What is a suitable intravenous (IV) antifungal agent for a patient with a positive urine culture for Candida glabrata?

Treatment of Candida glabrata Urinary Tract Infection

For a patient with a positive urine culture for Candida glabrata, the first critical step is determining whether this represents true infection versus colonization—if symptomatic, fluconazole 200-400 mg IV daily for 2 weeks is the preferred IV antifungal, though echinocandins (micafungin 100 mg IV daily, caspofungin 50 mg IV daily, or anidulafungin 100 mg IV daily) should be strongly considered for fluconazole-resistant isolates or critically ill patients. 1

Initial Assessment: Infection vs. Colonization

• Asymptomatic candiduria does not require treatment in most patients, as it typically represents colonization rather than true infection 2, 3, 4
• Treatment is indicated only for: symptomatic cystitis/pyelonephritis, neutropenic patients, very low-birth-weight neonates, or patients undergoing urologic procedures 1, 2, 5
• Removing or replacing urinary catheters resolves candiduria in approximately 40-50% of cases without antifungal therapy, making this the first intervention 2, 3, 6

IV Antifungal Selection for Symptomatic C. glabrata UTI

First-Line: Fluconazole (with important caveats)

• Fluconazole 200-400 mg (3-6 mg/kg) IV daily for 2 weeks is the standard treatment for symptomatic C. glabrata cystitis, achieving urinary concentrations 10-20 times serum levels 1, 2, 5
• Critical caveat: C. glabrata has reduced susceptibility to fluconazole compared to C. albicans, and resistance is increasingly common 1, 6
• Higher doses (400 mg daily or 12 mg/kg) are often recommended for C. glabrata, though this has not been validated in clinical trials 1
• Do not use fluconazole if the patient has recent azole exposure or if susceptibility testing shows resistance 1

Alternative: Amphotericin B Deoxycholate

• Amphotericin B deoxycholate 0.3-0.6 mg/kg IV daily for 1-7 days is effective for fluconazole-resistant C. glabrata UTI 1, 3
• This achieves adequate urinary concentrations and is particularly useful for resistant isolates 4, 7
• Avoid lipid formulations of amphotericin B (liposomal, lipid complex) for UTI as they do not achieve adequate urine concentrations due to reduced renal excretion 1, 3, 5

Echinocandins: Limited Role but Important Exceptions

• Echinocandins (micafungin 100 mg IV daily, caspofungin 50 mg IV daily, anidulafungin 100 mg IV daily) do not achieve adequate urinary concentrations and are generally NOT recommended for isolated UTI 3, 5, 6
• However, echinocandins are the preferred agents if there is concern for disseminated candidiasis or candidemia with concurrent urinary involvement 1, 8
• Small case series report successful treatment of C. glabrata UTI with micafungin, but failures have also occurred 9, 4

Special Clinical Scenarios

For Pyelonephritis or Upper Tract Infection

• Fluconazole 200-400 mg (3-6 mg/kg) IV daily for 2 weeks, using the higher dose range (400 mg) for more severe infections 2, 5
• If fluconazole-resistant: Amphotericin B deoxycholate 0.3-0.6 mg/kg IV daily with or without flucytosine 25 mg/kg orally four times daily 1, 3, 5

For Fungal Bezoars or Obstruction

• Surgical intervention or percutaneous drainage is essential in addition to antifungal therapy 2, 7
• Multi-route administration may be necessary: systemic IV amphotericin B combined with local instillation through nephrostomy tube 7
• Imaging of the genitourinary tract is indicated if treatment fails or if fungus balls are suspected 2, 5

For Critically Ill or Neutropenic Patients

• Echinocandins are preferred if there is concern for disseminated infection beyond isolated UTI 1
• Consider that candiduria may represent hematogenous seeding from candidemia rather than ascending infection 3, 4
• Assess for disseminated candidiasis with ophthalmologic examination and imaging 1

Critical Management Steps Beyond Antifungals

• Remove or replace all urinary catheters if feasible—this is as important as antifungal therapy 2, 3, 6
• Eliminate urinary tract obstruction urgently as obstruction precludes successful antifungal treatment 3, 5
• Discontinue unnecessary antibiotics that may be predisposing to candiduria 6, 4

Common Pitfalls to Avoid

• Do not use voriconazole, posaconazole, or itraconazole for UTI—these azoles do not achieve adequate urinary concentrations 1, 6, 4
• Do not use echinocandins as monotherapy for isolated UTI unless there is evidence of disseminated infection 3, 5, 6
• Do not use lipid formulations of amphotericin B for UTI due to inadequate urinary excretion 1, 3, 5
• Do not treat asymptomatic candiduria unless the patient is neutropenic, a neonate, or undergoing urologic procedures 2, 3, 4

Monitoring and Duration

• Standard duration is 2 weeks for symptomatic cystitis or pyelonephritis 2, 3, 5
• Continue therapy until symptoms resolve and urine cultures no longer yield Candida species 2, 5
• Obtain follow-up urine cultures to confirm clearance 3, 5
• If treatment fails despite appropriate therapy, obtain imaging to rule out anatomical abnormalities, fungus balls, or abscesses 2, 5

Transition to Oral Therapy

• Once clinically stable and susceptibility confirmed, transition from IV fluconazole to oral fluconazole at the same dose (oral bioavailability ~90%) 1, 10
• For patients initially treated with echinocandins for candidemia with concurrent UTI, fluconazole step-down is safe and reasonable once blood cultures clear and susceptibility is confirmed 10