Correction: Urinary tract infection caused by rare yeast Vanrija humicola in a urothelial carcinoma patient: a case report and literature review

Bladder cancer ranks as the ninth most common cancer worldwide, and its incidence continues to increase globally (1). Urothelial carcinoma is the most common histological type of bladder cancer, and cigarette smoking is a well-known major risk factor (2). Urothelial carcinoma of the bladder (UCB) is more common in men than in women, with a ratio of about 3-4:1. The highest number of cases occurs in people aged 85-89, while mortality rates are higher in those over 95 years of age (3). Transurethral resection of bladder tumors (TURBT) is the main method used to diagnose and stage bladder cancer. Treatment usually involves platinum-based chemotherapy and immunotherapy (4,5). Bladder cancer patients are also at high risk of secondary infections because of invasive medical interventions such as catheterization and surgery. About 22% of patients develop urinary tract infections (UTIs) after bladder tumor surgery (6).UTIs are mainly caused by Gram-negative bacteria, with Escherichia coli being the most frequent pathogen (7,8). Recently, fungal infections have also become increasingly common in immunocompromised cancer patients (9). Studies indicate that fungi can significantly influence the tumor microenvironment, affecting cancer development and progression (10). In cancer patients, Candida and Aspergillus species remain the leading causes of invasive fungal infections (IFIs), with an increasing incidence of rare fungal species being reported (11). Infections caused by rare fungi are challenging to diagnose and may delay the initiation of targeted antifungal therapy (12).Vanrija humicola (formerly Cryptococcus humicola) is a basidiomycetous yeast within the family Trichosporonaceae and the order Trichosporonales, a group phylogenetically related to Trichosporon species (13). These environmental yeasts are considered opportunistic pathogens, often colonizing catheters in immunocompromised patients and causing UTIs following urinary tract instrumentation (14). Here, we report a case of UTI caused by V. humicola in a patient with UCB. This report highlights the pathogenic potential of this rare opportunistic fungus in high-risk populations and discusses its diagnosis, treatment, and possible sources of infection.The patient is an 82-year-old male with a history of coronary heart disease. He underwent coronary artery bypass grafting (CABG) 5 years ago and has been on long-term antiplatelet and lipid-lowering therapy (clopidogrel, aspirin, atorvastatin). He had a 30-year history of heavy smoking (three packs/day) but quit over 20 years ago. He reported no alcohol use or family history of cancer.He complained of frequent, urgent, and painful urination accompanied by pain in the left hip joint and thigh for more than one month. Oral analgesics taken by the patient provided no relief, and he presented to a municipal local hospital on September 20, 2025. MRI revealed significant prostatic enlargement and a soft-tissue mass in the left iliac bone; however, no treatment was administered.Subsequently, the patient visited Jiangxi Cancer Hospital on September 22, 2025. On admission, his vital signs were stable (temperature 37.1 °C, heart rate 104 bpm, blood pressure 133/65 mmHg). Physical examination was unremarkable, with no palpable lymphadenopathy and normal cardiovascular, respiratory, abdominal, and neurological findings. Chest and abdominal CT, along with a whole-body bone scan, revealed a subpleural nodule in the right middle lobe. Scattered small nodules were also seen in both lungs. In addition, osteolytic bone destruction was detected, with abnormal radionuclide uptake in the left ilium, acetabulum, and ischium, accompanied by a localized soft-tissue mass. Urinalysis showed gross hematuria, marked elevations in protein, red blood cells (RBCs), and white blood cells (WBCs). Based on these findings, the clinicians initially suspected prostate cancer with pulmonary and bone metastases, complicated by a UTI. Empiric intravenous anti-infective therapy with cefoperazone-sulbactam was then initiated at a dose of 3.0 g every 12 hours.The patient underwent transurethral plasmakinetic resection of the prostate (TUPKP)to relieve urinary tract obstruction and obtain tissue for definitive pathological diagnosis. Intraoperatively, extensive bleeding was observed on the prostatic surface. A cauliflowerlike tumor was also identified at the bladder neck, protruding into the bladder lumen. It showed invasion of both the bladder wall and the prostate. The procedure was uneventful, with an estimated blood loss of approximately 5 mL, and no blood transfusion was required. The resected prostatic tissue was sent for histopathological examination and immunohistochemical staining. The final diagnosis confirmed a malignant bladder tumor, specifically urothelial carcinoma (AJCC stage M1 IV). There was secondary malignant involvement of the prostate, along with metastases to the lungs and bones. After surgery, the patient experienced recurrent hematuria, which was attributed to postoperative surgical trauma. In response, intravenous cefotiam hydrochloride was initiated at a dose of 1.0 g every 8 hours as anti-infective therapy.During treatment, a urine sample was collected on October 9, 2025, due to persistent hematuria and pyuria, along with ongoing suspicion of UTI despite empirical antibiotic therapy (Table 1). This sample was sent for both bacterial and fungal culture before the initiation of radiotherapy and chemotherapy. Given the advanced stage of disease and persistent left hip pain, palliative radiotherapy was initiated on October 10, 2025. A total dose of 30 Gy was delivered in 10 fractions, targeting the bladder, prostate, and left pelvic bones. On the same day, systemic treatment with chemoimmunotherapy was also started. The regimen included toripalimab (240 mg), gemcitabine (0.6 g), and cisplatin (30 mg). The urine culture grew Enterococcus faecalis on October 10 at a concentration of 5 × 10 4 CFU/mL. Fungal culture of the same urine specimen demonstrated heavy growth of an unidentified yeast (>10 5 CFU/mL) on October 12. The fungus produced moderately sized pink, dry, and cerebriform with a fringed margin colonies after incubation on Sabouraud Dextrose Agar-TTC medium at 28 °C for 72 hours. For species identification, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed; however, it failed to identify the organism at the species level in our case. In view of persistent fever and elevated inflammatory markers, molecular identification was subsequently performed. Sequencing of the internal transcribed spacer (ITS) region, together with the D1-D2 domain of the large subunit ribosomal DNA, identified the isolate as Vanrija humicola. The corresponding ITS sequence was deposited in the GenBank database under accession number PX850820. Based on these findings, the patient was diagnosed with a mixed urinary tract infection caused by Enterococcus faecalis and Vanrija humicola (Figure 1).Following antimicrobial susceptibility testing and multidisciplinary consultation, treatment was initiated with intravenous amoxicillin-clavulanate at a dose of 1.2 g every 8 hours from October 13, 2025, to October 16, 2025. Intravenous voriconazole was administered for antifungal therapy, based on its low MIC value (0.12 µg/mL) observed in our isolate. It was given at a dose of 0.2 g every 12 hours. Intravenous voriconazole therapy was administered from October 14 to October 15, 2025, and was resumed from October 17 to October 20, 2025. Therapeutic drug monitoring of voriconazole plasma levels was not performed during treatment. All antibacterial and antifungal therapies were administered exclusively through the intravenous route, with no switch to oral therapy during hospitalization. Urine parameters were closely monitored, and repeat cultures were performed during therapy to assess microbiological response. During treatment, the patient developed several manageable adverse effects. These included nausea, vomiting, and grade II myelosuppression. All of these events were controlled effectively with supportive care.After completing anticancer and antimicrobial therapy, urinary symptoms resolved, inflammatory markers normalized, and left hip pain improved. The patient was discharged on October 22, 2025.We report a case of UTI caused by V. humicola and E. faecalis in a patient with UCB. Human infections caused by V. humicola remain extremely uncommon. Most reported cases occur in immunocompromised patients. The first case was described in 1975 in patients presenting with conjunctivitis and ophthalmic disease (15). In cancer patients, the first report was published in 1998 from Mexico City, describing four cases (16). Another report described a systemic infection in a seven-year-old boy from India with suspected leukemia or lymphoma, from whom isolates were recovered from both blood and urine (17). Reported clinical manifestations are predominantly urinary tract infections, including cases in cancer patients and in individuals with a history of multiple invasive procedures (Table 2) (14,18). In contrast, V. humicola has also been detected in respiratory samples from four cystic fibrosis patients (20). These findings suggest that V. humicola may act as an opportunistic organism in healthcare settings, particularly among immunocompromised patients, rather than being solely an environmental contaminant.Opportunistic fungal infections are an emerging concern in cancer patients. Several major risk factors have been identified, including prolonged neutropenia, intensive chemotherapy, corticosteroid therapy, disruption of mucosal barriers, prolonged antibiotic exposure, and hospital-related factors such as invasive procedures (21)(22)(23)(24)(25). In the present case, multiple factors may have contributed to the development of opportunistic fungal infection. First, advanced urothelial carcinoma itself may disrupt the urinary tract mucosal barrier and compromise host immunity. Second, the patient underwent TUPKP, and postoperative hematuria was observed. We speculate that the invasive nature of the surgical procedure may have damaged the urinary tract mucosa. Postoperatively, the patient received a three-lumen urethral catheter and a drainage tube, which also created favorable conditions for fungal infection. Subsequently, the patient received chemotherapy and immunotherapy, which may have resulted in myelosuppression and consequently weakened the host's immune defense. In addition, advanced age, empirical broad-spectrum antibiotics, and concomitant bacterial infection may act as additional contributing factors for fungal colonization and infection. Bacterial infection can alter the urinary microbial ecosystem, potentially creating conditions that allow opportunistic fungi to proliferate. Our case supports the observation that disruption of the urinary mucosal barrier and changes in the local microbial ecological niche may create an environment for colonization and infection of rare environmental yeasts (14). From a pathobiological perspective, the urinary microbiome and mycobiome are increasingly recognized as playing important roles in the development of urothelial cancer and modulating responses to treatment (26). An important consideration in the present case was differentiating infection from colonization. The rare environmental yeasts recovered from urine may occasionally represent transient contamination or asymptomatic colonization (27). However, in our case, several findings supported clinically significant infection rather than colonization. These included persistent urinary symptoms, fever, marked pyuria, elevated inflammatory markers, heavy fungal growth (>10 5 CFU/mL) in urine culture in the setting of advanced malignancy, recent urinary tract surgery, chemo-immunotherapy, and prolonged hospitalization. In addition, the patient showed clinical improvement after initiation of voriconazole therapy, with resolution of urinary symptoms and normalization of inflammatory markers. These overall clinical and microbiological findings suggested that V. humicola acted as an opportunistic urinary pathogen in the current case.In both clinical and laboratory settings, accurate identification of rare fungi remains challenging. The accuracy of phenotypic identification methods ranges from approximately 63.3% to 76.7% (19). MALDI-TOF-MS has emerged as a powerful tool for the identification of rare fungi, with reported identification accuracy exceeding 90%; however, its performance is highly dependent on the coverage of the reference database (28). A study from Korea reported successful identification of V. humicola using the Bruker Biotyper MALDI-TOF MS system, indicating that accurate identification is achievable when the reference database is sufficiently populated (14). Nevertheless, identification of V. humicola and other rare fungi by MALDI-TOF-MS remains variable and may fail in settings with limited database representation. The ITS region, which has been designated by mycologists as the universal DNA barcode for fungi, plays a critical role in species-level identification (29). In the present case, molecular sequencing of the ITS region and the D1-D2 domain of the large subunit rDNA, followed by phylogenetic analysis, was essential for accurate species identification. Previous studies have suggested that using MALDI-TOF-MS or updated high-throughput platforms as rapid identification tools is useful. Sequencing (ITS/D1-D2) can then be used for further confirmation, which may be the best practice for identifying rare fungal isolates (30)(31)(32)(33). Furthermore, because it can be misidentified as non-neoformans Cryptococcus or Candida species, special caution is required. Whenever a yeast shows phenotypic characteristics inconsistent with patient symptoms or antifungal susceptibility testing (AST), molecular identification should be prioritized (34). Rare yeasts often exhibit elevated minimum inhibitory concentrations (MICs) to azoles and/or echinocandins, whereas the activity of amphotericin B generally remains relatively stable (35)(36)(37)(38). Many rare yeasts, including V. humicola, currently have no breakpoints defined by either the Clinical and Laboratory Standards Institute (CLSI) or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Therefore, antifungal therapy should be guided by both species identification and MIC values, rather than relying only on empirical treatment, because antifungal susceptibility can vary widely among different taxa (39,40). In the present case, AST was performed before definitive species identification. The isolate demonstrated elevated MIC values for echinocandins but lower MICs for azoles and amphotericin B. The MIC against amphotericin B was <1 mg/L, consistent with previously reported studies (14,20). The elevated MIC to echinocandins in our case is similar to the study reported from Korea, but it is different from the four isolates reported from sputum samples in Poland, which had MICs of <1 mg/L in all isolates (14,20). Regarding azole drugs, the current strain had lower MICs than previously reported strains. For fluconazole, the MIC of the current strain was 4 mg/L, while it was >64 mg/L in strains reported in Korea. In the strains isolated in Poland, one isolate had an MIC of 2 mg/L, and the other three had MICs of >32 mg/L. Similarly, the voriconazole MIC of the strains from Korea was 2 mg/ L, while the strains from Poland had MICs of <1 mg/L for two isolates and >32 mg/L for the other two (14,20). In our case, the MIC for voriconazole was 0.12 mg/L, indicating good in vitro susceptibility. In the present case, amphotericin B was not favored because of its known nephrotoxicity and infusion-related adverse effects, which are of particular concern in elderly patients with advanced malignancy and multiple comorbidities (41,42). Although itraconazole and posaconazole are active against some yeasts, their oral absorption and plasma exposure may be variable, and their intravenous formulations have limitations in routine initial use (43,44). Fluconazole showed higher MIC values than voriconazole in this isolate, suggesting weaker in vitro activity. By contrast, voriconazole has predictable intravenous administration, established use in invasive fungal infections, and a much lower MIC in this case. Therefore, voriconazole therapy was started, and the patient responded well to the treatment, highlighting the importance of MIC testing for timely and appropriate antifungal therapy. In previously reported cases, two infected patients were treated with voriconazole and caspofungin, respectively (14). The current case, together with previous reports, suggests that because MIC values differ among cases, antifungal susceptibility-guided therapy should be prioritized for the treatment of V. humicola infection. However, patient risk factors, infection site, and the distinction between colonization and invasive disease should also be considered when selecting therapy. Empirical treatment with an azole or amphotericin B may be reasonable while awaiting definitive laboratory results.Furthermore, this study also reinforces that rare environmental fungi can cause clinically significant infections in immunocompromised patients, particularly when intensive medical care and invasive procedures are involved. We agree that V. humicola should be regarded as a potential nosocomial urinary tract pathogen, while also recognizing that it may act as a urinary colonizer. Further investigations integrating comprehensive clinical characterization with high-resolution molecular approaches are warranted. Such studies may help determine whether V. humicola contributes directly to cancer-related processes or primarily acts as an opportunistic pathogen or colonizer in immunocompromised hosts.This case, together with the literature review, demonstrates that environmental fungi like V. humicola can cause opportunistic infections in severely immunocompromised cancer patients. Timely identification and confirmation of rare pathogens using molecular methods are important for accurate diagnosis. The current isolate and literature indicate that V. humicola has high MICs to echinocandins, low MICs (<1) to amphotericin B, and variable MICs to azoles. AST and MICguided therapy are essential to improve clinical outcomes. Future molecular studies with detailed clinical data are needed to determine whether V. humicola affects cancer-related processes or just represents an environmental contaminant.The requirement for written informed consent was waived by the Institutional Ethics Committee because no identifiable patient information is included in this case report. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.