-albicans Candida species, accounting for 29.4% and 25.5% of candidemia episodes in 2019 and 2020, respectively (19). The SENTRY Program (1997–2016) reported a C. glabrata isolation rate of 24.3% among candidemia in North America (37). These results indicated regional variations in the epidemiology of this species. Moreover, antifungal susceptibility in C. glabrata also varies considerably across regions (38). In the US, micafungin resistance in C. glabrata increased from negligible levels during 2001–2007 to over 6% in sensu stricto 2014–2016 (37), while in Japan, resistance rates ranged from 8.0% to 17.8% in a study spanning 2010–2019 (36). Notably, about 10% of clinical C. glabrata isolates have been reported to exhibit multi-drug resistance to both azole and echinocandin agents (39, 40). In contrast, the echinocandin resistance in China remained low and <1% in C. glabrata till CHIF-NET 2021. Alarmingly, among echinocandin-resistant C. glabrata isolates, around 36%–38% also exhibited fluconazole resistance (39). However, in our study, the overall multi-drug resistance rate in C. glabrata was 1.1%, and only 0.6% of isolates exhibited resistance to both azoles and echinocandins. However, it should be noted that echinocandin use has increased substantially in China in recent years, underscoring the need for continued surveillance to monitor emerging resistance trends among C. glabrata and other Candida species.
Indeed, over the 12 years of CHIF-NET surveillance (2010–2021), notable changes in antifungal resistance were observed. The most notable change was the marked decline in susceptibility of C. tropicalis to both FZ and VOR, with susceptibility rates decreasing from over 90% in the early surveillance period to approximately 50%. The observed increase in resistance among C. tropicalis isolates in China is largely attributed to the clonal dissemination of strains exhibiting novel antifungal resistance mechanisms within the healthcare settings (41, 42). While fluconazole resistance remained relatively low in C. albicans and C. parapsilosis, consistent shifts in susceptibility were observed, highlighting the importance of ongoing antifungal resistance surveillance.
The limitations of our study remained. As a laboratory-based study, our data lack detailed clinical information. Additionally, our data are compiled biannually, and the interval from isolate transportation to completion of analysis takes approximately 8–10 months. Consequently, surveillance results may lag behind the most recent epidemiological developments, such as the rapid spread of C. auris in recent years. Efforts are ongoing to further improve the timeliness and completeness of the surveillance system.
Conclusion
IC poses a significant global health threat, as the rising antifungal resistance increasingly complicates treatment and infection control worldwide. This study provides updated data on the epidemiology and antifungal susceptibility of IC pathogens in China. We observed high resistance rates, particularly among non-albicans Candida species such as C. tropicalis, along with the emergence of multi-drug resistance. These findings support more informed empirical therapy and antifungal stewardship efforts and highlight the need for continued surveillance and targeted clinical management to reduce the burden of IC in China and beyond.
ACKNOWLEDGMENTS
We acknowledge all members of the CHIF-NET study group. This study was supported by the Expert Committee on Clinical Use of Antimicrobials and Evaluation of Antimicrobial Resistance in China. We appreciate the support of all the members of this committee. We are grateful to the Center for Bioinformatics, and the Clinical Biobank, National Infrastructures for Translational Medicine, Institute of Clinical Medicine and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, , for providing computational resources and biospecimen processing.
This work was supported by the National Natural Science Foundation of China (grant no. 82572631), the National High Level Hospital Clinical Research Funding (grant no. 2025-PUMCH-A-088), the Peking Union Medical College Hospital Talent Cultivation Program (Category C, no. UBJ11583; Category D, no. UHB12289), the Young Elite Scientists Sponsorship Program of the Beijing High Innovation Plan (no. 20250905), and the CAMS Innovation Fund for Medical Sciences (CIFMS) (grant no. 2025-I2M-XHXX-015).
Contributor Information
Ying-Chun Xu, Email: xycpumch@139.com.
Meng Xiao, Email: cjtcxiaomeng@aliyun.com.
Andreas H. Groll, University Children's Hospital Münster, Münster, Germany
DATA AVAILABILITY
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
ETHICS APPROVAL
This study was reviewed and approved by the Institutional Review Board (IRB) of Peking Union Medical College Hospital (nos. S-263, I-22PJ385, and I-24PJ2112).
SUPPLEMENTAL MATERIAL
The following material is available online at https://doi.org/10.1128/aac.00035-26.
Fig. S1; Table S1.
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REFERENCES
- 1. Kullberg BJ, Arendrup MC. 2015. Invasive candidiasis. N Engl J Med 373:1445–1456. doi: 10.1056/NEJMra1315399 [DOI] [PubMed] [Google Scholar]
- 2. Parsons MG, Diekema DJ. 2023. What is new in fungal infections? Mod Pathol 36:100187. doi: 10.1016/j.modpat.2023.100187 [DOI] [PubMed] [Google Scholar]
- 3. Paiva J-A, Pereira JM. 2023. Treatment of invasive candidiasis in the era of Candida resistance. Curr Opin Crit Care 29:457–462. doi: 10.1097/MCC.0000000000001077 [DOI] [PubMed] [Google Scholar]
- 4. Ramos LS, Barbosa PF, Lorentino CMA, Lima JC, Braga AL, Lima RV, Giovanini L, Casemiro AL, Siqueira NLM, Costa SC, Rodrigues CF, Roudbary M, Branquinha MH, Santos ALS. 2025. The multidrug-resistant Candida auris, Candida haemulonii complex and phylogenetic related species: Insights into antifungal resistance mechanisms. Curr Res Microb Sci 8:100354. doi: 10.1016/j.crmicr.2025.100354 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Rhodes J. 2019. Rapid worldwide emergence of pathogenic fungi. Cell Host Microbe 26:12–14. doi: 10.1016/j.chom.2019.06.009 [DOI] [PubMed] [Google Scholar]
- 6. Rodríguez Stewart RM, Gold JAW, Chiller T, Sexton DJ, Lockhart SR. 2023. Will invasive fungal infections be the last of us? The importance of surveillance, public-health interventions, and antifungal stewardship. Expert Rev Anti Infect Ther 21:787–790. doi: 10.1080/14787210.2023.2227790 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Lass-Flörl C, Kanj SS, Govender NP, Thompson GR 3rd, Ostrosky-Zeichner L, Govrins MA. 2024. Invasive candidiasis. Nat Rev Dis Primers 10:20. doi: 10.1038/s41572-024-00503-3 [DOI] [PubMed] [Google Scholar]
- 8. Wang H, Xiao M, Chen S-A, Kong F, Sun Z-Y, Liao K, Lu J, Shao H-F, Yan Y, Fan H, Hu Z-D, Chu Y-Z, Hu T-S, Ni Y-X, Zou G-L, Xu Y-C. 2012. In vitro susceptibilities of yeast species to fluconazole and voriconazole as determined by the 2010 national China hospital invasive fungal surveillance NET (CHIF-NET) study. J Clin Microbiol 50:3952–3959. doi: 10.1128/JCM.01130-12 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Xiao M, Sun Z-Y, Kang M, Guo D-W, Liao K, Chen S-A, Kong F, Fan X, Cheng J-W, Hou X, Zhou M-L, Li Y, Yu S-Y, Huang J-J, Wang H, Xu Y-C. 2018. Five-year national surveillance of invasive candidiasis: species distribution and azole susceptibility from the China hospital invasive fungal surveillance NET (CHIF-NET) study. J Clin Microbiol 56:e00577-18. doi: 10.1128/JCM.00577-18 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Xiao M, Chen S-A, Kong F, Xu X-L, Yan L, Kong H-S, Fan X, Hou X, Cheng J-W, Zhou M-L, Li Y, Yu S-Y, Huang J-J, Zhang G, Yang Y, Zhang J-J, Duan S-M, Kang W, Wang H, Xu Y-C. 2020. Distribution and antifungal susceptibility of Candida species causing candidemia in China: an update from the CHIF-NET study. J Infect Dis 221:S139–S147. doi: 10.1093/infdis/jiz573 [DOI] [PubMed] [Google Scholar]
- 11. Yi Q, Xiao M, Fan X, Zhang G, Yang Y, Zhang J-J, Duan S-M, Cheng J-W, Li Y, Zhou M-L, Yu S-Y, Huang J-J, Chen X-F, Hou X, Kong F, Kudinha T, Xu Y-C. 2021. Evaluation of Autof MS 1000 and Vitek MS MALDI-TOF MS system in identification of closely-related yeasts causing invasive fungal diseases. Front Cell Infect Microbiol 11:628828. doi: 10.3389/fcimb.2021.628828 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. CLSI . 2022. CLSI supplement M27M44S. In Performance standards for antifungal susceptibility testing of yeasts, 3rd ed. Clinical and Laboratory Standards Institute. [Google Scholar]
- 13. CLSI . 2022. CLSI supplement M57S. In Epidemiological cutoff values for antifungal susceptibility testing, 4th ed. Clinical and Laboratory Standards Institute. [Google Scholar]
- 14. World Health Organization . 2022. WHO fungal priority pathogens list to guide research, development and public health action. Geneva [Google Scholar]
- 15. Castanheira M, Deshpande LM, Rhomberg PR, Carvalhaes CG. 2024. Recent increase in Candida auris frequency in the SENTRY surveillance program: antifungal activity and genotypic characterization. Antimicrob Agents Chemother 68:e0057024. doi: 10.1128/aac.00570-24 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Bing J, Du H, Guo P, Hu T, Xiao M, Lu S, Nobile CJ, Chu H, Huang G. 2024. Candida auris-associated hospitalizations and outbreaks, China, 2018–2023. Emerg Microbes Infect 13:2302843. doi: 10.1080/22221751.2024.2302843 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Guinea J. 2014. Global trends in the distribution of Candida species causing candidemia. Clin Microbiol Infect 20:5–10. doi: 10.1111/1469-0691.12539 [DOI] [PubMed] [Google Scholar]
- 18. Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. 2018. Invasive candidiasis. Nat Rev Dis Primers 4:18026. doi: 10.1038/nrdp.2018.26 [DOI] [PubMed] [Google Scholar]
- 19. UK Health Security Agency . 2025. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) report 2020 to 2021. Available from: https://www.gov.uk/government/publications/english-surveillance-programme-antimicrobial-utilisation-and-resistance-espaur-report
- 20. Seagle EE, Williams SL, Chiller TM. 2021. Recent trends in the epidemiology of fungal infections. Infect Dis Clin North Am 35:237–260. doi: 10.1016/j.idc.2021.03.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Daneshnia F, de Almeida Júnior JN, Ilkit M, Lombardi L, Perry AM, Gao M, Nobile CJ, Egger M, Perlin DS, Zhai B, Hohl TM, Gabaldón T, Colombo AL, Hoenigl M, Arastehfar A. 2023. Worldwide emergence of fluconazole-resistant Candida parapsilosis: current framework and future research roadmap. Lancet Microbe 4:e470–e480. doi: 10.1016/S2666-5247(23)00067-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Siopi M, Georgiou P-C, Paranos P, Beredaki M-I, Tarpatzi A, Kalogeropoulou E, Damianidou S, Vasilakopoulou A, Karakosta P, Pournaras S, Meletiadis J. 2024. Increase in candidemia cases and emergence of fluconazole-resistant Candida parapsilosis and C. auris isolates in a tertiary care academic hospital during the COVID-19 pandemic, Greece, 2020 to 2023. Euro Surveill 29:2300661. doi: 10.2807/1560-7917.ES.2024.29.29.2300661 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Díaz-García J, Gómez A, Alcalá L, Reigadas E, Sánchez-Carrillo C, Pérez-Ayala A, Gómez-García de la Pedrosa E, González-Romo F, Merino-Amador P, Cuétara MS, García-Esteban C, Quiles-Melero I, Zurita ND, Muñoz-Algarra M, Sánchez-Romero I, Durán-Valle MT, Sánchez-García A, Alcoceba E, Muñoz P, Escribano P, Guinea J. 2022. Evidence of fluconazole-resistant Candida parapsilosis genotypes spreading across hospitals located in Madrid, Spain and Harboring the Y132F ERG11p substitution. Antimicrob Agents Chemother 66:e0071022. doi: 10.1128/aac.00710-22 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Govrins M, Lass-Flörl C. 2024. Candida parapsilosis complex in the clinical setting. Nat Rev Microbiol 22:46–59. doi: 10.1038/s41579-023-00961-8 [DOI] [PubMed] [Google Scholar]
- 25. Zhai B, Liao C, Jaggavarapu S, Tang Y, Rolling T, Ning Y, Sun T, Bergin SA, Gjonbalaj M, Miranda E, Babady NE, Bader O, Taur Y, Butler G, Zhang L, Xavier JB, Weiss DS, Hohl TM. 2024. Antifungal heteroresistance causes prophylaxis failure and facilitates breakthrough Candida parapsilosis infections. Nat Med 30:3163–3172. doi: 10.1038/s41591-024-03183-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Bohner F, Gacser A, Toth R. 2021. Epidemiological attributes of Candida species in tropical regions. Curr Trop Med Rep 8:59–68. doi: 10.1007/s40475-021-00226-5 [DOI] [Google Scholar]
- 27. Tan BH, Chakrabarti A, Li RY, Patel AK, Watcharananan SP, Liu Z, Chindamporn A, Tan AL, Sun PL, Wu UI, et al. 2015. Incidence and species distribution of candidaemia in Asia: a laboratory-based surveillance study. Clin Microbiol Infect 21:946–953. doi: 10.1016/j.cmi.2015.06.010 [DOI] [PubMed] [Google Scholar]
- 28. Liu W-L, Huang Y-T, Hsieh M-H, Hii I-M, Lee Y-L, Ho M-W, Liu C-E, Chen Y-H, Wang F-D. 2019. Clinical characteristics of Candida tropicalis fungaemia with reduced triazole susceptibility in Taiwan: a multicentre study. Int J Antimicrob Agents 53:185–189. doi: 10.1016/j.ijantimicag.2018.10.015 [DOI] [PubMed] [Google Scholar]
- 29. Keighley C, Kim HY, Kidd S, Chen S-A, Alastruey A, Dao A, Bongomin F, Chiller T, Wahyuningsih R, Forastiero A, Al-Nuseirat A, Beyer P, Gigante V, Beardsley J, Sati H, Morrissey CO, Alffenaar J-W. 2024. Candida tropicalis-a systematic review to inform the World health organization of a fungal priority pathogens list. Med Mycol 62:myae040. doi: 10.1093/mmy/myae040 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Maertens JA, Girmenia C, Brüggemann RJ, Duarte RF, Kibbler CC, Ljungman P, Racil Z, Ribaud P, Slavin MA, Cornely OA, Peter Donnelly J, Cordonnier C, European Conference on Infections in Leukaemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS) and, European Conference on Infections in Leukaemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS) and the European LeukemiaNet (ELN) . 2018. European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia. J Antimicrob Chemother 73:3221–3230. doi: 10.1093/jac/dky286 [DOI] [PubMed] [Google Scholar]
- 31. Medical Mycology Society of Chinese Medicine and Education Association; Chinese Society of Hematology CMA . 2023. Chinese expert consensus for invasive fungal disease in patients after hematopoietic stem cell transplantation(2023). Chin J Hematol 44:92–97. doi: 10.3760/cma.j.issn.0253-2727.2023.02.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Ann Chai LY, Denning DW, Warn P. 2010. Candida tropicalis in human disease. Crit Rev Microbiol 36:282–298. doi: 10.3109/1040841X.2010.489506 [DOI] [PubMed] [Google Scholar]
- 33. Khalifa HO, Watanabe A, Kamei K. 2022. Azole and echinocandin resistance mechanisms and genotyping of Candida tropicalis in Japan: cross-boundary dissemination and animal–human transmission of C. tropicalis infection. Clin Microbiol Infect 28:302. doi: 10.1016/j.cmi.2021.10.004 [DOI] [PubMed] [Google Scholar]
- 34. Hu T, Zheng Q, Cao C, Li S, Huang Y, Guan Z, Ji L, Bing J, Du H, Perry AM, Nobile CJ, Li B, Chu H, Huang G. 2025. An agricultural triazole induces genomic instability and haploid cell formation in the human fungal pathogen Candida tropicalis. PLoS Biol 23:e3003062. doi: 10.1371/journal.pbio.3003062 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Snelders E, van der Lee HAL, Kuijpers J, Rijs AJMM, Varga J, Samson RA, Mellado E, Donders ART, Melchers WJG, Verweij PE. 2008. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med 5:e219. doi: 10.1371/journal.pmed.0050219 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Kajihara T, Yahara K, Nagi M, Kitamura N, Hirabayashi A, Hosaka Y, Abe M, Miyazaki Y, Sugai M. 2022. Distribution, trends, and antifungal susceptibility of Candida species causing candidemia in Japan, 2010–2019: a retrospective observational study based on national surveillance data. Med Mycol 60:myac071. doi: 10.1093/mmy/myac071 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Pfaller MA, Diekema DJ, Turnidge JD, Castanheira M, Jones RN. 2019. Twenty years of the SENTRY antifungal surveillance program: results for Candida species from 1997–2016. Open Forum Infect Dis 6:S79–S94. doi: 10.1093/ofid/ofy358 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Shantal C-J, Juan C-C, Lizbeth B-U, Carlos H-G, Estela G-PB. 2022. Candida glabrata is a successful pathogen: an artist manipulating the immune response. Microbiol Res 260:127038. doi: 10.1016/j.micres.2022.127038 [DOI] [PubMed] [Google Scholar]
- 39. Askari F, Kaur R. 2025. Candida glabrata: a tale of stealth and endurance. ACS Infect Dis 11:4–20. doi: 10.1021/acsinfecdis.4c00477 [DOI] [PubMed] [Google Scholar]
- 40. Khalifa HO, Arai T, Majima H, Watanabe A, Kamei K. 2020. Genetic basis of azole and echinocandin resistance in clinical Candida glabrata in Japan. Antimicrob Agents Chemother 64:e00783-20. doi: 10.1128/AAC.00783-20 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. Hu T, Wang S, Bing J, Zheng Q, Du H, Li C, Guan Z, Bai F-Y, Nobile CJ, Chu H, Huang G. 2023. Hotspot mutations and genomic expansion of ERG11 are major mechanisms of azole resistance in environmental and human commensal isolates of Candida tropicalis. Int J Antimicrob Agents 62:107010. doi: 10.1016/j.ijantimicag.2023.107010 [DOI] [PubMed] [Google Scholar]
- 42. Fan X, Dai R-C, Zhang S, Geng Y-Y, Kang M, Guo D-W, Mei Y-N, Pan Y-H, Sun Z-Y, Xu Y-C, Gong J, Xiao M. 2023. Tandem gene duplications contributed to high-level azole resistance in a rapidly expanding Candida tropicalis population. Nat Commun 14:8369. doi: 10.1038/s41467-023-43380-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Fig. S1; Table S1.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.