Candida glabrata is a species of yeast that has become a significant concern within healthcare settings. It is an opportunistic fungus, meaning it typically lives harmlessly as part of the body’s normal microbial community but can cause severe infection when conditions allow. While often overshadowed by Candida albicans, this organism is gaining increasing medical attention due to its rising prevalence and particular challenges in treatment. Understanding its unique biological traits and resistance profile is crucial for managing the infections it causes in vulnerable patients.
Biological Profile and Natural Habitat
Candida glabrata is a small, single-celled fungus that exists only in the yeast form, unlike other common Candida species that can switch between yeast and filamentous forms. Its cells are noticeably smaller than those of C. albicans, measuring only about one to four micrometers in diameter. A distinguishing characteristic is its haploid genome, unlike the diploid nature of most other pathogenic Candida species.
C. glabrata is a natural resident of the human microbiome, primarily colonizing the gastrointestinal and genitourinary tracts. It coexists with trillions of other microorganisms without causing disease in a healthy host. This yeast is also found in the environment, isolated from sources like soil and plant surfaces.
It is generally considered a commensal organism that maintains a delicate balance with the host’s immune system. However, this balance is easily disrupted by certain medical interventions or underlying health conditions. Once the host’s defenses are weakened, C. glabrata can transition from a benign colonizer to an invasive pathogen.
Infections and Vulnerable Populations
C. glabrata is now the second or third most common cause of candidiasis, the term for any infection caused by Candida yeast. Infections range from superficial mucosal candidiasis, such as oral thrush or vaginal yeast infections, to serious systemic disease. The most concerning presentation is candidemia, a bloodstream infection that can spread to various internal organs.
Invasive candidiasis caused by this species is frequently acquired in hospitals, particularly in intensive care units (ICUs). The fungus can easily adhere to and colonize indwelling medical devices, such as central venous catheters and urinary catheters. These devices provide a direct route for the organism to enter the bloodstream and cause systemic infection.
Specific patient populations face an elevated risk of developing serious C. glabrata infections. These include the elderly and severely immunocompromised individuals, such as those with HIV/AIDS, cancer patients undergoing chemotherapy, and organ transplant recipients on immunosuppressive drugs. Patients who receive broad-spectrum antibiotics for extended periods are also vulnerable, as the antibiotics eliminate competing bacteria, allowing the fungus to overgrow.
Why Treatment Is Difficult
The primary reason C. glabrata is medically significant is its inherent and rapidly acquired resistance to common antifungal medications. Unlike C. albicans, C. glabrata has a naturally reduced susceptibility to azole antifungals, particularly fluconazole, which is often the first-line treatment for other yeast infections. This intrinsic tolerance often renders initial therapy ineffective.
The organism can quickly develop acquired resistance mechanisms, even against drugs it was initially susceptible to. A common mechanism involves the overexpression of specialized proteins known as ATP-binding cassette (ABC) drug efflux pumps (e.g., CgCdr1 and CgSnq2). These pumps actively push antifungal drug molecules out of the yeast cell before they can reach their target, effectively lowering the drug concentration inside the organism.
Mutations in the PDR1 gene, which encodes a transcription factor, often trigger the increased production of these efflux pumps. C. glabrata also develops resistance to echinocandins, a powerful class of antifungals reserved for resistant infections. This resistance is mediated by mutations in the Fks gene, which affects the synthesis of the fungal cell wall.
The formation of a biofilm, a complex layer of microorganisms encased in a matrix on surfaces like catheters, further complicates treatment. Cells within a biofilm are physically protected and exhibit a reduced metabolic state, making them more tolerant to antifungal agents. The cumulative effect of intrinsic resistance, active drug expulsion, and cell wall modification makes C. glabrata a formidable therapeutic challenge.
Identification and Management Strategies
Successful management of C. glabrata infections relies heavily on precise and timely laboratory identification. Initial diagnosis involves culturing the organism from a patient sample, such as blood or urine, on specialized media. Differential media, like Chromagar, helps distinguish C. glabrata from other species, as it produces distinct pink to purple colonies.
Accurate identification often requires molecular techniques to confirm the species and rule out other, less resistant fungi. Due to the high risk of antifungal resistance, Antifungal Susceptibility Testing (AST) is a necessary step after isolation. AST determines which specific antifungal drugs can inhibit the patient’s isolated strain.
Current management protocols often begin with an echinocandin (e.g., caspofungin or micafungin) as the preferred first-line treatment for invasive infections, given the high rate of azole resistance. If the isolate is susceptible, de-escalation to high-dose fluconazole may be considered later. A fundamental component of therapy involves the immediate removal of any infected indwelling medical devices, as the biofilm acts as a persistent source of infection.