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Enhanced activity of antifungal drugs by lysozyme against Cryptococcus neoformans
Author(s) -
Nakamura Y.,
Kano R.,
Watanabe S.,
Takahashi H.,
Hasegawa A.
Publication year - 1998
Publication title -
mycoses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 69
eISSN - 1439-0507
pISSN - 0933-7407
DOI - 10.1111/j.1439-0507.1998.tb00324.x
Subject(s) - cryptococcus neoformans , itraconazole , fluconazole , terbinafine , lysozyme , microbiology and biotechnology , broth microdilution , minimum inhibitory concentration , amphotericin b , chemistry , cryptococcosis , antifungal drug , pharmacology , biology , antifungal , antimicrobial , biochemistry
Summary. The in vitro susceptibility of 16 isolates of Cryptococcus neoformans to three antifungal drugs and lysozyme in combination was determined using an urea broth microdilution method. The antifungal activities of each drug alone against 16 isolates of Cr. neoformans were determined as mean minimal inhibitory concentrations (MICs). MICs of fluconazole, itraconazole and terbinafine were 2.0 μg ml ‐1 , 0.004 μg ml ‐1 and 0.25 μg ml ‐1 , respectively. Lysozyme alone inhibited the growth of Cr. neoformans in a dose‐dependent manner, although the lysozyme was unable to kill the cells of Cr. neoformans at the highest concentration of 20 μml ‐1 . The mean MICs of fluconazole, itraconazole and terbinafine in combination with lysozyme were 0.13 μg ml ‐1 , 0.004 μg ml ‐1 and 0.03 μg ml ‐1 respectively. The antifungal activity of fluconazole and terbinafine in combination with lysozyme against Cr. neoformans was greatly enhanced compared with that of each drug alone. Itraconazole was unable to enhance the antifungal activity, as it demonstrated higher activity against Cr. neoformans when alone rather than in combination. Lysozyme was confirmed to enhance the antifungal activity of fluconazole and terbinafine in vitro. Zusammenfassung Die Empfindlichkeit von 16 Cryptococcus neoformans‐Isolaten für 3 Antimykotika allein und in Kombination mit Lysozym wurde in vitro im Harnstoff‐Mikrodilutionstest untersucht. Die minimale Hemmoknzentration (MHK) für Fluconazol, Itraconazol und Terbinafin jeweils allein betrug 2.0 μg ml ‐1 , 0.004 μg ml ‐1 bzw. 0.25 μg ml ‐1 . Lysozym allein hemmte das Wachstum von Cr. neoformans dosisabhängig, obgleich Lysozym nicht in der Lage war, den Pilz in der höchsten Konzentration von 20 μg ml ‐1 abzutöten. Die mittleren MHKs von Fluconazol, Itraconazol und Terbinafin in Kombination mit Lysozym betrugen 0.13 μg ml ‐1 , 0.004 μg ml ‐1 baz. 0.03 μg ml ‐1 . Die antimyzetische Aktivität von Fluconazol und Terbinafin war also in Kombination mit Lysozym für Cr. neoformans erheblich verstärkt gegenüber der Wirkung eines jeden Antimykotikums allein. Lysozym trägt offensichtlich neben seiner sonstigen Rolle in der Infektabwehr einen synergistischen Effekt zur antimykotischen Chemotherapie bei.