In vitro synergy of caspofungin with licensed and novel antifungal drugs against clinical isolates of Fusarium spp.

Itamar Shalit; Yona Shadkchan; Gabriel Mircus; Nir Osherov

doi:10.1080/13693780802232910

In vitro synergy of caspofungin with licensed and novel antifungal drugs against clinical isolates of Fusarium spp.

Itamar Shalit, Yona Shadkchan, Gabriel Mircus, Nir Osherov^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Combinations of caspofungin (CAS) with amphotericin-B (AMB), voriconazole (VRC), terbinafine (TRB) and tacrolimus (FK-506) were tested in vitro with 10 Fusarium isolates. MIC and minimal effective concentrations (MEC) were investigated in accord with the CLSI methodology. Drug interactions were assessed by the fractional inhibitory concentration index (FICI). Synergy occurred in 10/10, 9/10, 7/10 and 4/10 isolates with CAS/FK-506, CAS/TRB, CAS/AMB and CAS/VRC, respectively. Caspofungin MECs reached clinically attainable concentrations with FK-506 and TRB. Hyphal length and DiBAC staining demonstrated enhanced inhibition and killing with CAS/FK-506 and CAS/TRB. The combination of CAS/TRB and CAS/FK-506 is strongly synergistic in vitro against Fusarium spp. Our finding should be further studied in animal models of invasive infections caused by this fungus.

Original language	English
Pages (from-to)	457-462
Number of pages	6
Journal	Medical Mycology
Volume	47
Issue number	5
DOIs	https://doi.org/10.1080/13693780802232910
State	Published - 2009

Funding

Funders	Funder number
Tel Aviv University

Keywords

Caspofungin
Fusarium
Synergy
Tacrolimus
Terbinafine

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10.1080/13693780802232910

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title = "In vitro synergy of caspofungin with licensed and novel antifungal drugs against clinical isolates of Fusarium spp.",

abstract = "Combinations of caspofungin (CAS) with amphotericin-B (AMB), voriconazole (VRC), terbinafine (TRB) and tacrolimus (FK-506) were tested in vitro with 10 Fusarium isolates. MIC and minimal effective concentrations (MEC) were investigated in accord with the CLSI methodology. Drug interactions were assessed by the fractional inhibitory concentration index (FICI). Synergy occurred in 10/10, 9/10, 7/10 and 4/10 isolates with CAS/FK-506, CAS/TRB, CAS/AMB and CAS/VRC, respectively. Caspofungin MECs reached clinically attainable concentrations with FK-506 and TRB. Hyphal length and DiBAC staining demonstrated enhanced inhibition and killing with CAS/FK-506 and CAS/TRB. The combination of CAS/TRB and CAS/FK-506 is strongly synergistic in vitro against Fusarium spp. Our finding should be further studied in animal models of invasive infections caused by this fungus.",

keywords = "Caspofungin, Fusarium, Synergy, Tacrolimus, Terbinafine",

author = "Itamar Shalit and Yona Shadkchan and Gabriel Mircus and Nir Osherov",

note = "Funding Information: Source of funding: This work was supported by Tel-Aviv University internal funds to NO.",

year = "2009",

doi = "10.1080/13693780802232910",

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AU - Shalit, Itamar

AU - Shadkchan, Yona

AU - Mircus, Gabriel

AU - Osherov, Nir

N1 - Funding Information: Source of funding: This work was supported by Tel-Aviv University internal funds to NO.

PY - 2009

Y1 - 2009

N2 - Combinations of caspofungin (CAS) with amphotericin-B (AMB), voriconazole (VRC), terbinafine (TRB) and tacrolimus (FK-506) were tested in vitro with 10 Fusarium isolates. MIC and minimal effective concentrations (MEC) were investigated in accord with the CLSI methodology. Drug interactions were assessed by the fractional inhibitory concentration index (FICI). Synergy occurred in 10/10, 9/10, 7/10 and 4/10 isolates with CAS/FK-506, CAS/TRB, CAS/AMB and CAS/VRC, respectively. Caspofungin MECs reached clinically attainable concentrations with FK-506 and TRB. Hyphal length and DiBAC staining demonstrated enhanced inhibition and killing with CAS/FK-506 and CAS/TRB. The combination of CAS/TRB and CAS/FK-506 is strongly synergistic in vitro against Fusarium spp. Our finding should be further studied in animal models of invasive infections caused by this fungus.

AB - Combinations of caspofungin (CAS) with amphotericin-B (AMB), voriconazole (VRC), terbinafine (TRB) and tacrolimus (FK-506) were tested in vitro with 10 Fusarium isolates. MIC and minimal effective concentrations (MEC) were investigated in accord with the CLSI methodology. Drug interactions were assessed by the fractional inhibitory concentration index (FICI). Synergy occurred in 10/10, 9/10, 7/10 and 4/10 isolates with CAS/FK-506, CAS/TRB, CAS/AMB and CAS/VRC, respectively. Caspofungin MECs reached clinically attainable concentrations with FK-506 and TRB. Hyphal length and DiBAC staining demonstrated enhanced inhibition and killing with CAS/FK-506 and CAS/TRB. The combination of CAS/TRB and CAS/FK-506 is strongly synergistic in vitro against Fusarium spp. Our finding should be further studied in animal models of invasive infections caused by this fungus.

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KW - Synergy

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KW - Terbinafine

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In vitro synergy of caspofungin with licensed and novel antifungal drugs against clinical isolates of Fusarium spp.

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Keywords

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