The frequency of
invasive fungal infections, and specifically invasive
aspergillosis, has increased in the last few decades. Despite the development of new
antifungal agents, these
infections are associated with high mortality, ranging from 40% to 80%, depending on the patient and the localization of the
infection. To reduce these figures, several therapeutic strategies have been proposed, including combination
therapy. Most of the available data on the efficacy of these combinations are from experimental models, in vitro data and retrospective observational studies or studies with a small number of patients that have included both patients in first-line treatment and those receiving rescue
therapy; in addition there are many patients with possible forms of
aspergillosis and few with demonstrated or probable forms. To date, there is no evidence that combination
therapy has significantly higher efficacy than monotherapy; however, combination
therapy could be indicated in severe forms of
aspergillosis, or forms with central nervous involvement or extensive pulmonary involvement with
respiratory insufficiency, etc. Among the combinations, the association of an
echinocandin--the group that includes
micafungin--with
voriconazole or
liposomal amphotericin B seems to show synergy. These combinations are those most extensively studied in clinical trials and therefore, although the grade of evidence is low, are recommended by the various scientific societies.