Guideline based treatment of invasive aspergillosis

Invasive fungus infections caused by aspergillus spp. occur most frequently in immunocompromised patients. A high infection-associated death rate of up to and over 50% is attributed even today to these fungi. The disease in humans is caused mainly by Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. Other species, for example, Aspergillus terreus or Aspergillus nidulans are quantitatively less prevalent. Evidence based treatment of invasive aspergillosis has become safer and more effective within the last ten years through the introduction of the new azoles and the echinocandines. Voriconazole has become the medication of choice for initial therapy. The efficacy of voriconazole is well documented, to include the treatment of disseminated infections of the central nervous system. Amphotericin B-desoxycholate is associated with definite side-effects in intravenous therapy. On the grounds of its substantial toxicity, the North American Infectious Disease Society's (IDSA) Guidelines of 2008 recommend amphotericin B-desoxycholate for regions with restricted resources only, which could be the case in underdeveloped countries. Liposomal amphotericin B in the daily standard dose of 3 mg/kg offers a rate of response similar to the one with voriconazole in the first-line treatment of invasive aspergillosis. However, a direct comparison with voriconazole on the basis of randomized studies is not available. As a secondary therapeutic treatment, in case of failure or intolerance of the primary treatment, caspofungin, micafungin and posaconazole have recently been under study. Both the echinocandines and posaconazole have proven effective in daily clinical practise. In refractory cases of invasive aspergillosis a combination therapy has been employed clinically. The results of prospective comparative controlled studies on combination therapy versus monotherapy will not be available until after 2010.