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001-es BibID:BIBFORM079570
035-os BibID:(PMID)31303773
Első szerző:Prépost Eszter
Cím:Efficacy of humanized single large doses of caspofungin on the lethality and fungal tissue burden in a deeply neutropenic murine model against Candida albicans and Candida dubliniensis / Eszter Prépost, Zoltán Tóth, David S. Perlin, Rudolf Gesztelyi, Gábor Kardos, Renátó Kovács, Fruzsina Nagy, Lajos Forgács, László Majoros
Dátum:2019
ISSN:1178-6973
Megjegyzések:BACKGROUND: Echinocandins are the first-line therapy for treatment of invasive Candida infections, but the mortality rate remains high, calling for novel strategies. Giving single larger echinocandin doses infrequently is an alternative regimen. Our aim was to test this novel approach in a neutropenic murine model. MATERIALS AND METHODS: We compared the in vivo efficacy of single 10 and 40 mg/kg of caspofungin (2.5x and 10x the normal humanized dose) to that of the same cumulative doses of daily 2 and 8 mg/kg doses for 5 days against 2 each of wild-type C. albicans and C. dubliniensis as well as echinocandin resistant C. albicans. As a comparator, we tested daily 1 mg/kg amphotericin B. RESULTS: In lethality experiments, all caspofungin and amphotericin B regimens improved survival against wild-type C. albicans and C. dubliniensis clinical isolates (P<0.0001) and decreased the mean fungal kidney burdens of both species compared to controls. However, fungal kidney burden decreases were not always statistically significant, especially with single 10 or 40 mg/kg caspofungin doses. Amphotericin B was the least active drug against wild-type C. albicans. Against echinocandin-resistant strains, monodose 40 mg/kg caspofungin and 1 mg/kg of daily amphotericin B were effective in lethality experiments. Although, significant kidney CFU decreases were never found, except for amphotericin B against one of the isolates (p<0.05 at day 3 and p<0.001 at day 6). CONCLUSION: Single 40 mg/kg caspofungin and 1 mg/kg amphotericin B proved to be effective in the lethality experiments against wild-type and echinocandin-resistant C. albicans and wild-type C. dubliniensis. This was not always shown regarding fungal tissue burdens. Single caspofungin doses used in mice in this study are attainable in humans as well, suggesting a potential place of this dosing strategy not only in prevention but also in curative treatment of evolved invasive Candida infections.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Candida albicans complex
echinocandin resistance
fungal tissue burden
humanized caspofungin doses
intermittent dosing regimen of echinocandins
Megjelenés:Infection and Drug Resistance. - 12 (2019), p. 1805-1814. -
További szerzők:Tóth Zoltán (1990-) (molekuláris biológus) Perlin, David (1958-) (Biológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus) Kardos Gábor (1974-) (szakorvos, klinikai mikrobiológus) Kovács Renátó László (1987-) (molekuláris biológus) Nagy Fruzsina (1991-) (molekuláris biológus) Forgács Lajos (1954-) (agrármérnök-kutató) Majoros László (1966-) (szakorvos, klinikai mikrobiológus)
Pályázati támogatás:EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
TÁMOP 4.2.4. A/2-11-1-2012-0001
TÁMOP
ÚNKP-18-3
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