More than 25 years ago combination of amphotericin B (AmB) and 5-fluorocytosine was shown to be more effective than AmB alone in the treatment of cryptococcal meningitis. Since then, the accumulation of evidence in using antifungal combinations for other invasive fungal infections has been slow. This was initially due to the controversy related to in vitro antagonism between azoles and polyenes and the lesser frequency of invasive fungal infections which were, then, treatable with early azoles such as fluconazole in case of candidiasis and amphotericin B that sufficiently provided coverage for most of mold infections. However, the clinical picture has significantly changed during the last two decades. First, the incidence and of invasive fungal infections has sharply increased and their epidemiology changed. Secondly, newer, broader-spectrum antifungals with previously non-existent mechanisms of effect have become commercially available. Disseminated infections caused by non-Candidal yeasts and not only Aspergillus spp., but also previously rarely seen non-Aspergillus mold infections have emerged as significant causes of morbidity and mortality among immunosuppressed patients. Since these infections are usually difficultto- treat and related mortality in infected patients remains to be very high, especially in those who are persistently immunosuppressed, the clinicians are tempted to use various newer antifungals with novel mechanism of action in combination in different clinical settings, especially in invasive aspergillosis. The rationale behind this rekindled interest is to achieve synergy and to a lesser extend, to reduce antifungal resistance. Although, there has been no controlled clinical trials comparing antifungal combinations with monotherapy so far, evidence gathered from small series and anectodal experience clearly indicates that antifungal combination therapy has become a clinical reality, particularly in those patients with severe immunosuppression and disseminated mould infections. The available data from above mentioned observations also pointed out that combinations of newly approved imidazoles (e.g. voriconazole) and echinocandins (e.g. caspofungin) with other agents are very unlikely to be antagonistic. Future studies are definitely required whether combination therapy with these new agents would improve survival and treatment outcome in the seriously hampered patients with life threatening fungal infections.
Full conference title:
16th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 16th (2006)