amphotericin-b--deoxycholate-drug-combination and isavuconazole

Voriconazole, amphotericin B (AmB) formulations, and isavuconazole are all included in guideline recommendations for treatment of patients with invasive aspergillosis (IA) but the relative efficacy of isavuconazole versus AmB formulations has not been directly compared. We aimed to estimate the relative efficacy of isavuconazole compared with AmB deoxycholate (AmB-D), liposomal AmB (L-AmB), and voriconazole for the treatment of patients with proven/probable IA.. Nine literature databases were screened for randomized controlled trials comparing treatments with any of voriconazole, AmB-D, L-AmB and isavuconazole for treatment of proven/probable IA. Articles meeting the criteria were included in a meta-analysis to determine the efficacy of AmB-D, L-AmB and voriconazole relative to isavuconazole based on all-cause mortality (ACM) and overall response using a fixed-effects model.. Four articles were identified that compared L-AmB with AmB-D (Study 1), standard-dose L-AmB (3-5 mg/kg/day) with high-dose L-AmB (10 mg/kg/day; Study 2), voriconazole with AmB-D (Study 3), and isavuconazole with voriconazole (Study 4). In the network meta-analysis, isavuconazole was statistically superior to AmB-D on both ACM (odds ratio [95% credible intervals] shown as natural log, 1.00 [0.26, 1.74]) and overall response (-1.39 [-2.21, -0.63]). Differences between isavuconazole, and standard-dose L-AmB, high-dose L-AmB and voriconazole were not statistically significant for either ACM (0.18 [-1.17, 1.53], 0.50 [-1.11, 2.13] and 0.32 [-0.19, 0.84], respectively) or overall response (-0.99 [-2.21, 0.29], -0.89 [-2.41, 0.65] and 0.06 [-0.43, 0.57], respectively).. This data suggests that the efficacy of isavuconazole for treatment of IA is superior to AmB-D and comparable with both L-AmB and voriconazole.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Deoxycholic Acid; Drug Combinations; Humans; Network Meta-Analysis; Nitriles; Pyridines; Randomized Controlled Trials as Topic; Treatment Outcome; Triazoles; Voriconazole

Coccidioidal meningitis remains difficult to treat. The newer triazole, isavuconazole, has demonstrated efficacy in invasive fungal disease with less side effects than other azoles. We describe a case of refractory pediatric coccidioidal meningitis with disease stabilization and improvement on isavuconazole after failing treatment with other antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Child; Coccidioides; Coccidioidomycosis; Deoxycholic Acid; Drug Combinations; Humans; Meningitis, Fungal; Nitriles; Pyridines; Salvage Therapy; Triazoles; Voriconazole

Whether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or amphotericin B for the treatment of invasive molds infections has not been studied. Our in vitro combination studies showed that isavuconazole and micafungin are synergistically active against Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, and Cunninghamella bertholletiae. These results suggest that isavuconazole, in combination with micafungin, may have a role in the treatment of invasive aspergillosis and warrants further investigation.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Cunninghamella; Deoxycholic Acid; Drug Combinations; Drug Interactions; Echinocandins; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Mucormycosis; Nitriles; Pyridines; Triazoles