Candida glabrata is a species of yeast that has emerged as a significant cause of urinary tract infections (UTIs) in healthcare settings. Unlike Candida albicans, the most common fungal pathogen, C. glabrata is classified as a non-albicans Candida species and often possesses intrinsic resistance to standard antifungal treatments. This pathogen frequently affects high-risk individuals, including hospitalized patients, those with indwelling urinary catheters, or those who are immunocompromised. Specialized diagnostic and therapeutic approaches are required because typical treatments for bacterial UTIs or C. albicans infections are often ineffective.
How Candida Glabrata UTIs Are Identified
Identifying a C. glabrata UTI begins with a standard urine culture, which reveals the presence of yeast (candiduria). However, detecting yeast alone is often inconclusive, as it may represent simple colonization rather than a true infection, especially in catheterized patients. A laboratory technique called speciation must then be performed to precisely identify the yeast as C. glabrata, differentiating it from other Candida species.
Microscopic examination provides an early clue, as C. glabrata cells are typically smaller and do not form the branching structures called hyphae, unlike many other Candida species. Following speciation, Antifungal Susceptibility Testing (AST) determines how sensitive the specific C. glabrata isolate is to various medications. This susceptibility data is essential because treatment guidelines are heavily dependent on the organism’s resistance profile.
Factors Complicating Treatment
Treatment for C. glabrata UTIs is complex due to biological and patient-related factors. The yeast has intrinsic reduced susceptibility to fluconazole, the most common antifungal agent used for Candida infections. Approximately 30% of C. glabrata isolates exhibit resistance, necessitating alternative drug choices. Furthermore, the organism forms robust biofilms, particularly on indwelling urinary catheters.
These biofilms create a protective layer, shielding the yeast from immune cells and making it difficult for antifungal drugs to reach therapeutic concentrations. The affected patient population commonly has underlying conditions like diabetes mellitus, recent broad-spectrum antibiotic exposure, or compromised immune systems. These comorbidities increase infection risk and limit medication options due to toxicity or drug interactions.
First-Line Antifungal Treatment Options
First-line treatment for C. glabrata UTI is guided by antifungal susceptibility testing (AST). If the isolate is susceptible to fluconazole, it remains a viable option due to its excellent concentration in the urine. For symptomatic cystitis caused by a susceptible strain, the recommended regimen is 200 mg daily for two weeks. Physicians may use a higher dose, such as 400 mg daily, to ensure adequate drug exposure in the urinary tract, especially for susceptible C. glabrata.
When the C. glabrata isolate is resistant to fluconazole, alternative agents must be employed according to established guidelines. Amphotericin B deoxycholate is a common second-line choice, administered intravenously at 0.3 to 0.6 mg/kg daily for one to seven days. Only the deoxycholate formulation is recommended for UTIs, as lipid formulations do not achieve sufficient effective concentrations in the urine.
Oral flucytosine is another effective alternative for resistant organisms, given at 25 mg/kg four times daily for seven to ten days. Flucytosine is highly concentrated in the urine and effective against most C. glabrata isolates. For patients with severe infections, particularly pyelonephritis, an echinocandin (e.g., micafungin or caspofungin) may be used. Although echinocandins do not achieve high concentrations in the urine, they are fungicidal and preferred for systemic candidiasis or when resistance to other agents is a concern.
Addressing Persistent and Recurrent Infections
Persistence of C. glabrata in the urine after initial therapy requires addressing underlying factors. The most important action in managing persistent candiduria is the removal or exchange of any indwelling urinary catheter. Since C. glabrata readily forms biofilms on these foreign bodies, removing the source is necessary for successful eradication.
If the infection persists despite catheter removal and initial treatment, the next step involves switching to a different class of antifungal agent. For example, a patient who failed fluconazole would be transitioned to Amphotericin B deoxycholate or flucytosine, guided by AST results. Elimination of structural abnormalities or obstructions in the urinary tract, such as kidney stones or ureteral stents, is also necessary, as these can serve as fungal reservoirs.
Follow-up urine cultures are essential after therapy to confirm complete eradication, especially in immunocompromised patients. In highly recurrent cases, particularly in patients with kidney transplants or profound immunosuppression, long-term suppressive therapy may be considered. This approach typically involves a prolonged course of an oral antifungal to which the isolate is susceptible.