What is the treatment for Candida (fungal infection) urine infection in a patient with deranged Liver Function Tests (LFTs)?

From the Guidelines

The treatment for Candida urinary tract infection in a patient with deranged liver function tests typically involves fluconazole, but requires dose adjustment based on liver impairment severity, as recommended by the Infectious Diseases Society of America 1. For mild to moderate liver dysfunction, fluconazole 100-200 mg daily for 7-14 days is recommended, with the lower dose preferred initially.

• The choice of antifungal depends on Candida species identification, as some species like C. glabrata and C. krusei have reduced fluconazole susceptibility 1.
• In severe liver impairment, the dose should be reduced by 50% or alternative agents considered, such as echinocandins like caspofungin or micafungin, which may be used for fluconazole-resistant species or in patients with severe hepatic dysfunction, though these require intravenous administration 1.
• Amphotericin B deoxycholate is another option but carries nephrotoxicity risks, and its use is generally discouraged, especially in patients who would not require an indwelling catheter for any other reason 1. Before starting treatment, it's essential to distinguish between colonization and true infection, as asymptomatic candiduria often doesn't require treatment, as noted in the clinical practice guidelines for the management of candidiasis: 2016 update by the Infectious Diseases Society of America 1.
• Removal of indwelling catheters should be attempted when possible, and liver function should be monitored during treatment, with tests performed at baseline and periodically throughout therapy 1. The most recent and highest quality study, published in 2016, provides the best guidance for the treatment of Candida urinary tract infection in patients with deranged liver function tests, and its recommendations should be followed to minimize morbidity, mortality, and improve quality of life 1.

From the FDA Drug Label

The overall clinical and mycological success rates by Candida species in Study 150-608 are presented in Table 15. Table 15: Overall Success Rates Sustained From EOT To The Fixed 12-Week Follow-Up Time Point By Baseline Pathogen C. albicans 46/107 (43%) 30/63 (48%) C. tropicalis 17/53 (32%) 1/16 (6%) C. parapsilosis 24/45 (53%) 10/19 (53%) C. glabrata 12/36 (33%) 7/21 (33%) C krusei 1/4 0/1

Treatment for Candida Urine Infection in Deranged LFTs:

• The provided drug label does not directly address the treatment of Candida urine infection in patients with deranged Liver Function Tests (LFTs).
• However, it does provide information on the treatment of candidemia and deep tissue Candida infections using voriconazole.
• In patients with deep tissue Candida infections, including kidney and bladder wall infections, a favorable response was seen in 5 of 6 patients treated with voriconazole 2.
• However, the label does not provide specific guidance on dosing or treatment in patients with deranged LFTs.
• Therefore, caution should be exercised when using voriconazole in patients with liver dysfunction, and alternative treatments may be considered.

From the Research

Treatment Options for Candida Urine Infection

• The treatment of symptomatic candiduria is challenging due to the limited repository of antifungals that achieve adequate urinary concentrations 3, 4.
• Established treatment options for most Candida species include fluconazole, amphotericin B-based products, and flucytosine 3, 4.
• However, Candida krusei exhibits intrinsic resistance to fluconazole and decreased susceptibility to amphotericin B and flucytosine 3.
• In patients with deranged Liver Function Tests (LFTs), the use of antifungal agents such as fluconazole may worsen liver function 5, 6.

Considerations for Patients with Deranged LFTs

• Liver function should be monitored during the course of antifungal therapy in patients with underlying liver dysfunction 5, 6.
• The development of LFT abnormalities while on antifungal therapy may not warrant a switch to an alternative antifungal, as hepatotoxicity is often multifactorial and generally resolves with time in the majority of patients 7.
• Echinocandins, such as micafungin, may be a viable treatment option for symptomatic candiduria in patients with deranged LFTs, despite their poor urinary concentrations 3.

Antifungal Agents and Hepatotoxicity

• All antifungal agents, including amphotericin B formulations, echinocandins, and triazoles, may cause hepatic toxicity that ranges from mild and asymptomatic abnormalities in liver function tests to substantial liver injury and fulminant hepatic failure 6.
• A thorough understanding of the distribution, metabolism, elimination, and drug-drug interactions of antifungal agents used for management of invasive fungal diseases (IFDs) in combination with safety data from clinical trials, pharmacokinetic, and pharmacodynamic studies may guide the use of antifungal treatment in patients at high risk for the development of hepatic dysfunction and in those with underlying liver damage due to cytotoxic therapy 6.