Candida glabrata is a species of yeast that is a common cause of fungal infections, particularly in hospitalized patients and those with weakened immune systems. While it belongs to the same genus as Candida albicans, the yeast responsible for most typical infections, C. glabrata is known as a non-albicans species that presents a greater challenge to treat. This is because it possesses an ability to withstand certain standard antifungal medications, making the therapeutic approach specialized. Successfully managing this infection requires precise laboratory identification, an understanding of its resistance profile, and the selection of appropriate, high-potency antifungal agents. Medical oversight from an infectious disease specialist is often necessary.
Identifying the Infection
A definitive diagnosis of a C. glabrata infection depends entirely on laboratory confirmation, as the symptoms of candidiasis are not unique to the species. The initial step involves culturing a sample from the infection site, such as blood, urine, or an indwelling catheter tip, to isolate the causative organism. Once a Candida species is isolated, specialized molecular or biochemical testing is performed to specifically identify it as C. glabrata, distinguishing it from other species. This identification is a time-sensitive process, as treatment decisions hinge on knowing the exact pathogen involved.
Upon identification, the isolate must undergo Antifungal Sensitivity Testing (AST), also referred to as susceptibility testing. This laboratory procedure determines precisely which antifungal medications are effective against that specific strain of C. glabrata. The results of AST are paramount, guiding the treating physician away from drugs that may fail and toward those with proven efficacy. While traditional culture and AST results can take 48 to 72 hours, newer rapid diagnostic methods are increasingly used to accelerate the reporting time and allow for faster initiation of targeted therapy.
Understanding Antifungal Resistance
Treating C. glabrata is difficult because the organism exhibits an intrinsic reduced susceptibility to a common class of antifungals called azoles, especially Fluconazole. This resistance is often present from the start, unlike C. albicans, which typically develops resistance only after prolonged drug exposure. This reduced sensitivity means that Fluconazole, the historical first-line treatment for many yeast infections, is often unreliable as initial therapy for a serious C. glabrata infection.
The primary mechanism driving this resistance involves the overexpression of specific drug efflux pump genes, such as CgCDR1 and PDH1. These genes produce proteins that actively pump the Fluconazole drug out of the fungal cell before it can reach its target. This active efflux mechanism prevents the antifungal agent from accumulating to the necessary concentrations required to effectively kill the yeast. Because of this, even when a strain is not fully resistant, it often requires substantially higher drug concentrations to achieve a therapeutic effect.
First-Line Treatment Strategies
For systemic or serious localized infections caused by C. glabrata, the first-line treatment strategy focuses on a class of drugs called Echinocandins. These medications, which include Caspofungin, Micafungin, and Anidulafungin, work by inhibiting the synthesis of beta-(1,3)-D-glucan, a component of the fungal cell wall. By disrupting this structural element, Echinocandins effectively compromise the integrity of the yeast cell, leading to its death.
Echinocandins are preferred as initial therapy because they retain strong activity against most strains of C. glabrata, including those that are resistant to Fluconazole. For serious infections like candidemia, the medication is typically administered intravenously (IV) to ensure rapid and high drug concentrations reach the site of infection. Treatment regimens usually begin with a loading dose to quickly achieve therapeutic levels, followed by a daily maintenance dose.
The duration of this initial, aggressive therapy is typically extended, often continuing for a minimum of two weeks after the patient shows clinical improvement and follow-up blood cultures are negative. A primary component of first-line management for bloodstream infections is source control, which involves the prompt removal of any infected indwelling medical device, such as a central venous catheter. This combined approach of high-potency IV antifungal therapy and source removal maximizes the chances of clearing the infection.
Managing Persistent or Refractory Cases
If the initial Echinocandin therapy fails, or if the infecting strain is found to be resistant to Echinocandins, the case is considered refractory and requires alternative or salvage treatment options. A lipid formulation of Amphotericin B is often brought into the treatment plan. Amphotericin B is a broad-spectrum antifungal that works by binding to ergosterol, a component of the fungal cell membrane, creating pores that cause the cell to leak and die.
Lipid formulations of Amphotericin B are favored over the older deoxycholate form because they retain the drug’s effectiveness while significantly reducing the risk of severe side effects, such as kidney damage. Another agent frequently used in combination therapy is Flucytosine, an oral drug that interferes with the yeast’s DNA and RNA synthesis. Flucytosine is rarely used alone due to the rapid development of resistance, but it is highly effective when combined with Amphotericin B, particularly for infections in the urinary tract or central nervous system.
Once the infection is clinically controlled and the patient is stable, a transition to an oral regimen, known as step-down therapy, may be considered for continued management. This step-down may involve high-dose Fluconazole, typically 800 mg daily, but only if the original AST confirmed the C. glabrata isolate is still susceptible to the drug. If the isolate is Fluconazole-resistant, other oral azoles like Voriconazole or Posaconazole may be considered, provided susceptibility data supports their use. Continuous monitoring and repeated susceptibility testing are performed throughout this phase to ensure the treatment remains effective and to detect any emerging drug resistance.