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001-es BibID:	BIBFORM111279
035-os BibID:	(cikkazonosító)1365 (Scopus)85160446980 (WoS)000997179700001
Első szerző:	Adnan, Awid (orvos)
Cím:	In Vitro Killing Activities of Anidulafungin and Micafungin with and without Nikkomycin Z against Four Candida auris Clades / Adnan Awid, Borman Andrew M., Tóth Zoltán, Forgács Lajos, Kovács Renátó, Balázsi Dávid, Balázs Bence, Udvarhelyi Gergely, Kardos Gábor, Majoros László
Dátum:	2023
ISSN:	1999-4923
Megjegyzések:	Candida auris is a multidrug-resistant pathogen against which echinocandins are the drug of choice. However, information on how the chitin synthase inhibitor nikkomycin Z influences the killing activities of echinocandins against C. auris is currently lacking. We determined the killing activities of anidulafungin and micafungin (0.25, 1, 8, 16 and 32 mg/L each) with and without nikkomycin Z (8 mg/L) against 15 isolates representing four C. auris clades (South Asian n = 5; East Asian n = 3; South African n = 3; South American n = 4, two of which were of environmental origin). Two and one isolates from the South Asian clade harbored mutations in the hot-spot 1 (S639Y and S639P) and 2 (R1354H) regions of the FKS1 gene, respectively. The anidulafungin, micafungin and nikkomycin Z MIC ranges were 0.015-4, 0.03-4 and 2->16 mg/L, respectively. Anidulafungin and micafungin alone exerted weak fungistatic activity against wild-type isolates and the isolate with a mutation in the hot-spot 2 region of FKS1 but was ineffective against the isolates with a mutation in the hot-spot 1 region. The nikkomycin Z killing curves were always similar to their respective controls. Twenty-two of sixty (36.7%) anidulafungin plus nikkomycin Z and twenty-four of sixty (40%) micafungin plus nikkomycin Z combinations produced at least 100-fold decreases in the CFUs (synergy), with a 41.7% and 20% fungicidal effect, respectively, against wild-type isolates. Antagonism was never observed. Similar results were found with the isolate with a mutation in hot-spot 2 of FKS1, but the combinations were ineffective against the two isolates with prominent mutations in hot-spot 1 of FKS1. The simultaneous inhibition of ?-1,3 glucan and chitin synthases in wild-type C. auris isolates produced significantly greater killing rates than either drug alone. Further studies are warranted to verify the clinical efficacy of echinocandin plus nikkomycin Z combinations against echinocandin susceptible C. auris isolates.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Pharmaceutics. - 15 : 5 (2023), p. 1-16. -
További szerzők:	Borman, Andrew M. Tóth Zoltán (1990-) (molekuláris biológus) Forgács Lajos Kovács Renátó László (1987-) (molekuláris biológus) Balázsi Dávid Balázs Bence (1991-) (PhD hallgató) Udvarhelyi Gergely Kardos Gábor (1974-) (szakorvos, klinikai mikrobiológus) Majoros László (1966-) (szakorvos, klinikai mikrobiológus)
Pályázati támogatás:	NKFIH FK138462 OTKA UNKP- 21-5 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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