Candiduria is a condition characterized by the presence of Candida in the urine and is most common in hospitalized patients, with a prevalence of approximately 10-15%.² Candida UTIs in hospitals are most commonly found in patients using urinary catheters and in those treated in intensive care units.² Some risk factors for candiduria include age, female, diabetes mellitus, prolonged hospitalization, treatment in the intensive care unit, immunosuppressive therapy, use of broad-spectrum antibiotics, history of previous surgery (urological and non-urological), radiation therapy, genitourinary tuberculosis, neutropenia, and use of urinary tract instrumentation.¹²

In this study, most patients were younger than 60 years of age, and the average age was 53 years, with a higher proportion of women than of men (80.77% vs. 19.23%, respectively). However, the results of the correlation analysis of age and sex showed no statistically significant correlation between age (p = 0.886) and sex (p = 0.107) with the incidence of Candida UTIs. This may indicate that age and sex are risk factors for candiduria but not for Candida UTIs. In other studies, Candida was found to be more common at ages of less than 15 and >46 years. This is because the host defense is lower at extreme ages.¹³ Further, the presence of a shorter urethra and colonization of Candida species in the vulvo-vestibular region, which occurs mostly in women, increase the risk of ascending candiduria.¹⁴

Another study related to urinary catheter use and biofilm formation, conducted in Indonesia in 2017-2018, showed that the two risk factors influencing biofilm formation were female sex and duration of urinary catheter use (p < 0.05). Further, urinary catheter use for five or more days resulted in a higher biofilm mass than that with a shorter duration of catheter use.¹⁵ In this study, a second urine specimen could be immediately collected for patients who used a urinary catheter for up to 5 days, but a urinary catheter was used for more than the 5 days, the catheter was replaced before repeat collection of the urine specimen. This measure was applied to reduce the risk of biofilm formation. The prolonged use of a urinary catheter in the bladder can cause yeast and pseudohyphae to adhere to the urinary catheter, which can cause persistent candiduria and false-positive results; therefore, the replacement of a urinary catheter can provide resolution in some cases of candiduria.¹⁶ Urinary tract infections caused by Candida occur most often in the ascending regions related to urinary catheter use. A urinary catheter can be a portal for the entry of microorganisms into the urinary tract and can also be a place for microorganisms to colonize if used for a long time.¹²

Candiduria can be detected in outpatients at 0.11-0.75% and significantly higher in inpatients at 3.49-10.63%.⁶ In this study, candiduria was found in 59.62% of patients admitted to the intensive care unit (31 of 52 patients), and Candida UTIs accounted for 87% (27 of 31 patients). This shows that more than half of the patients with candiduria who had clinical symptoms of UTIs were admitted to the intensive care unit, which could increase the mortality rate of these patients if antifungal therapy was not administered. Candiduria is an indicator of invasive candidiasis, which can be serious, particularly in immunocompromised patients.¹⁷ In a prospective multicenter study, the incidence of candiduria was 22% in critically ill patients treated in the intensive care unit for >7 days. This may occur because patients with candiduria experience high antimicrobial exposure during treatment in the intensive care unit.¹⁴

Diabetes mellitus is a metabolic disorder that predisposes individuals to fungal infections, including Candida species, owing to its immunosuppressive effect in patients.¹⁸ In addition, diabetes mellitus is a predisposing factor for candiduria and Candida UTIs.¹⁹ In this study, 63.46% (33 of 52 patients) of patients with candiduria had diabetes mellitus while  84.37% (27 of 32 patients) of the patients Candida UTIs had diabetes mellitus. In this study, statistical analysis showed no correlation between diabetes mellitus and the incidence of Candida UTIs (p = 0.826); this could be attributed to the lack of data related to the duration and status of diabetes mellitus. Diabetes mellitus is a risk factor for asymptomatic candiduria; however, the occurrence of infection is also influenced by the duration of diabetes mellitus and glycemic control.

The presence of glucose in blood and the secretion of degrading enzymes can generally cause immunosuppression in patients, which can cause an imbalance between the host and yeast resulting in Candida transitioning from commensal to pathogenic and causing an infection.¹⁸ The presence of urogenital infections caused by Candida species is expected to become more widespread in patients with diabetes, especially in those with poor glycemic control. In patients with diabetes, disease duration and long-term poor glucose regulation alter the renal microvasculature and frequent polyuria/glycosuria, which may lead to more frequent urinary tract infections.¹⁷

The prevalence of candiduria in patients with a history of antibiotic use at Dr. Soetomo General Academic Hospital in Surabaya was 81.4%.⁵ In this study, patients with candiduria who previously used antibiotics constituted 98% (51 of 52 patients) of which 84.3% (43 of 51 patients) had UTIs due to Candida. The results of the correlation test showed a correlation between the previous use of antibiotics and incidence of UTIs caused by Candida (p = 0.027*). In a case-control study, the number of patients with candiduria increased 12-fold after the use of a urinary catheter, 6-fold after the use of broad-spectrum antibiotics, 6-fold in the presence of urinary tract abnormalities, and 2-fold in the presence of diabetes mellitus.²⁰

Previous antibiotic use is a risk factor for UTIs due to Candida, and contributes to Candida colonization by suppressing normal bacterial flora, especially in the gastrointestinal tract, lower genital tract, and perineum. This can cause Candida overgrowth, allowing it to enter the urethra and colonize or infect the bladder.¹⁴ Further, antibiotics can interfere with phagocyte function and antibody formation, leading to impaired host defense mechanisms against Candida infection.²¹

The presence of candiduria triggers physicians to consider whether the patient has a urinary tract infection caused by Candida species or just bladder colonization or contamination²² A repeat urine specimen is used to confirm whether candiduria is caused by contamination, colonization, or infection. If the patient has a urinary catheter, urine specimen collection is repeated after urinary catheter replacement.⁸ Thus, a second urine specimen is obtained to verify the patient’s condition and to determine whether antifungal therapy or elimination of predisposing factors such as urinary catheter replacement is needed.

UTIs are divided into two parts (lower and upper tract infections), which can be caused by fungi or bacteria and can be symptomatic or asymptomatic.²³ Most symptomatic Candida UTIs develop as ascending infections that start in the lower urinary tract with the same pathogenesis as that of bacterial UTIs. Patients with ascending infections may present with cystitis or pyelonephritis.²²

Symptomatic candiduria has been observed in patients with cystitis, epididymoorchitis, prostatitis, pyelonephritis, and renal candidiasis.²³ In contrast, in patients with asymptomatic candiduria, the presence of Candida in the urine may represent colonization and elimination of risk factors such as urinary catheter use is the recommended therapy.²²

In a previous multicenter study, only 4% of patients with candiduria were asymptomatic, and in a smaller study, 14% of symptomatic patients had UTIs.²⁴ In another prospective study, 2-4% of patients with candiduria had one of the symptoms of urinary tract infection.⁷ In this study, the prevalence of asymptomatic candiduria was 11.54% (6 of 52 patients), and that of symptomatic candiduria was 82.69% (43 of 52 patients); the statistical analysis results showed a significant correlation between candiduria and the incidence of UTIs because of Candida (p = 0.000*). The high prevalence of UTIs due to Candida in this study could be attributed to the inclusion of patients who were suspected by clinical doctors of having UTIs. Most of the study sample included patients who were admitted to the intensive care unit, used urinary catheters, had diabetes mellitus, and had previous antibiotic use, which are risk factors for Candida becoming a pathogen and causing an infection. This is supported by the results of previous studies, which reported an increase in the incidence of Candida infection in immunocompromised patients, especially those with diabetes mellitus.¹⁹ Further, the use of broad-spectrum antibiotics can decrease the number and function of commensal bacteria, which can increase the colonization of pathogenic microorganisms.¹⁸

In this study, the number of Candida colonies was determined to be ≥10³ to ≥10⁵ CFU/ml in patients with and without urinary catheter use; the statistical results showed no correlation between the number of colonies being >10⁵ or <10⁵ CFU/ml and the incidence of UTIs caused by Candida (p = 0.248). In this study, 16.3% (8 of 49 patients) of patients with Candida colony counts <10⁵ CFU/ml were found to have UTIs due to Candida. Further, 14.6% (6 of 41 patients) had Candida colony counts >10⁵ CFU/ml, but did not have Candida UTIs. This could be because these patients used a urinary catheter for more than two days; notably, using a urinary catheter is a risk factor for Candida colonization, which results in high colony counts, but lack of clinical symptoms in patients. This shows that the number of Candida colonies cannot be a reference for determining the presence of a UTIs due to Candida, but need a clinical data of the patients.

Urinary catheter can cause mechanical damage to the bladder and lead to the release and accumulation of fibrinogen in the bladder and the urinary catheter. A fibrinogen-coated urine catheter is a site for the attachment Candida albicans, resulting in a strong biofilm consisting of yeast, pseudohyphae, and hypha. Therefore, the attachment of fibrinogen and Candida albicans can cause bladder colonization and UTIs associated with urinary catheters.²⁵

Another study showed that in patients without urinary catheters, Candida colony counts <10⁴ CFU/ml in urine were correlated with the presence of renal infection. However, in patients with urinary catheters, there was no correlation between lower Candida colony counts and renal involvement, whereas colony counts ≥10⁵ CFU/ml showed no evidence of UTIs caused by Candida.²⁶ Another study also showed that the use of urinary catheters significantly led to bladder colonization by all Candida strains up to ≥10⁵ CFU/ml, whereas with no urinary catheters, colonization by all Candida strains was significantly lower at ≤10³ CFU/ml.²⁵

Direct microscopic examination of urine specimens can be done using Gram staining. If yeast, pseudohyphae, or hyphae are found, the UTI may be caused by Candida.²⁷ Urine specimens in this study were Gram-stained and observed directly microscopically. The results revealed yeast, pseudohyphae, or hyphae in 88.46% (46 of 52 patients) of candiduria cases, of which 86.9% (40 of 46 patients) were UTIs caused by Candida. The results of the correlation analysis showed a correlation between the discovery of yeast, pseudohyphae, or hyphae from Gram staining and the incidence of UTIs due to Candida (p = 0.024*). Thus, presence of yeast, pseudohyphae, or hyphae in Gram staining along with clinical symptoms can be an early sign of UTIs due to Candida.

A previous study at Dr. Soetomo Hospital identified nine different Candida species in patients with candiduria: Candida albicans (42.7%; n = 79), Candida tropicalis (31.4%; n = 58), Candida glabrata (10.8%; n = 20), Candida parapsilosis (10.3%; n = 19), Candida rugosa (2.2%; n = 4), Candida krusei (1.1%; n = 2), Candida lipolytica (0.5%; n = 1), Candida guilliermondii (0.5%; n = 1), and Candida lusitaniae (0.5%; n = 1).⁵ Candida albicans is the most commonly isolated yeast from urine, accounting for 50-70% of the isolates in various studies. Candida glabrata and Candida tropicalis are the next most common species found in urine cultures.²⁴ In line with the results of this study, Candida albicans 20 (38.46%) was identified as the most common cause of candiduria, followed by Candida tropicalis in 19 (36.54%), Candida glabrata in 5 (9.62%), Candida parapsilosis in 4 (7.69%), and Candida krusei in 1 (1.92%). In the present study, Candida tropicalis was the most commonly isolated Candida species from patients with diabetes mellitus.

Candida albicans, which is a commensal microorganism on the skin and mucosal surface and can be an opportunistic pathogen of the genitourinary system, remains the most common cause of candidiasis.¹⁷ Non-albicans Candida is also emerging as a pathogen that can colonize mucosal surfaces.⁸

A limitation of this study was that it could not determine the pathogenesis of Candida UTIs, whether ascending or descending, because no fungal culture of blood specimens was performed to detect the presence of candidemia in patients with Candida UTIs. However, as the urine specimens were re-collected, so the pre-analytical process could be maintained according to the standards set for the study. Further, repeat specimens were collected from patients with candiduria to confirm whether candiduria was caused by colonization or a pathogen causing Candida UTIs. In this study, urinary catheters were also replaced if they had been used for more than five days; this was done to prevent Candida colonization in the urinary catheters.