What is the azole of choice for treating pulmonary mucormycosis?

Posaconazole is the Azole of Choice for Pulmonary Mucormycosis

Posaconazole is the only azole recommended for the treatment of pulmonary mucormycosis, specifically as second-line therapy for patients who are refractory to or intolerant of amphotericin B formulations. 1, 2

First-Line Treatment Considerations

• Amphotericin B lipid formulations remain the first-line therapy for mucormycosis, including pulmonary infections 1, 2
• Posaconazole monotherapy cannot be recommended as primary treatment of mucormycosis (CIII) 1
• Fluconazole and voriconazole have no meaningful activity against Mucorales in vitro and in experimental models 1, 2

Role of Posaconazole in Mucormycosis Treatment

Posaconazole has demonstrated efficacy as second-line therapy for mucormycosis:

• Clinical data from compassionate use programs support posaconazole as an option for patients with mucormycosis who are:

  • Refractory to amphotericin B
  • Intolerant of amphotericin B
  • In need of prolonged continuation or maintenance therapy (BII) 1

• In published case reports, posaconazole has shown a complete response rate of 64.6% when used in combination or as second-line therapy 3

• Therapeutic drug monitoring is strongly recommended when using posaconazole to ensure adequate serum levels 1, 2

Important Clinical Considerations

1. Dosing: Posaconazole has been administered at 200 mg QID or 400 mg BID for extended periods (median 182 days) 1

2. Susceptibility patterns:

   • Posaconazole MICs are lower than those of amphotericin B against Cunninghamella bertholletiae 1
   • Genus and species-specific variations in susceptibility exist 1
   • Strains with posaconazole MIC of 0.25 μg/mL respond better than those with MIC of 2 μg/mL 1

3. Adjunctive measures:

   • Surgical debridement should be considered whenever possible 1, 2
   • Control of underlying conditions (especially diabetes, neutropenia) is crucial 1, 2

Emerging Alternative: Isavuconazole

While posaconazole is currently the azole of choice, isavuconazole shows promise:

• Isavuconazole is a broad-spectrum triazole approved for mucormycosis 4
• In prophylaxis studies, isavuconazole significantly improved survival and lowered tissue fungal burden in mice with pulmonary mucormycosis 5
• However, clinical data for isavuconazole in mucormycosis is still limited compared to posaconazole 1

Pitfalls and Caveats

• Posaconazole has variable bioavailability; therapeutic drug monitoring is essential 1, 2
• MICs of Mucorales for posaconazole (1-4 μg/mL) are higher than those of Aspergillus fumigatus (≤0.5 μg/mL), which may impact efficacy 1
• Combination therapy (posaconazole with amphotericin B) has shown mixed results in animal studies 1
• Treatment failure can occur, particularly with high MIC strains 1

In conclusion, while amphotericin B lipid formulations remain first-line therapy for pulmonary mucormycosis, posaconazole is the only azole currently recommended for treatment, specifically as second-line therapy for patients who cannot tolerate or have failed amphotericin B treatment.