Is there a 2025 guideline for treating candidiasis, especially in patients with underlying medical conditions such as diabetes or immunosuppression?

2025 Candidiasis Treatment Guideline

Yes, there is a comprehensive 2025 global guideline for candidiasis diagnosis and management published in The Lancet Infectious Diseases by the European Confederation for Medical Mycology (ECMM) in cooperation with ISHAM and ASM. 1

Key Updates in the 2025 Guideline

The 2025 guideline represents a significant advancement over previous recommendations, specifically addressing critical gaps in the 2016 IDSA guidelines by incorporating:

• Coverage of emerging pathogens including Candida auris (Candidozyma auris), which was not addressed in prior guidelines and poses a substantial global health threat due to multidrug resistance and healthcare transmission 1

• New antifungal agents including rezafungin, a recently approved echinocandin not available when the 2016 IDSA guidelines were published 1

• Updated diagnostic approaches incorporating biomarkers and molecular diagnostic techniques that have emerged since 2016, though conventional microscopy and culture remain the diagnostic mainstay 1

• Fluconazole-resistant C. parapsilosis as an emerging concern requiring specific management strategies 1

First-Line Treatment Recommendations

Invasive Candidiasis and Candidemia

Echinocandins (including rezafungin) are the recommended first-line treatment for invasive candidiasis, particularly in critically ill patients or those with immunosuppression 1, 2. The standard dosing regimens are:

• Caspofungin: 70 mg loading dose, then 50 mg daily 2
• Micafungin: 100 mg daily 2
• Anidulafungin: 200 mg loading dose, then 100 mg daily 2

Fluconazole (800 mg loading dose, then 400 mg daily) is acceptable only in hemodynamically stable patients without recent azole exposure and unlikely to harbor fluconazole-resistant species 2.

Source Control Measures

• Central venous catheter removal is strongly recommended as early as possible (<48-72 hours) if safely feasible 1
• Daily follow-up blood cultures should continue until three consecutive negative days 1
• If blood cultures remain positive at day 5, repeat search for intravascular or other uncontrolled sources 1

Special Considerations for Underlying Conditions

Diabetes Mellitus

Diabetic patients face increased susceptibility to candidiasis due to disease-related immunosuppression and physiological alterations 3, 4:

• High blood glucose levels promote yeast attachment, growth, and interfere with immune responses 3
• C. albicans is the most common pathogen, though C. glabrata is prominent in type 2 diabetes and less susceptible to conventional antifungals 3
• Establishing and maintaining euglycemia is essential as hyperglycemia increases risk for both incident infection and recurrence 3
• Treatment follows standard guidelines but may require PK/PD optimization due to diabetes-related pharmacokinetic alterations 4

Immunosuppression and Neutropenia

• Echinocandins or liposomal amphotericin B (3-5 mg/kg daily) are strongly preferred in neutropenic patients given the particularly virulent nature of Candida infections in this population 2
• C. tropicalis is especially virulent in neutropenic hosts with frequent hematogenous dissemination 2
• Response rates in neutropenic patients range from 64-69% with appropriate therapy 2
• Neutropenic patients should be treated as recommended for candidemia rather than isolated organ infection 5

Site-Specific Treatment Algorithms

CNS Infections

• Liposomal amphotericin B (LAmB), usually combined with flucytosine, is strongly recommended for CNS candidiasis based on in-vitro susceptibility 1
• Fluconazole (alone or with flucytosine) is strongly recommended as oral consolidation therapy if the species is drug-susceptible 1
• Continue therapy until all signs/symptoms resolve, cerebrospinal fluid normalizes, and imaging evidence clears 1

Ocular Candidiasis

• Fluconazole or voriconazole is recommended for azole-susceptible Candida causing ocular infection 1
• Systemic LAmB is an alternative when resistance to other agents is encountered 1
• Echinocandins should be avoided for endophthalmitis due to poor pharmacokinetics in the posterior chamber 1
• Intravitreal antifungal therapy or vitrectomy should be evaluated case-by-case with ophthalmology 1

Urinary Tract Infections

For pyelonephritis 5:

• Fluconazole-susceptible species: oral fluconazole 200-400 mg (3-6 mg/kg) daily for 2 weeks 5
• Fluconazole-resistant C. glabrata: amphotericin B deoxycholate 0.3-0.6 mg/kg daily for 1-7 days with or without flucytosine 25 mg/kg 4 times daily 5
• Elimination of urinary tract obstruction is strongly recommended 5
• Remove or replace nephrostomy tubes/stents if feasible 5

Asymptomatic candiduria does not require treatment unless the patient is neutropenic, a very low-birth-weight infant, or undergoing urologic manipulation 5.

Mucocutaneous Candidiasis

For oropharyngeal candidiasis 1:

• Mild disease: clotrimazole troches 10 mg 5 times daily OR miconazole mucoadhesive buccal 50-mg tablet once daily for 7-14 days 1
• Moderate to severe: oral fluconazole 100-200 mg daily for 7-14 days 1
• Fluconazole-refractory: itraconazole solution 200 mg once daily OR posaconazole suspension 400 mg twice daily for 3 days then 400 mg daily, for up to 28 days 1

For esophageal candidiasis, fluconazole 100-200 mg daily is first-line, with treatment for minimum 3 weeks and at least 2 weeks after symptom resolution 1.

Treatment Duration and Step-Down Therapy

• Continue therapy for 2 weeks after documented clearance from bloodstream, resolution of symptoms, and resolution of neutropenia 2
• Transition to oral fluconazole (400 mg daily) is reasonable once the patient is clinically stable, blood cultures are negative, and the isolate is confirmed susceptible 2, 6
• Recent evidence supports fluconazole step-down as safe and reasonable for C. glabrata candidemia after initial echinocandin therapy 6

Critical Pitfalls to Avoid

• Do not use echinocandins for endophthalmitis due to poor ocular penetration 1
• Do not treat asymptomatic candiduria in non-high-risk patients 5
• Do not delay central venous catheter removal beyond 48-72 hours when feasible 1
• Do not use fluconazole empirically in critically ill patients or those with recent azole exposure 2
• Do not neglect source control measures, which significantly impact outcomes 2
• In diabetic patients, do not overlook glycemic control as a fundamental component of management 3