What are alternative systemic therapies for candida (fungal infection) besides fluconazole (Diflucan)?

Alternative Systemic Therapies for Candida Infections

Echinocandins (caspofungin, micafungin, or anidulafungin) are the preferred alternative systemic therapies for invasive candidiasis, particularly in critically ill patients, those with recent azole exposure, or suspected azole-resistant species. 1

Primary Alternative Agents by Clinical Scenario

Echinocandins (First-Line Alternatives)

For invasive candidiasis and candidemia in non-neutropenic adults:

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

Echinocandins are specifically preferred over fluconazole when: 1

• The patient is critically ill or hemodynamically unstable
• Recent azole exposure has occurred
• Infection with C. glabrata or C. krusei is suspected or confirmed
• The patient has moderate to severe illness

Amphotericin B Formulations

Amphotericin B deoxycholate: 0.5-1.0 mg/kg daily IV is an effective alternative when echinocandins or azoles cannot be used due to intolerance or limited availability 1

Liposomal amphotericin B (L-AmB): 3-5 mg/kg daily is preferred over deoxycholate formulation due to reduced toxicity, though it carries higher cost 1

For CNS candidiasis specifically, amphotericin B deoxycholate 1 mg/kg daily IV is the recommended initial treatment, with liposomal amphotericin B 5 mg/kg daily as an alternative 1

Other Azole Alternatives

Voriconazole: 400 mg (6 mg/kg) IV every 12 hours for two loading doses, then 200 mg (3 mg/kg) twice daily 1

• Effective for candidemia but offers little advantage over fluconazole for susceptible species 1
• Recommended specifically for C. krusei infections 1
• Consider for step-down oral therapy in voriconazole-susceptible C. glabrata 1

Itraconazole solution: 200 mg daily is effective for esophageal candidiasis, achieving 64-80% efficacy in fluconazole-refractory cases 1, 2

Posaconazole: 400 mg twice daily (suspension) or 300 mg once daily (extended-release tablets) demonstrates approximately 75% efficacy in fluconazole-refractory disease 1, 2

Species-Specific Considerations

Candida glabrata

An echinocandin is strongly preferred as first-line therapy due to reduced azole susceptibility 1

• Liposomal amphotericin B is an effective but less attractive alternative 1
• If already receiving an azole with clinical improvement and negative follow-up cultures, continuing the azole to completion is reasonable 1

Candida parapsilosis

Fluconazole or liposomal amphotericin B is preferred over echinocandins due to higher MICs observed with echinocandins against this species 1, 3

• If receiving an echinocandin with clinical stability and negative cultures, continuing to completion is acceptable 1

Candida krusei

This species is intrinsically resistant to fluconazole 4, 5

• Recommended alternatives: echinocandin, liposomal amphotericin B, or voriconazole 1

Special Populations

Neonates with Disseminated Candidiasis

Amphotericin B deoxycholate 1 mg/kg daily is the primary recommendation 1

• Fluconazole 12 mg/kg IV or oral daily is reasonable if not on fluconazole prophylaxis 1
• Liposomal amphotericin B 3-5 mg/kg daily is an alternative but use with caution in urinary tract involvement 1
• Echinocandins should be used with extreme caution and limited to salvage therapy or when resistance/toxicity precludes amphotericin B or fluconazole 1

Esophageal Candidiasis

For patients unable to tolerate oral therapy: 1

• Echinocandin (micafungin 150 mg daily, caspofungin 70 mg loading then 50 mg daily, or anidulafungin 200 mg daily) 1
• Amphotericin B deoxycholate 0.3-0.7 mg/kg daily (less preferred) 1

For fluconazole-refractory esophageal disease: 1, 2

• Itraconazole solution 200 mg daily
• Voriconazole 200 mg (3 mg/kg) twice daily
• Posaconazole suspension 400 mg twice daily
• Echinocandin or amphotericin B formulations

Empiric Therapy in ICU Patients

For critically ill patients with risk factors and no other fever source: 1

• Echinocandin is preferred (same dosing as above)
• Fluconazole 800 mg loading, then 400 mg daily can be used in ICUs with high (>5%) invasive candidiasis rates 1

Combination Therapy

Flucytosine 25 mg/kg four times daily may be added to amphotericin B for CNS candidiasis as salvage therapy in patients not responding to initial amphotericin B, though adverse effects are frequent 1

• Flucytosine is rarely administered as monotherapy 1
• Requires dose adjustment in renal dysfunction 1

Key Clinical Pitfalls to Avoid

Do not use fluconazole for empiric therapy in patients who have received azole prophylaxis - resistance is likely and treatment failure expected 1

Do not assume all echinocandins are equivalent for C. parapsilosis - this species has higher MICs to echinocandins, making fluconazole or amphotericin B preferred 1, 3

Do not use lipid formulation amphotericin B with caution in urinary tract candidiasis - it achieves poor urinary concentrations 1

Do not delay catheter removal - central venous catheter removal is strongly recommended in candidemia and significantly impacts outcomes 1

Do not use itraconazole capsules for mucosal candidiasis - only the oral solution formulation is effective due to superior bioavailability 2