Treatment of Aspergillosisa
| Indication | Primary Treatment | Evidence Levelb | Precautions | Secondary Treatment | Comments |
|---|---|---|---|---|---|
| Invasivec | Voriconazole | AI | Drug interactions (especially with rifampin), renal failure (IV only) | AmB, caspofungin, posaconazole, micafungin | As primary therapy, voriconazole carries 20% more responses than AmB. Consider initial combination therapy with an echinocandin in non-neutropenic pts. |
| Prophylaxis | Posaconazole, itraconazole solution | AI | Diarrhea and vomiting with itraconazole, vincristine interaction | Micafungin, aerosolized AmB | Some centers monitor plasma levels of itraconazole and posaconazole. |
| Single aspergilloma | Surgery | BII | Multicavity disease: poor outcome of surgery, medical therapy preferable | Itraconazole, voriconazole, intracavity AmB | Single large cavities with an aspergilloma are best resected. |
| Chronic pulmonaryc | Itraconazole, voriconazole | BII | Poor absorption of itraconazole capsules with proton pump inhibitors or H2 blockers | Posaconazole, IV AmB, IV micafungin | Resistance may emerge during treatment, especially if plasma drug levels are subtherapeutic. |
| ABPA/SAFS | Itraconazole | AI | Some glucocorticoid interactions, including with inhaled formulations | Voriconazole, posaconazole | Long-term therapy is helpful in most cases. No evidence indicates whether therapy modifies progression to bronchiectasis/fibrosis. |
aFor information on duration of therapy, see text.
bEvidence levels are those used in treatment guidelines (TJ Walsh et al: Treatment of aspergillosis: Clinical practice guidelines of the Infectious Diseases Society of America [IDSA]. Clin Infect Dis 46:327, 2008).
cAn infectious disease consultation is appropriate for these pts.
Note: The oral dose is usually 200 mg bid for voriconazole and itraconazole and 400 mg bid for posaconazole suspension. The IV dose of voriconazole for adults is 6 mg/kg twice at 12-h intervals (loading doses) followed by 4 mg/kg q12h; a larger dose is required for children and teenagers. Plasma monitoring is helpful in optimizing the dosage. Caspofungin is given as a single loading dose of 70 mg and then at 50 mg/d; some authorities use 70 mg/d for pts weighing >80 kg, and lower doses are required with hepatic dysfunction. Micafungin is given as 50 mg/d for prophylaxis and as at least 150 mg/d for treatment; this drug has not yet been approved by the FDA for this indication. AmB deoxycholate is given at a daily dose of 1 mg/kg if tolerated. Several strategies are available for minimizing renal dysfunction. Lipid-associated AmB is given at 3 mg/kg (AmBisome) or 5 mg/kg (Abelcet). Different regimens are available for aerosolized AmB, but none is FDA approved. Other considerations that may alter dose selection or route include age; concomitant medications; renal, hepatic, or intestinal dysfunction; and drug tolerability.
Abbreviations: ABPA, allergic bronchopulmonary aspergillosis; AmB, amphotericin B; SAFS, severe asthma with fungal sensitization.