In vitrosynergy of caspofungin with licensed and novel antifungal drugs against clinical isolates ofFusariumspp.

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.

DifferentialAspergillus lentulusEchinocandin Susceptibilities Are Fksp Independent

“…Similarly, CAS shows strong in vitro synergism with the calcineurin inhibitor tacrolimus (FK-506) against CAS-resistant Fusarium spp. (34), demonstrating an analogous need for calcineurin signaling in response to cell wall perturbation in these fungi. Since changes in chitin content are associated with the compensatory response to echinocandins, we wished to determine whether chitin could be associated with the differential echinocandin susceptibilities of A. lentulus.…”

A Clinical Review of Echinocandins in Pediatric Patients

“…and Penicillium spp. [20][21][22][23] This may provide a new treatment modality for difficult-to-treat infections, but more studies are needed to investigate the clinical utility of combination therapy.…”

Potent Activities of Luliconazole, Lanoconazole, and Eight Comparators against Molecularly Characterized Fusarium Species

“…Currently, European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) joint guidelines and most published studies suggest that early therapy with amphotericin B and voriconazole in conjunction with surgical debridement and reversal of immunosuppression is the treatment of choice for disseminated fusariosis (13)(14)(15). However, survival rates are low in these patient populations (ϳ30% or less), particularly among patients with constant immunosuppression (13)(14)(15)(16)(17). In keratitis cases, topical natamycin is used along with voriconazole as the mainstay of Fusarium treatment (18).…”