Treatment of Aspergillus terreus complex and Rhizopus species infections
Posaconazole is not recommended as primary therapy for Aspergillus terreus complex but is an appropriate second-line treatment option; for Rhizopus species, posaconazole is recommended only as salvage therapy when amphotericin B formulations fail or cannot be tolerated.
Treatment of Aspergillus terreus complex
First-line therapy
- Voriconazole is the recommended first-line treatment for invasive aspergillosis, including A. terreus infections (A-I) 1
- A. terreus is clinically resistant to amphotericin B, making voriconazole particularly important for this species 1
- Isavuconazole is also recommended for treatment of A. terreus due to its activity against species showing high amphotericin B MICs (A-III) 1
Second-line/salvage therapy options
- Posaconazole is recommended as salvage therapy for invasive aspergillosis (B-II), including A. terreus infections that are refractory to voriconazole 1
- In a study of patients with invasive aspergillosis who were refractory to or intolerant of conventional therapy, posaconazole showed a 42% success rate compared to 26% in the control group 2
- Therapeutic drug monitoring is recommended when using posaconazole to ensure adequate serum levels 1
Treatment of Rhizopus species (Mucormycosis)
First-line therapy
- Amphotericin B lipid formulations are the recommended first-line therapy for Rhizopus infections (mucormycosis) 1
- Posaconazole monotherapy cannot be recommended as primary treatment of mucormycosis (CIII) 1
- Fluconazole and voriconazole have no meaningful activity against Rhizopus species in vitro and in experimental models 1
Second-line/salvage therapy options
- Posaconazole is an option for patients with mucormycosis who are refractory to or intolerant of amphotericin B formulations (BII) 1
- In a compassionate use program, posaconazole showed efficacy in treating mucormycosis in patients who failed prior therapy 1
- For Rhizopus oryzae specifically, posaconazole was found to be more potent than itraconazole and amphotericin B in vitro 3
Important considerations for posaconazole use
Formulation and dosing
- Delayed-release tablet and IV solution formulations achieve higher and more reliable serum concentrations than oral suspension 4
- For invasive fungal infections, recommended dosing is 300 mg twice on day 1, followed by 300 mg once daily 5
- Food significantly improves absorption of posaconazole oral suspension 6
Monitoring and safety
- Therapeutic drug monitoring is strongly recommended when using posaconazole for treatment of these infections 1
- Target trough concentrations should be ≥0.5-0.7 μg/mL for efficacy 4
- Posaconazole appears to be better tolerated than voriconazole, with fewer treatment-related adverse events (30% vs 40%) 5
Special considerations
Aspergillus terreus
- Susceptibility testing is recommended before treatment, as there can be strain-specific variations in azole susceptibility 1
- If azole resistance is detected, liposomal amphotericin B therapy is recommended despite general A. terreus resistance to amphotericin B 1
Rhizopus species
- Surgical debridement should be considered in addition to antifungal therapy for mucormycosis whenever possible 1
- Combination therapy of posaconazole with amphotericin B formulations may be considered in refractory cases, as no antagonism has been observed in vitro 3
- Control of underlying conditions (especially diabetes, neutropenia) is crucial for treatment success 1
In summary, while posaconazole has activity against both pathogens, its optimal use differs between them. For A. terreus, it serves as an effective salvage option after voriconazole failure, while for Rhizopus species, it should be reserved for cases where amphotericin B formulations have failed or cannot be tolerated.