Analysis of Candida auris resistance and associated risk factors in hospitalized patients at a tertiary care hospital in China

Abstract

Candida auris (Candidozyma auris, C. auris) is a significant concern in infection prevention. This study aims to analyze the antifungal susceptibility of C. auris isolates and risk factors of C. auris-associated infections in hospitalized patients at a tertiary care hospital in China, providing evidence to guide infection control strategies and effectively prevent in-hospital transmission. A retrospective analysis was conducted to evaluate the quarterly trends in newly identified Candida isolates from January 1, 2022, to March 31, 2025. Antifungal susceptibility profiles of C. auris were assessed and compared with those of other Candida species. In addition, the clinical characteristics of hospitalized patients infected with C. auris were analyzed and compared to those of patients infected with other Candida species. The number of newly identified C. auris infections demonstrated an upward trend over the study period. In our hospital, C. auris showed a fluconazole resistance rate of 77.42% and an amphotericin B resistance rate of 3.23%. Patients with C. auris infection had a significantly longer median hospital stay [17 (14–25) days] compared to those infected with other Candida species [12 (7–19) days] (p < 0.001), as well as a significantly higher mortality rate (p < 0.001). A multivariable regression analysis of Candida infections showed that intensive care unit admission (OR 1.502, 95% CI 1.273–1.923), hypertension (OR 1.476, 95% CI 1.207–1.807), immunosuppressive status (OR 1.179, 95% CI 1.036–1.483), and the presence of indwelling medical devices (OR 1.265, 95% CI 1.065–1.422) were all independently associated with infection risk, with statistical significance (p < 0.05). Ongoing vigilance is warranted for fluconazole-resistant C. auris, and stringent implementation of infection prevention and control measures remains essential to limit its spread and impact in healthcare settings.

Introduction

Fungal infections have a substantial global health burden, causing over 1.5 million deaths annually. Notably, the incidence of invasive candidiasis has been rising significantly, with an estimated 700,000 new cases occurring each year¹. Invasive candidiasis frequently affects critically ill patients and is associated with a range of risk factors, including an aging population with multiple comorbidities, prolonged hospitalization, diabetes, the use of invasive medical devices, frequent exposure to broad-spectrum antibiotics, major surgical interventions, stem cell transplantation, and immunosuppressive therapy². Candida auris (Candidozyma auris, C. auris) can be transmitted through contact³, leading to outbreaks of healthcare-associated infections, Examples include the C. auris hospital outbreak in Colombia from 2015 to 2016⁴, multiple outbreaks reported in healthcare facilities in Israel between 2014 and 2022⁵, and the hospital transmission of C. auris in China in 2023⁶. In 2018, the first case of C. auris in mainland China was identified, isolated from the bronchoalveolar lavage fluid of a hospitalized female patient in Beijing⁷. Between 2018 and 2023, 312 clinical cases of C. auris were reported across 10 provincial regions in China⁸. By the end of December 2024, this number had risen to 1166 cases nationwide⁹, reflecting rapid domestic spread and a marked increase in both infection. Therefore, infection preventionists must maintain vigilant surveillance of this contact-transmissible healthcare-associated pathogen. This analysis of antifungal susceptibility and associated risk factors provides critical insights to guide infection control strategies aimed at effectively preventing and interrupting the transmission of C. auris within hospital settings.

Materials and methods

Setting

This study was carried out at Guangdong Second Provincial General Hospital, a university-affiliated tertiary hospital located in Guangzhou, Guangdong Province, China, with a bed capacity of approximately 1730. This retrospective study analyzed the quarterly incidence of newly diagnosed Candida infections from January 1, 2022, to March 31, 2025. Clinical characteristics of C. auris infections were compared with those of other Candida species identified in hospitalized patients during the same period. In addition, antimicrobial susceptibility profiles of C. auris isolates were comprehensively evaluated.

Ethics approval and consent statement

All methods in this study were carried out in accordance with relevant guidelines and regulations. The study was approved by the Ethics Committee of The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China (Approval No. 2025-KY-KZ-108-01). Due to the retrospective nature of the study, the Ethics Committee of The Affiliated Guangdong Second Provincial General Hospital of Jinan University waived the need of obtaining informed consent and the use of a de-identified database.

Study population and inclusion criteria

Both community-acquired and hospital-acquired infections were included in this study. Infections were diagnosed based on a comprehensive evaluation of the patient’s clinical manifestations, laboratory results, imaging findings, medical history, and the use of antifungal agents, in accordance with established diagnostic criteria. Colonization was defined as the presence of C. auris in clinical specimens without compatible clinical evidence of infection. Only cases meeting the criteria for clinically significant infections were included, while isolates considered to represent colonization without corresponding clinical evidence were excluded. Exclusion criteria included contaminated specimens, cases with incomplete data, and patients under 18 years of age. A total of 31 C. auris isolates from patients aged ≥ 18 years with complete clinical data and confirmed clinical infection were included in the study, while 54 colonization isolates were excluded.

Data collection

Clinical characteristics and antimicrobial susceptibility data of C. auris and other Candida species isolated from hospitalized patients were extracted from the hospital information system KR-Lis V5.0 (Guangdong Kangruan Technology Co., Ltd.). Duplicate isolates from the same anatomical site and the same patient were excluded, and only the first isolate was retained for analysis. Clinical baseline data—including age, sex, length of hospital stay, and underlying risk factors—were obtained from the electronic medical record system V6.0 (Beijing Jiahe Meikang Information Technology Co., Ltd.) and the hospital’s intelligent infection management system (Shanghai Lilian Information Technology Co., Ltd.). Risk factors included pre-existing conditions (hypertension, diabetes, chronic obstructive pulmonary disease, renal insufficiency, heart failure, hepatic insufficiency, and immunodeficiency, based on pre-admission records) and the presence of invasive indwelling devices (central venous catheters, urinary catheters, and endotracheal tubes) during hospitalization. Patients were categorized according to clinical outcomes as discharged or deceased. The types of infections cases included bloodstream infections, urinary tract infections, pulmonary infections, and infections at other sites.

Invasive indwelling device–related infections were defined according to established clinical criteria. Catheter-associated urinary tract infection was considered when a urinary tract infection occurred during indwelling urinary catheterization or within 48 h after catheter removal, accompanied by relevant clinical symptoms and positive urine culture in the absence of another source of infection. Ventilator-associated pneumonia was defined as pneumonia developing at least 48 h after endotracheal intubation or tracheostomy with mechanical ventilation, characterized by new or progressive pulmonary infiltrates on chest imaging together with clinical features such as fever, purulent tracheal secretions, or abnormal leukocyte counts. Catheter-related bloodstream or local infections were defined as primary infections occurring during vascular catheterization or within 48 h after catheter removal, not attributable to another focus of infection, and confirmed by positive blood cultures or clinical evidence of local inflammation (e.g., erythema, tenderness, or purulence at the insertion site). Only cases that met the diagnostic criteria for ventilator-associated pneumonia or catheter-associated urinary tract infection were classified as infections, whereas respiratory or urine isolates considered colonization were excluded from the analysis.

Pathogen identification and antimicrobial susceptibility testing

Bacterial identification was performed using the VITEK-MS automated matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system. Antifungal susceptibility testing was conducted using the ATB FUNGUS 3 kit (bioMérieux, France), and results were interpreted according to the clinical breakpoints and epidemiological cutoff values defined by Clinical and Laboratory Standards Institute (CLSI) M60 and CLSI M59 guidelines. Quality control strains included Candida parapsilosis ATCC 22,019 and Candida krusei ATCC 6258.

Infection prevention and control of C. auris in our hospital

Multidisciplinary collaboration

Our hospital had established a multidisciplinary team that included the medical, nursing, clinical laboratory, infection control, and clinical pharmacy departments. C. auris cases were assessed based on clinical manifestations and epidemiological history in order to achieve prompt identification, and effective contact isolation measures were implemented to prevent transmission.

Policies, workflows, and emergency plans

A comprehensive C. auris prevention policy and early-warning system had been developed. Dedicated infection control personnel monitor cases daily, and an emergency response plan was in place with biannual drills to ensure effective interdepartmental coordination.

Support measures for infection control

Adequate personal protective equipment and disinfectants were provided, and medical staff received regular training on C. auris prevention and control. For each identified case, on-site supervision ensured adherence to infection control measures, with prompt feedback provided.

Active screening

High-risk patients were actively screened upon admission and weekly thereafter until discharge. Screening included axilla, groin, nasal cavity, throat, rectum, and feces, with additional specimens such as urine, wound exudate, or respiratory samples collected as indicated. Environmental and patient-contact surfaces were also sampled. Close contacts of confirmed cases underwent simultaneous screening.

Patient admission and isolation

Infected patients were placed in single rooms. When single rooms were limited, priority was given to patients with higher transmission risk (e.g., acute diarrhea, wound drainage, or indwelling catheters). Isolation orders and appropriate signage were implemented, and dedicated staff strictly adhered to contact precautions. Contact isolation was lifted after two consecutive negative screenings, conducted one week apart, following discontinuation of antifungal therapy.

Statistical analyses

All statistical analyses were performed using SPSS statistical software, version 29.0. Categorical variables were compared using the chi-square test. Counted data were described by the number of cases (percentage), and the Kolmogorov-Smirnov test was used to verify the normality of the data. For continuous variables that followed a normal distribution, the mean ± standard deviation (SD) was used to describe them, and the differences between the groups were assessed using Student’s t test. Continuous non-normally distributed variables were described using the median and interquartile range (IQR, P25, P75), and non-parametric comparisons were performed using the Mann–Whitney U test. A multivariable regression analysis of Candida was conducted using a logistic regression model. All statistical analyses were evaluated at the statistical significance level of p < 0.05 (two-sided).

Results

Epidemiology of Candida species

Candida albicans exhibited the highest number and incidence rate of newly identified infections. From 2022 to the first quarter of 2024, the number of new C. albicans infections showed a steady increase, peaking in the first quarter of 2024 with 168 cases and an incidence rate of 13.08 per 10,000 patient-days, followed by a gradual decline. Candida glabrata displayed a similar pattern, with 63 new infections and an incidence rate of 4.91 per 10,000 patient-days during the same period. The number of Candida tropicalis isolates increased over time, peaking in the third quarter of 2023 with 47 new infections, and the highest incidence rate was observed in the fourth quarter of 2022 at 3.85 per 10,000 patient-days, before gradually declining and stabilizing in 2024. Candida parapsilosis reached its peak in the second quarter of 2024, with 16 new cases and an incidence rate of 1.07 per 10,000 patient-days. Since its initial detection in the second quarter of 2023, C. auris has shown a continuous upward trend, with a total of 31 isolates identified by the first quarter of 2025. The incidence of infections caused by other Candida species declined from 1.86 per 10,000 patient-days in the first quarter of 2023 (Fig. 1).

Fig. 1.

Situation of new cases of candidiasis infections and new cases of candidiasis infections per 10,000 patient-days hospitalized from the first quarter of 2022 to the first quarter of 2025.

Antifungal susceptibility of C. auris.

The antifungal susceptibility test results for C. auris are shown in Fig. 2. Among the 31 C. auris isolates, the resistance rate to fluconazole was 77.42%, while resistance to amphotericin B was 3.23%. Regarding voriconazole, 28 isolates had a minimum inhibitory concentration (MIC) ≤ 1 µg/mL, with 2 isolates at 2 µg/mL and 1 isolate at 8 µg/mL. For itraconazole, the MIC distribution was as follows: 19 isolates at 0.125 µg/mL, 5 at 0.25 µg/mL, 6 at 0.5 µg/mL, and 1 at 1 µg/mL. The ATB Fungus 3 system used in our hospital can only detect MIC values for 5-flucytosine ≥ 4 µg/mL and cannot measure lower concentrations. Therefore, all C. auris isolates exhibited an MIC of 4 µg/mL, which is the lowest detectable value for this assay. Caspofungin MICs were 0.25 µg/mL in 20 isolates and 0.125 µg/mL in 11 isolates.

Fig. 2.

Distribution of MIC values for C. auris when treated with various antifungals.

Risk factor analysis of Candida auris

In the comparison of clinical characteristics between C. auris and other Candida species (Table 1), patients with C. auris infection had a longer hospital stay [17^14–25 days] than those with other Candida infections [12^7–19 days] (p < 0.001). Among patients screened upon admission, a higher proportion of those with C. auris had hypertension (p = 0.019). The mortality rate in patients with C. auris infection was significantly higher than that of patients with other Candida species (p < 0.001).

Table 1.

The clinical characteristics of C. auris compared to other Candida species have been analyzed.

Characteristics	Candida auris (n = 31)	Other Candida species (n = 1439)	p value
Age [mean ± SD]	69.35 ± 13.24	65.12 ± 19.29	0.224
Sex, Male—n (%)	22 (70.97)	790 (54.90)	0.075
Intensive care unit—n (%)	17 (54.84)	658 (45.73)	0.314
Length of stay, days—median (interquartile range)	17 (14–25)	12 (7–19)	< 0.001
Pre-existing comorbidities—no. (%)
Diabetes mellitus	8 (25.81)	335 (23.28)	0.742
Hypertension	17 (54.84)	497 (34.54)	0.019
COPD	3 (9.68)	160 (11.12)	0.064
Renal disease	5 (16.13)	240 (16.68)	0.935
Congestive heart failure	7 (22.58)	214 (14.87)	0.235
Chronic liver disease	5 (16.13)	163 (11.33)	0.406
Immunosuppressive status	10 (32.26)	486 (33.77)	0.860
Indwelling medical devices	20 (64.51)	866 (60.18)	0.626
Sites of infection			0.064
Pulmonary infections	15 (48.39)	734 (51.01)
Bloodstream infections	3 (9.68)	32 (2.22)
Urinary tract infections	7 (22.58)	369 (25.64)
Other sites infections	6 (19.35)	304 (21.13)
Outcome—n (%)			< 0.001
Death	6 (19.35)	59 (4.10)
Discharge	25 (80.65)	1380 (95.90)

Multivariable regression analysis of Candida

A multivariable regression analysis of Candida infections showed that intensive care unit admission (OR 1.502, 95% CI 1.273–1.923), hypertension (OR 1.476, 95% CI 1.207–1.807), immunosuppressive status (OR 1.179, 95% CI 1.036–1.483), and the presence of indwelling medical devices (OR 1.265, 95% CI 1.065–1.422) were all independently associated with infection risk, with statistical significance (p < 0.05), as illustrated in Fig. 3.

Fig. 3.

Multivariable regression analysis of Candida. The reference category for intensive care unit admission, hypertension, immunosuppressive status, and indwelling medical devices was “none.” Other variables without statistical significance were not included in the model.

Discussion

Currently, C. auris poses a significant challenge to healthcare facilities and public health due to its ability to cause hospital outbreaks, develop resistance to disinfectants, and persist on human skin and in the healthcare environment, thereby posing a substantial threat to patient health¹⁰. C. auris can colonize the skin, respiratory tract, and urinary tract, and in immunocompromised individuals, it can cause infections in the bloodstream, respiratory tract, urinary tract, superficial wounds, and ear canal. C. auris can survive on the skin and persist in the environment, contaminating surfaces and medical equipment, leading to healthcare-associated infections through direct or indirect contact within hospital settings^11–15. Following the principle of “early detection, early reporting, early isolation, early intervention,” C. auris cases were promptly identified based on clinical manifestations and epidemiological history, and effective contact isolation measures were implemented to prevent transmission. According to the provisional MIC breakpoints for C. auris antifungal susceptibility established by the United States of America Centers for Disease Control and Prevention¹⁶, resistance is defined as follows: fluconazole resistance at an MIC ≥ 32 µg/mL, amphotericin B resistance at an MIC ≥ 2 µg/mL, caspofungin resistance at an MIC ≥ 2 µg/mL. Nevertheless, according to the recently updated European Committee for Antimicrobial Susceptibility Testing (EUCAST) breakpoints (R > 2 mg/L), all isolates are considered susceptible to amphotericin B, provided that an elevated dose is administered¹⁷.

The CLSI has defined breakpoints for rezafungin against C. auris, while breakpoints for other antifungals remain undefined. Reported MICs of amphotericin B for C. auris vary substantially across antifungal susceptibility testing (AFST) methods. Although CLSI and EUCAST reference methodologies yield the most reliable results, they are labor-intensive and impractical for routine clinical laboratories, which often rely on commercial assays such as Vitek 2, Sensititre YeastOne (SYO), and Etest¹⁸. Despite its convenience, SYO has notable limitations in testing C. auris. Studies demonstrate that SYO frequently overestimates amphotericin B resistance when colorimetric MICs are interpreted according to the provisional the Centers for Disease Control and Prevention breakpoint of 2 mg/L. Compared with the CLSI reference method, SYO produced MICs one to two dilutions higher, resulting in major error rates of up to 89%¹⁹. Reliable AFST is essential for guiding antifungal therapy, and amphotericin B MICs should preferably be determined using reference methods. When identification results are uncertain, additional confirmatory approaches are warranted. Matrix-assisted laser desorption ionization–time of flight mass spectrometry has demonstrated high accuracy for the identification of C. auris²⁰.

According to published reports, the fluconazole resistance rate of C. auris in China was 98.72% (308/312) [8]. The MIC values for 5-flucytosine were all < 0.25 µg/mL, and the resistance rate to amphotericin B was 4.17% (13/312)⁸, In this study, the fluconazole resistance rate of C. auris isolates from the hospital was 77.42%, and the resistance rate to amphotericin B was 3.23%, which are slightly lower than those reported in the literature. This discrepancy may be related to regional differences within China, given its vast geographic range and north-south variations. The increasing prevalence of infection caused by non-albicans Candida species is associated with the widespread use of prophylactic antifungal agents such as fluconazole²¹, however, the emergence of C. auris does not appear to be directly related to the overall antifungal drug usage in hospitals³, Therefore, further investigation is needed to understand the impact of antifungal drug use and stewardship on the susceptibility of C. auris. These findings also underscore the continuing critical role of infection control measures in preventing the nosocomial transmission of C. auris^22,23.

The risk factors for C. auris infection are similar to those associated with infections caused by other Candida species²⁴, approximately 10% of patients colonized with C. auris develop invasive infections, particularly those in intensive care unit settings who require mechanical ventilation and have invasive devices in place^12,13,25,26. The crude mortality rate of C. auris infection ranges from 0% to 72%²³. This study also found that the mortality rate associated with C. auris was higher than that of other Candida species. Therefore, strategies to prevent the nosocomial transmission and outbreak of C. auris infections in hospitals must be established^27–29. These include identifying patients with C. auris infection or colonization, implementing surveillance and reporting systems for C. auris infections, and performing species-specific identification of Candida isolates from sterile body fluids in all suspected invasive infection cases. Microbiology laboratories should promptly report findings to the hospital infection control department or the designated infection management team, as well as provide feedback to the attending physicians. Upon receiving such reports, the infection control department should conduct epidemiological investigations and implement contact isolation measures to prevent further transmission^30,31. Active screening and isolation should be conducted for patients with a history of close contact with C. auris, as well as for patients and their close contacts or suspected colonized individuals in facilities with a high number of C. auris cases. Screening should include sites such as the axilla, groin, and other relevant locations (e.g., urine, throat, wounds, and catheters)¹⁵. Patients with C. auris infection or colonization should be isolated in single rooms with dedicated bathrooms whenever possible. Alternatively, patients infected or colonized with the same organism may be cohorted in multi-bed rooms. Group nursing care, similar to that used for patients with carbapenem-resistant Enterobacteriaceae infection or colonization, is also recommended. Due to the slow growth and low sensitivity of traditional culture methods, PCR-based assays or metagenomic next-generation sequencing techniques can be employed when available^32,33. Regular assessment of colonization and decolonization status in C. auris patients is recommended. Some reports indicate that twice-daily skin decolonization using disposable towels (wipes) soaked in 2% chlorhexidine gluconate or 4% chlorhexidine solution can reduce colonization. For patients on mechanical ventilation, oral rinsing with 0.2% chlorhexidine may also contribute to decolonization to some extent¹².

Due to biofilm formation, C. auris can survive on various environmental surfaces for several weeks and has been isolated from healthcare workers’ hands, nasal cavities, and groin areas. This may serve as a source of transmission to other hospitalized patients³⁴. Therefore, healthcare workers must strictly adhere to hand hygiene protocols and use appropriate personal protective equipment. Isolation gowns should be worn during invasive procedures, extensive patient contact (such as repositioning or bathing patients), or when handling patient excreta. Visitors should also follow corresponding isolation measures, including wearing gowns, performing hand hygiene, and wearing gloves. Routine cleaning and disinfection of the environment and surfaces should be performed at least twice daily. Since quaternary ammonium disinfectants (e.g., benzalkonium chloride) have limited efficacy against C. auris, chlorine-based disinfectants at a concentration of ≥ 1000 mg/L should be used 2–3 times daily for effective decontamination³⁵. However, high concentrations of chlorine-based disinfectants can be irritating and may cause corrosion of medical instruments and equipment^36,37.

This study has several limitations that should be acknowledged. First, this study did not analyze the antifungal susceptibility of C. auris to micafungin and anidulafungin. Due to their favorable safety profile and efficacy, echinocandins have become the first-line treatment option for C. auris infections³⁸. The hospital is currently advancing and improving echinocandin susceptibility testing, with further analysis and research planned. Second, this study did not investigate the relationship between resistance trends in other Candida species and C. auris, which warrants further investigation in future studies. Third, we acknowledge that the relatively small number of C. auris cases included and the absence of molecular epidemiology limit the depth and generalizability of our analyses. Nevertheless, given that C. auris has only recently emerged in our region, systematically documenting its clinical characteristics, antifungal susceptibility patterns, and patient outcomes provides timely and clinically meaningful insights. To the best of our knowledge, this study represents one of the first observational reports on C. auris infections from our institution, thereby contributing to the limited evidence available nationally. We have highlighted this limitation in the manuscript and underscore the need for future multi-center and longitudinal studies to further validate and expand upon our findings. Fourth, due to hospital data confidentiality and the need for additional ethical approval, AFST data for other Candida species and detailed data regarding antifungal therapy, including the specific agents administered, timing of initiation, duration of treatment, and appropriateness of therapy could not be obtained and were therefore not included in the analysis and this limitation may restrict the generalizability of the study findings. Fifth, device-related infections were reported only in aggregate, without breakdown by type, duration, or removal, and future multi-center studies or those with more comprehensive datasets could offer more detailed analyses and deeper clinical insights. Sixth, diagnosis of pneumonia was based on clinical and microbiological data and was not confirmed by histology of lung tissue. Finally, antifungal susceptibility testing was performed by commercial methods.

Conclusion

In conclusion, the number of reported C. auris infection cases in China has been increasing. Vigilance is particularly warranted for fluconazole-resistant C. auris isolates. The implementation of effective hospital infection control measures is essential, including enhanced environmental surveillance and disinfection, strict adherence to hand hygiene protocols, and judicious use of antifungal agents to avoid unnecessary exposure to broad-spectrum antifungals that may contribute to resistance. In addition, healthcare personnel should receive targeted training to improve their ability to identify and manage C. auris infections. Through the comprehensive application of these preventive strategies, the risk of C. auris transmission can be significantly reduced, thereby improving healthcare quality and ensuring patient safety.

Author contributions

T.F.: Writing-review and editing, supervision, resources, project administration, methodology, conceptualization. Z.L.: Writing-original draft, investigation, formal analysis, data curation. Z.Z.: Writing-original draft, investigation, formal analysis, data curation. B.L.: Formal analysis, data curation. C.F.: Formal analysis, data curation. G.L.: Formal analysis, data curation. C.F.: Formal analysis, data curation. T.W.: Formal analysis, data curation. M.Y.: Formal analysis, data curation. Y.L.: Formal analysis, data curation. M.L.: Formal analysis, data curation. G.L.: Writing-review and editing, supervision. All authors reviewed the manuscript.

Funding

This project was supported by a grant from the Medical Research Fund Directive Project of Guangdong Provincial, China (C2024027).

Data availability

The original contributions presented in the study are included in the article material, further inquiries can be directed to the corresponding author.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval

All methods in this study were carried out in accordance with relevant guidelines and regulations. The study was approved by the Ethics Committee of The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China (Approval No. 2025-KY-KZ-108-01). Due to the retrospective nature of the study, the Ethics Committee of The Affiliated Guangdong Second Provincial General Hospital of Jinan University waived the need of obtaining informed consent and the use of a de-identified database.