Which azoles are ineffective in treating Mucor infections, specifically mucormycosis?

Ineffective Azoles Against Mucor

Fluconazole and voriconazole lack meaningful in vitro activity against Mucorales and should never be used for treatment of mucormycosis. 1

Azoles Without Activity

The following azoles are ineffective against Mucor and other Mucorales:

Completely Ineffective Azoles

• Fluconazole has no meaningful in vitro activity against any Mucorales species and should be avoided entirely 1
• Voriconazole lacks meaningful activity against Mucorales in both in vitro and experimental animal models 1

Critical Clinical Caveat

There is concerning evidence that voriconazole prophylaxis or empirical therapy may paradoxically allow for longer patient survival, thereby increasing exposure time and risk for developing mucormycosis as a breakthrough infection. 1 This represents a dangerous clinical scenario where voriconazole successfully treats susceptible fungi (like Aspergillus) but leaves patients vulnerable to Mucorales.

Azoles With Limited or Variable Activity

Itraconazole

• Despite not being recommended for mucormycosis treatment, itraconazole demonstrates relatively low MICs for certain strains, particularly Rhizomucor and Lichtheimia species 1
• However, it is not recommended for clinical use in mucormycosis treatment 1

Isavuconazole

• Shows variable activity with MIC50 values of 1-4 mg/mL and MIC90 values of 4-16 mg/mL against Mucorales 1
• In vitro studies show MIC90 values over 8 mg/mL against 36 strains, which is significantly higher than posaconazole (MIC90 of 1-4 mg/mL) 1
• Clinical trial data (VITAL study) showed 33% day-42 mortality, similar to amphotericin B-treated controls 2
• Recent evidence suggests isavuconazole has species-dependent activity and may be considered as an alternative or salvage option 3, 2, 4

The Only Effective Azole

Posaconazole is the only azole with meaningful activity against Mucorales and is recommended as:

• Salvage therapy for patients refractory to or intolerant of amphotericin B 1, 5
• Prolonged continuation or maintenance therapy 1
• NOT as primary monotherapy 1

Posaconazole demonstrates the most consistent in vitro activity among azoles, with amphotericin B remaining the most active drug overall 1

Important Species-Specific Variations

The susceptibility of Mucorales to azoles varies significantly by genus and species:

• Amphotericin B yields lower MICs than posaconazole against Mucor circinelloides 1
• Posaconazole MICs are lower than amphotericin B against Cunninghamella bertholletiae 1
• Both agents show high MICs against Cunninghamella echinulata 1
• Significant strain-based variations exist, particularly for Rhizopus and Mucor species 1, 3