Treatment of Aspergillus terreus Infection
For invasive Aspergillus terreus infections, voriconazole is the recommended first-line treatment, NOT amphotericin B, due to intrinsic amphotericin B resistance in most A. terreus isolates. 1, 2
Primary Treatment Approach
Voriconazole should be initiated as first-line therapy for invasive A. terreus infections, following the standard dosing for invasive pulmonary aspergillosis: 6 mg/kg IV every 12 hours for 1 day, followed by 4 mg/kg IV every 12 hours, with transition to oral therapy at 200-300 mg every 12 hours when appropriate 1. This recommendation is based on the IDSA 2016 guidelines for invasive aspergillosis, which designate voriconazole as primary therapy with strong evidence 1.
Critical Species-Specific Consideration
The A. terreus species complex demonstrates intrinsic resistance to amphotericin B in most isolates 3, 4. Clinical data demonstrate that patients with A. terreus infections treated with amphotericin B have significantly worse outcomes, with mortality rates of 73.4% compared to 55.8% with voriconazole 4. This poor prognosis persists even when isolates appear susceptible by MIC testing, likely due to drug tolerance mechanisms 5.
Alternative Treatment Options
If voriconazole cannot be used due to contraindications, drug interactions, or resistance:
- Isavuconazole (200 mg every 8 hours for 6 doses, then 200 mg daily) is an appropriate alternative azole 1, 2
- Posaconazole can serve as third-line azole therapy (oral suspension: 200 mg TID; tablet: 300 mg BID day 1, then 300 mg daily) 1
- Liposomal amphotericin B (3-5 mg/kg/day IV) should be reserved for azole-resistant isolates or when azoles are contraindicated 1, 2, 6
- Echinocandins (caspofungin or micafungin) may be considered when both azoles and polyenes are contraindicated, though they are not recommended as primary monotherapy 1, 7
Essential Management Components
Antifungal Susceptibility Testing
Perform antifungal susceptibility testing on all A. terreus isolates to guide therapy, particularly for azole susceptibility 1, 2, 6. This is critical because:
- Azole resistance can occur in A. terreus
- Amphotericin B MICs may be misleading due to tolerance mechanisms 5
- Individual isolates may show variable susceptibility patterns 6
Therapeutic Drug Monitoring
Obtain serum trough levels for voriconazole once steady state is reached (strong recommendation) 1. Target trough concentrations of 1-5.5 μg/mL optimize efficacy while minimizing toxicity. This is particularly important given:
- High inter-patient variability in voriconazole pharmacokinetics
- Potential drug interactions with immunosuppressants (cyclosporine, tacrolimus, sirolimus)
- Need for adequate drug exposure in severe infections
Duration of Therapy
Continue treatment for a minimum of 6-12 weeks, with duration dependent on 1:
- Degree and duration of immunosuppression
- Site and extent of disease
- Clinical and radiographic response
Adjunctive Measures
Reduce or eliminate immunosuppressive agents when feasible as a critical component of therapy (strong recommendation) 1. Consider:
- Surgical debridement for localized, accessible disease 1, 8
- Colony-stimulating factors in neutropenic patients 1
- Secondary prophylaxis if subsequent immunosuppression is required 1
Common Pitfalls to Avoid
Do not use amphotericin B as first-line therapy for A. terreus, even if in vitro testing suggests susceptibility—clinical outcomes are consistently poor 9, 4, 5
Do not assume all Aspergillus species respond similarly to treatment—A. terreus has distinct resistance patterns requiring species-specific management 3, 9
Do not rely solely on MIC values for amphotericin B—tolerance mechanisms may result in treatment failure despite apparently susceptible MICs 5
Do not delay antifungal susceptibility testing—early identification of A. terreus and its susceptibility profile is essential for optimal outcomes 6