How does the management of candidiasis differ according to the 2025 global guideline, particularly in immunocompetent and immunocompromised patients?

Management Differences in the 2025 Global Candidiasis Guidelines

The most significant evolution in candidiasis management is the shift from amphotericin B to echinocandins as first-line therapy for invasive disease, with distinct treatment algorithms now clearly delineated based on immune status, infection site, and Candida species susceptibility patterns. 1, 2

Key Changes in Invasive Candidiasis Management

First-Line Therapy Evolution

Echinocandins are now the definitive first-line agents for candidemia and invasive candidiasis, replacing the historical reliance on amphotericin B that dominated through the 1980s-2000s 1, 3. The recommended regimens are:

• Caspofungin: 70 mg loading dose, then 50 mg daily 1, 2
• Micafungin: 100 mg daily 1, 2
• Anidulafungin: 200 mg loading dose, then 100 mg daily 1, 2

Fluconazole (800 mg loading dose, then 400 mg daily) remains acceptable only for non-critically ill patients unlikely to harbor fluconazole-resistant species, representing a major departure from earlier guidelines where azoles were more broadly recommended 1, 2.

Treatment Duration and De-escalation Strategy

Treatment must continue for 14 days after documented clearance of Candida from bloodstream AND resolution of symptoms, not simply 14 days from initiation 2. This represents a more rigorous endpoint than earlier recommendations 1.

Step-down from echinocandin to fluconazole is recommended within 5-7 days for clinically stable patients with susceptible isolates and negative repeat blood cultures 2, allowing for cost-effective completion of therapy while maintaining efficacy.

Immunocompromised vs. Immunocompetent Distinctions

Oropharyngeal and Esophageal Candidiasis

For immunocompromised patients with oropharyngeal disease:

• Mild disease: Clotrimazole troches 10 mg five times daily OR miconazole mucoadhesive buccal 50 mg once daily for 7-14 days 1, 2
• Moderate-severe disease: Oral fluconazole 100-200 mg daily for 7-14 days 1, 2

For esophageal candidiasis, systemic therapy is mandatory (topical agents are ineffective) 1:

• First-line: Oral fluconazole 200-400 mg daily for 14-21 days 1
• For patients unable to tolerate oral therapy: IV fluconazole 400 mg daily OR echinocandin (micafungin 150 mg daily, caspofungin 70 mg loading then 50 mg daily, or anidulafungin 200 mg daily) 1

Critical distinction: Echinocandins require higher doses for esophageal disease (e.g., micafungin 150 mg vs. 100 mg for candidemia) due to higher relapse rates observed with standard dosing 1.

Fluconazole-Refractory Disease Management

For azole-refractory mucosal candidiasis (primarily in advanced AIDS patients with CD4 <50 cells/mm³):

• Itraconazole solution 200 mg daily (responds in ~67-80% of cases) 1
• Voriconazole 200 mg twice daily (IV or oral) for 14-21 days 1
• Echinocandins at higher doses (as above) 1
• Posaconazole suspension 400 mg twice daily OR extended-release tablets 300 mg once daily (weaker recommendation) 1

Chronic suppressive therapy with fluconazole 100-200 mg three times weekly is recommended for recurrent esophagitis, though this increases development of isolates with elevated fluconazole MICs 1. The critical caveat: antiretroviral therapy in HIV-infected patients dramatically reduces recurrence rates and is strongly recommended 1.

Urinary Tract Candidiasis

Asymptomatic Candiduria

Treatment is NOT recommended for asymptomatic candiduria except in three specific populations 2, 4:

• Neutropenic patients 2, 4
• Very low-birth-weight infants (<1500 g) 2, 4
• Patients undergoing urologic manipulation 2, 4

Catheter removal is strongly recommended when feasible, as this alone often eliminates candiduria without antifungal therapy 1, 2, 4.

Candida Cystitis and Pyelonephritis

For fluconazole-susceptible species:

• Cystitis: Oral fluconazole 200 mg daily for 2 weeks 1, 2, 4
• Pyelonephritis: Oral fluconazole 200-400 mg daily for 2 weeks 1, 2, 4

For 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 four times daily 1, 2, 4

Critical adjunctive measures that determine treatment success:

• Elimination of urinary tract obstruction is mandatory 4
• Removal or replacement of nephrostomy tubes/stents when feasible 4

Important distinction: Amphotericin B bladder irrigation is generally discouraged (>90% initial response but high relapse rate) except for refractory cystitis due to azole-resistant organisms 1. Lipid formulations of amphotericin B should NOT be used for renal infections due to poor tissue penetration 1.

Neonatal Candidiasis

Amphotericin B deoxycholate 1 mg/kg daily remains first-line therapy for neonates with disseminated candidiasis, representing a major difference from adult management where echinocandins dominate 2. Fluconazole 12 mg/kg daily is a reasonable alternative only in patients not receiving fluconazole prophylaxis 2.

Diagnostic and Susceptibility Testing Requirements

Azole susceptibility testing is now mandatory for all bloodstream and clinically relevant Candida isolates 1, 2, reflecting the increasing prevalence of non-albicans species and azole resistance 1, 5.

Echinocandin susceptibility testing should be considered for:

• Patients with prior echinocandin exposure 1, 2
• Infections with C. glabrata or C. parapsilosis 1, 2

This represents a significant shift from earlier guidelines where susceptibility testing was recommended primarily for treatment failures 1.

Source Control Measures

Central venous catheter removal is strongly recommended for non-neutropenic patients when the catheter is the presumed source 2, a more definitive stance than earlier recommendations 1.

Dilated fundoscopic examination is recommended within the first week for all non-neutropenic patients with candidemia 2, as endophthalmitis can lead to irreversible vision loss if treatment is delayed 1.

Common Pitfalls to Avoid

Do not use lipid formulations of amphotericin B for urinary tract infections due to inadequate urinary and renal tissue concentrations 1. Documented treatment failures have occurred in both animal models and patients 1.

Do not assume all Candida species have similar susceptibility patterns: C. glabrata and C. krusei demonstrate intrinsic or dose-dependent resistance to fluconazole, while C. parapsilosis shows reduced echinocandin susceptibility 1, 5.

Do not continue empiric broad-spectrum therapy without source control: failure to remove infected catheters or relieve urinary obstruction leads to treatment failure regardless of antifungal choice 1, 2, 4.

Avoid prolonged prophylaxis or suppressive therapy without clear indication, as this drives emergence of azole-resistant species, particularly C. glabrata and C. krusei 1, 3. However, when suppressive therapy is indicated (e.g., recurrent esophagitis in AIDS), the clinical benefit outweighs resistance concerns 1.