Urinary tract infections (UTIs), second only to respiratory infections in prevalence, are a common clinical concern. Among these, Candida species, opportunistic pathogens, pose a significant threat to hospitalized patients and those with weakened immune systems. With the widespread use of broad-spectrum antibiotics and immunosuppressive therapies, the incidence of Candida UTIs is on the rise globally. This highlights the need for vigilant prevention, monitoring, and meticulous nursing care, especially for high-risk patients with prolonged hospitalization, catheter use, comorbidities, and compromised immunity.
Candida species are now responsible for approximately 10% of urine culture-positive cases, with a notable shift towards non-Candida albicans species. This shift is not merely a change in pathogen types but a complex issue that exacerbates global antifungal resistance through intricate drug-resistant mechanisms and strong environmental adaptability. Treatment options are limited by the toxicity and pharmacokinetic constraints of antifungal drugs, and the emergence of antifungal resistance further complicates therapeutic strategies. Therefore, continuous surveillance of species distribution and antifungal resistance patterns is crucial for informed clinical decision-making, yet research in this area remains limited.
To address this gap, our study presents a comprehensive five-year retrospective analysis of Candida UTIs in a tertiary hospital in Beijing. By examining the long-term dynamic evolution of strain distribution and drug resistance, we aim to reveal the distribution of species, trends in antifungal resistance, and associated clinical risk factors for Candida UTIs in this region. These findings will serve as a crucial basis for formulating personalized empirical treatment schemes tailored to local resistance patterns.
Methods:
Clinical Data Collection:
A retrospective analysis was conducted on 229 patients diagnosed with Candida urinary tract infections (UTIs) at our hospital between 2020 and 2024. The study protocol was approved by the Ethics Committee of the Third Medical Center of the Chinese PLA General Hospital, and informed consent was obtained from all participants. Patients included in the study met three criteria: microbiological confirmation of Candida at concentrations >1×105 CFU/mL from midstream urine samples, abnormal urinalysis results (positive leukocyte esterase, nitrite, or pyuria, along with yeast-like spores observed during urine microscopy), and clinical symptoms consistent with UTI (lower urinary tract symptoms or systemic symptoms without another identifiable source of infection). Exclusion criteria included repeated isolation of the same Candida strain from the same patient and incomplete demographic or antifungal susceptibility testing data.
Microbiological Methods:
Strain Isolation and Identification:
Midstream morning urine samples were aseptically collected from patients using sterile catheters. A 5μL aliquot of urine was inoculated onto ChromAgar medium and incubated aerobically at 37°C for 24–48 hours. Preliminary species identification was based on colony color and morphology on ChromAgar, with further analysis using the VITEK 2 COMPACT system for strains that could not be conclusively identified via chromogenic reaction.
Antifungal Susceptibility Testing:
Antifungal susceptibility testing was performed using the ATB FUNGUS 3 broth microdilution method, testing fluconazole, voriconazole, itraconazole, amphotericin B, and 5-fluorocytosine. The minimum inhibitory concentration (MIC) for each drug was determined visually, and isolates were assigned to susceptibility categories (S or R) based on Clinical and Laboratory Standards Institute breakpoints. Candida albicans ATCC 14053 served as the quality control strain.
Statistical Analysis:
Statistical analyses were conducted using SPSS version 27.0. Categorical variables were expressed as frequencies and percentages, and intergroup comparisons were made using the chi-square (χ2) test. Multivariate logistic regression analysis identified independent risk factors associated with Candida UTIs.
Results:
General Information:
Between 2020 and 2024, 230 Candida strains were isolated from 229 patients, including 138 males and 91 females. The average age of male patients was 72.20 ± 15.87 years, and female patients was 72.27 ± 18.92 years, with no statistically significant differences in gender or age distribution (P > 0.05). This demographic stability over time is crucial for subsequent analysis.
Isolation of Candida:
During the study period, 230 Candida strains were isolated, with annual distributions as follows: 34 strains (14.8%) in 2020, 52 (22.6%) in 2021, 44 (19.1%) in 2022, 49 (21.3%) in 2023, and 51 (22.2%) in 2024. C. albicans was the most common species, accounting for 118 strains (51.3%), while non-albicans species made up 48.7%, including 42 C. tropicalis, 33 C. parapsilosis, and 27 C. glabrata. Notably, the detection rate of C. albicans decreased from 47.06% in 2020 to 39.22% in 2024, while non-albicans Candida increased, posing clinical challenges in empirical treatment formulation.
Departmental Distribution:
Of the 230 Candida isolates, the highest proportions were from the Intensive Care Unit (25.22%) and the Department of Urology (16.96%), highlighting the increased risk of Candida infections in these settings.
Antifungal Susceptibility:
Overall Susceptibility Profile:
Antifungal susceptibility testing was performed on 199 strains due to patient discharge and incomplete data. All tested strains were fully susceptible to amphotericin B and 5-fluorocytosine (0.00% resistance). However, resistance to azole antifungals was higher: 26.63% for itraconazole, 17.59% for fluconazole, and 16.58% for voriconazole. Resistance rates varied significantly among Candida species.
Temporal Trends in Resistance:
Assessment of resistance trends in C. albicans and C. tropicalis from 2020 to 2024 revealed fluctuations in triazole resistance rates over time, but these variations were not statistically significant (P > 0.05). This indicates a relatively stable resistance of these Candida species to triazole drugs, but continuous monitoring is crucial to detect potential resistance turning points.
Factors Associated with Candida Urinary Tract Infections:
Significant differences were observed between patients with Candida UTIs and bacterial UTIs in terms of hospital stay duration, indwelling urinary catheter use, and broad-spectrum antibiotic administration (P < 0.05). Multivariate logistic regression analysis identified hospital stay duration (≥14 days) and indwelling urinary catheter use (≥7 days) as independent risk factors for Candida UTIs, while broad-spectrum antibiotic use did not retain statistical significance.
Discussion:
Candida species are increasingly important fungal pathogens in UTIs, particularly among immunocompromised patients, those with prolonged antibiotic exposure, or indwelling urinary catheterization. In immunocompromised hosts, Candida UTIs can lead to candidemia and systemic candidiasis, severe conditions with high mortality rates and significant healthcare costs. Early diagnosis and targeted antifungal therapy are pivotal for improving patient prognosis and reducing disease burden. While bacterial UTIs have been extensively studied, research on Candida UTIs is relatively limited. In our hospital, Candida is the fourth most common causative agent of UTIs, with high detection rates in intensive care and urology departments, likely due to the vulnerability of patients in these units.
Our five-year surveillance data revealed a decline in C. albicans detection and a corresponding increase in non-albicans species, aligning with previous studies. The high proportion of elderly patients (mean age 72.2 years) and prevalence of chronic comorbidities, including malignancy, diabetes, cerebrovascular disease, pneumonia, and cardiovascular disease, may contribute to the elevated detection rate of non-albicans Candida species. For symptomatic Candida UTIs, fluconazole is recommended as first-line therapy due to its excellent urinary excretion. However, our antifungal susceptibility testing revealed species-specific resistance patterns and year-to-year variability in susceptibility. While all isolates remained fully susceptible to amphotericin B and 5-fluorocytosine, resistance to azoles, particularly triazoles, was prominent.
C. albicans and C. parapsilosis exhibited relatively low azole resistance, but C. tropicalis showed significantly higher triazole resistance (P<0.05), likely due to its robust biofilm-forming capacity. The historically low detection of C. tropicalis may have led to its under recognition and the overuse of fluconazole as empirical therapy, facilitating the emergence of azole-resistant C. tropicalis strains. C. glabrata also displayed concerning itraconazole resistance (44.00%), consistent with findings from a tertiary care center in South India. This emphasizes the importance of species-level identification in managing Candida infections. Consequently, significant variation in susceptibility to triazole antifungal drugs existed among Candida species. Relying solely on empiric therapy may be ineffective and potentially exacerbate drug resistance. Obtaining species identification and antifungal susceptibility testing is imperative to guide targeted treatment.
Our analysis identified prolonged hospitalization (≥14 days) and long-term catheterization (≥7 days) as independent risk factors for Candida UTIs, corroborating previous studies. Extended hospital stays and indwelling urinary catheters disrupt the natural physical barrier and local mucosal immune microenvironment of the urinary tract, increasing the risk of Candida colonization and UTIs. In clinical practice, minimizing unnecessary urinary catheterization and closely monitoring infection-related indicators are critical to reducing Candida UTIs. Interestingly, the use of broad-spectrum antibiotics was not found to be an independent risk factor for Candida UTIs in our cohort, possibly due to sample size limitations.
This study had limitations, including the use of the ATB™ FUNGUS 3 system for antifungal susceptibility, which lacks echinocandin assessment, and the exclusion of some eligible patients from the drug resistance analysis. Future research should aim to expand the sample size, incorporate echinocandin susceptibility testing, and establish long-term resistance surveillance to provide comprehensive evidence for clinical treatment strategies.
In summary, our five-year analysis revealed an increasing prevalence of non-C. albicans species in Candida UTIs, with C. tropicalis showing notable azole resistance. Amphotericin B and 5-fluorocytosine remained viable treatment options. Risk factor analysis emphasized the critical role of hospitalization duration and catheter use in increasing susceptibility to Candida UTIs. Routine species identification and antifungal susceptibility testing are essential to guide tailored therapy, improve treatment efficacy, and alleviate patient burden. For high-risk patients or those with fluconazole-resistant infections, first-line therapy with echinocandins or amphotericin B is recommended, along with immediate involvement of infection control teams upon detection of rare or highly resistant strains. Future research should establish a multicenter prospective surveillance network to dynamically monitor regional antifungal resistance patterns and inform the development of localized, tailored empirical therapy strategies.