Chronic invasive sinus and intracerebral aspergillosis controlled by combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution

Ogawa, Taku; Matsumoto, Kana; Tsujimoto, Kazunori; Hishiya, Naokuni; Yamada, Yutaka; Uno, Kenji; Kasahara, Kei; Maeda, Koichi; Nario, Kazuhiko; Mikasa, Keiichi; Morita, Kunihiko

doi:10.1016/j.jiac.2014.08.010

Cited by 7 publications

(2 citation statements)

References 16 publications

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“…Because of the relatively limited efficacy of the current antifungal treatments, an exploration of alternative strategies against this difficult-to-treat infection is crucial. Combinations of antifungal agents are not common therapies but might be good alternatives for infections by resistant organisms or when the standard treatments fail (6)(7)(8)(9)(10)(11). Synergistic interactions of two drugs with different targets on the fungal cell can be more effective than each drug working alone.…”

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confidence: 99%

In Vivo Synergy of Amphotericin B plus Posaconazole in Murine Aspergillosis

Martín‐Vicente

Capilla

Guarro

2016

Antimicrob Agents Chemother

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Aspergillus fumigatus is the main mold causing invasive fungal infection that shows high mortality rates. Therapeutic failure and the increase in drug resistance make it necessary to explore alternative treatments for this infection. We have evaluated the efficacy of amphotericin B at 0.8 mg/kg or 0.3 mg/kg of body weight combined with 40 mg/kg of posaconazole against three A. fumigatus isolates in a murine model of disseminated infection. The combination of the polyene and the azole led to a greater increase in survival and a significantly greater reduction in tissue burden than monotherapies.A spergillus fumigatus is the most common mold causing invasive fungal infection (IFI) in immunocompromised patients (1), especially in those with hematological malignancies, with high mortality rates (2-4). Voriconazole (VRC) is the first-line therapy for the treatment of aspergillosis, but in patients with infections that are refractory to this drug, therapy options include other azoles such as itraconazole or posaconazole (PSC), lipid formulations of amphotericin B (LAMB), or echinocandins (5). Because of the relatively limited efficacy of the current antifungal treatments, an exploration of alternative strategies against this difficult-to-treat infection is crucial. Combinations of antifungal agents are not common therapies but might be good alternatives for infections by resistant organisms or when the standard treatments fail (6-11). Synergistic interactions of two drugs with different targets on the fungal cell can be more effective than each drug working alone. In addition, combined therapies can allow lower doses to be administered, with lower toxicity, faster cure, and probably lower costs. Since the efficacies of different antifungal combinations have been demonstrated by several studies in patients with aspergillosis (6, 7, 12), we were interested in evaluating the in vivo efficacy of the combination of amphotericin B (AMB) plus PSC against A. fumigatus. This combination had already been tested in a murine model of invasive aspergillosis caused by Aspergillus flavus (13), although no improvement over the PSC monotherapy was observed. Another study demonstrated the efficacy of suboptimal doses of VRC plus anidulafungin in a murine model of A. fumigatus infection (14), suggesting that combined therapies might have an important role as alternative treatments against systemic aspergillosis, allowing a reduction of the doses administered. One of the isolates tested in the present study (FMR 10528) had already been used in previous studies but showed a poor in vivo response to VRC when administered at 25 mg/kg of body weight despite having a low MIC (15, 16). The goals of this study were (i) to evaluate the efficacy of the combination of AMB plus PSC against isolates of A. fumigatus in a murine model of disseminated aspergillosis, comparing the results with those of the corresponding monotherapies and VRC, (ii) to investigate the presence of CYP51A gene mutations that might explain the poor in vivo response of such a...

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confidence: 99%

In Vivo Synergy of Amphotericin B plus Posaconazole in Murine Aspergillosis

Martín‐Vicente

Capilla

Guarro

2016

Antimicrob Agents Chemother

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“…In another research, it was found that combination therapy (MCF and daily dose of oral 400 mg itraconazole) can be promising alternative for treatment of fatal IA of the sinus [39].…”

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confidence: 99%

Echinocandins Versus Dated Antifungals in Combination Against Opportunistic Mycotic Infections

Narwal¹,

Balhara²,

Chaudhary³

et al. 2017

Asian J Pharm Clin Res

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Scientific and clinical reports globally demonstrated that the opportunistic mycotic infections are at major risk to the human fitness. In the past few decades, the development of resistance in microbes to existing antifungals has emphasized on the search of new antimycotic drugs. As a matter of fact, "echinocandins" are new categories of broad-spectrum antifungal enlighten a hope in this direction. Echinocandins are bulky lipopeptides that inhibit the production of β-[1,3]-glucan "a major constituent of fungal cell wall" which ultimately leads to the death of fungal pathogens. In vitro as well as in vivo published reports have demonstrated that the echinocandins exhibit fungicidal activity against most Candida spp., while fungistatic against Aspergillus spp. and exclusively found to be more effective when tested in combination with polyenes/azoles. The present article is expert views on the recent and historical literature available on the antifungal therapies with accessing their impact on the human health. Emphasis is given to the utility of the echinocandins a potental antifungal agent by discussing recent examples of clinical and laboratory studies including the use of improved proteomics approaches to know a bit more about the interaction of human host and fungal pathogens.

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Fungal Infections of the Central Nervous System

Carod-Artal

2017

CNS Infections

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Chronic invasive sinus and intracerebral aspergillosis controlled by combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution

Cited by 7 publications

References 16 publications

In Vivo Synergy of Amphotericin B plus Posaconazole in Murine Aspergillosis

In Vivo Synergy of Amphotericin B plus Posaconazole in Murine Aspergillosis

Echinocandins Versus Dated Antifungals in Combination Against Opportunistic Mycotic Infections

Fungal Infections of the Central Nervous System

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