Efficacy and Safety of Current Drug Therapies for Invasive Aspergillosis

Invasive aspergillosis (IA) is a potentially lethal infection that affects mostly immunocompromised patients. The therapeutic goals are to restore leucocyte function and to reduce the fungal burden by effective antifungal agents and, contingently, by surgery. Several drugs for the treatment of IA are currently licensed. The longest known among them is amphotericin B (AmB). In well-performed clinical trials, approximately 30–50% of participants treated with AmB showed complete or partial response. However, this drug is associated with considerable acute and chronic toxicity which was somewhat mitigated by the development of lipid-based formulations. In contrast, voriconazole (VRC) is better tolerated, penetrates well into the central nervous system and may be given intravenously and orally in a sequential manner. The overall rates of favourable response to VRC were similar to that for AmB. Most notably, double-digit rates of complete remission were observed in studies including extraordinarily high proportions of patients with proven IA and specific risk factors. Disadvantages of VRC include the genetically determined interindividual variability of pharmacokinetics and the potential for drug-drug interactions that may require therapeutic drug monitoring. The recently introduced caspofungin (CPF) offers an excellent safety profile, but underperformed in terms of efficacy against mold infections. Other antifungals such as itraconazole and posaconazole are presently recommended as second-line option for the therapy or prophylaxis of (non-)IA. The value of micafungin and anidulafungin remains to be investigated in randomized clinical trials. In guidelines released by relevant medical societies, VRC is recommended as the first choice in the treatment of IA. AmB, preferably given as a liposomal preparation, or combinatory antifungal regimens combining VRC or liposomal AmB with CPF are stated as alternative options.