TY - JOUR
T1 - The fading boundaries between patient and environmental routes of triazole resistance selection in Aspergillus fumigatus
AU - Buil, Jochem B.
AU - Hare, Rasmus K.
AU - Zwaan, Bas J.
AU - Arendrup, Maiken C.
AU - Melchers, Willem J.G.
AU - Verweij, Paul E.
PY - 2019/8/22
Y1 - 2019/8/22
N2 - Aspergillus fumigatus is a saprobic fungus that may cause allergic syndromes, chronic pulmonary aspergillosis (CPA), and acute invasive aspergillosis (IA). Many patients suffering from aspergillus diseases benefit from antifungal therapy. Itraconazole, voriconazole, posaconazole, and isavuconazole have been shown to be the most effective compounds for prevention and treatment of the various aspergillus diseases. The use of alternative antifungal drugs, i.e., liposomal amphotericin B, is limited by toxicity and the echinocandins by fungistatic activity, while both also require intravenous access. As a consequence, the triazoles have become the recommended option for first-line therapy and chemoprophylaxis. Unfortunately, the effective use of triazoles has been threatened by the emergence of resistance in A. fumigatus. In voriconazole-treated patients, day 42 survival was 21% lower in voriconazole-resistant IA compared with voriconazole-susceptible infection. As the number of available drug classes is already very limited, some aspergillus diseases, such as central nervous system IA, are virtually untreatable if caused by a triazole-resistant isolate.
AB - Aspergillus fumigatus is a saprobic fungus that may cause allergic syndromes, chronic pulmonary aspergillosis (CPA), and acute invasive aspergillosis (IA). Many patients suffering from aspergillus diseases benefit from antifungal therapy. Itraconazole, voriconazole, posaconazole, and isavuconazole have been shown to be the most effective compounds for prevention and treatment of the various aspergillus diseases. The use of alternative antifungal drugs, i.e., liposomal amphotericin B, is limited by toxicity and the echinocandins by fungistatic activity, while both also require intravenous access. As a consequence, the triazoles have become the recommended option for first-line therapy and chemoprophylaxis. Unfortunately, the effective use of triazoles has been threatened by the emergence of resistance in A. fumigatus. In voriconazole-treated patients, day 42 survival was 21% lower in voriconazole-resistant IA compared with voriconazole-susceptible infection. As the number of available drug classes is already very limited, some aspergillus diseases, such as central nervous system IA, are virtually untreatable if caused by a triazole-resistant isolate.
U2 - 10.1371/journal.ppat.1007858
DO - 10.1371/journal.ppat.1007858
M3 - Article
C2 - 31437247
AN - SCOPUS:85071434743
SN - 1553-7366
VL - 15
SP - e1007858
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 8
ER -