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Micafungin in the treatment of invasive candidiasis and invasive aspergillosis.

Wiederhold NP, Cota JM, Frei CR - Infect Drug Resist (2009)

Bottom Line: Dosage escalation studies have also demonstrated that doses much higher than those currently recommended may be administered without serious adverse effects.Clinically, micafungin has been shown to be efficacious for the treatment of invasive candidiasis and invasive aspergillosis.Furthermore, the clinical effectiveness of micafungin against these infections occurs without the drug interactions that occur with the azoles and the nephrotoxicity observed with amphotericin B formulations.

View Article: PubMed Central - PubMed

Affiliation: University of Texas at Austin College of Pharmacy, Austin, Texas, USA;

ABSTRACT
Micafungin is an echinocandin antifungal agent available for clinical use in Japan, Europe, and the United States. Through inhibition of β-1,3-glucan production, an essential component of the fungal cell wall, micafungin exhibits potent antifungal activity against key pathogenic fungi, including Candida and Aspergillus species, while contributing minimal toxicity to mammalian cells. This activity is maintained against polyene and azole-resistant isolates. Pharmacokinetic and pharmacodynamic studies have demonstrated linear kinetics both in adults and children with concentration-dependent activity observed both in vitro and in vivo. Dosage escalation studies have also demonstrated that doses much higher than those currently recommended may be administered without serious adverse effects. Clinically, micafungin has been shown to be efficacious for the treatment of invasive candidiasis and invasive aspergillosis. Furthermore, the clinical effectiveness of micafungin against these infections occurs without the drug interactions that occur with the azoles and the nephrotoxicity observed with amphotericin B formulations. This review will focus on the pharmacology, clinical microbiology, mechanisms of resistance, safety, and clinical efficacy of micafungin in the treatment of invasive candidiasis and invasive aspergillosis.

No MeSH data available.


Related in: MedlinePlus

Response rates of antifungal agents in clinical trials of invasive candidiasis. FLC: fluconazole, AMB: amphotercin B deoxycholate, CFG: caspofungin, AFG: anidulafungin, MFG: micafungin, LAMB: liposomal amphotericin B, MFG 100: micafungin 100 mg, MFG 150: micafungin 150 mg (Rex et al 1994; Mora-Duarte et al 2002; Kullberg et al 2005; Kuse et al 2007; Pappas et al 2007; Reboli et al 2007).
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f2-idr-1-063: Response rates of antifungal agents in clinical trials of invasive candidiasis. FLC: fluconazole, AMB: amphotercin B deoxycholate, CFG: caspofungin, AFG: anidulafungin, MFG: micafungin, LAMB: liposomal amphotericin B, MFG 100: micafungin 100 mg, MFG 150: micafungin 150 mg (Rex et al 1994; Mora-Duarte et al 2002; Kullberg et al 2005; Kuse et al 2007; Pappas et al 2007; Reboli et al 2007).

Mentions: In the two previously described studies, as well as other studies that have evaluated caspofungin and anidulafungin for the treatment of invasive fungal infections, a member of another antifungal class has been used as the active comparator. To date, only one clinical trial has directly compared two echinocandins for the treatment of invasive fungal infections. In this double-blind, non-inferiority study, patients were randomized to receive either micafungin 100 mg/day or 150 mg/day, or caspofungin, administered at 70 mg on the first day and 50 mg/day thereafter, for the treatment of invasive candidiasis/candidemia (Pappas et al 2007). Overall success, again defined as a favorable clinical and mycological response at the end of therapy, was similar among the three groups with 74% of patients randomized to micafungin 100 mg, 70% to micafungin 150 mg, and 71% in those who received caspofungin having a favorable outcome. Interestingly, a higher response rate was reported for the higher dose of micafungin in patients with infections caused by C. glabrata. However, this study was not sufficiently powered to assess differences among Candida species. These results demonstrate that micafungin is as effective as caspofungin for the treatment of invasive candidiasis/candidemia. Similar safety profiles among the treatment groups were also reported. Although a clear dose-response was observed in an early study that compared micafungin to fluconazole for the treatment of esophageal candidiasis, such an effect was not observed in this study as micafungin 100 mg/day was as effective as the higher dose of 150 mg/day. Overall, the response rates reported in the studies that have evaluated micafungin for invasive candidiasis/candidemia are similar to those observed for caspofungin and anidulafungin as well as other antifungal agents in clinical studies (Figure 2) (Rex et al 1994; Mora-Duarte et al 2002; Kullberg et al 2005; Reboli et al 2007).


Micafungin in the treatment of invasive candidiasis and invasive aspergillosis.

Wiederhold NP, Cota JM, Frei CR - Infect Drug Resist (2009)

Response rates of antifungal agents in clinical trials of invasive candidiasis. FLC: fluconazole, AMB: amphotercin B deoxycholate, CFG: caspofungin, AFG: anidulafungin, MFG: micafungin, LAMB: liposomal amphotericin B, MFG 100: micafungin 100 mg, MFG 150: micafungin 150 mg (Rex et al 1994; Mora-Duarte et al 2002; Kullberg et al 2005; Kuse et al 2007; Pappas et al 2007; Reboli et al 2007).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108724&req=5

f2-idr-1-063: Response rates of antifungal agents in clinical trials of invasive candidiasis. FLC: fluconazole, AMB: amphotercin B deoxycholate, CFG: caspofungin, AFG: anidulafungin, MFG: micafungin, LAMB: liposomal amphotericin B, MFG 100: micafungin 100 mg, MFG 150: micafungin 150 mg (Rex et al 1994; Mora-Duarte et al 2002; Kullberg et al 2005; Kuse et al 2007; Pappas et al 2007; Reboli et al 2007).
Mentions: In the two previously described studies, as well as other studies that have evaluated caspofungin and anidulafungin for the treatment of invasive fungal infections, a member of another antifungal class has been used as the active comparator. To date, only one clinical trial has directly compared two echinocandins for the treatment of invasive fungal infections. In this double-blind, non-inferiority study, patients were randomized to receive either micafungin 100 mg/day or 150 mg/day, or caspofungin, administered at 70 mg on the first day and 50 mg/day thereafter, for the treatment of invasive candidiasis/candidemia (Pappas et al 2007). Overall success, again defined as a favorable clinical and mycological response at the end of therapy, was similar among the three groups with 74% of patients randomized to micafungin 100 mg, 70% to micafungin 150 mg, and 71% in those who received caspofungin having a favorable outcome. Interestingly, a higher response rate was reported for the higher dose of micafungin in patients with infections caused by C. glabrata. However, this study was not sufficiently powered to assess differences among Candida species. These results demonstrate that micafungin is as effective as caspofungin for the treatment of invasive candidiasis/candidemia. Similar safety profiles among the treatment groups were also reported. Although a clear dose-response was observed in an early study that compared micafungin to fluconazole for the treatment of esophageal candidiasis, such an effect was not observed in this study as micafungin 100 mg/day was as effective as the higher dose of 150 mg/day. Overall, the response rates reported in the studies that have evaluated micafungin for invasive candidiasis/candidemia are similar to those observed for caspofungin and anidulafungin as well as other antifungal agents in clinical studies (Figure 2) (Rex et al 1994; Mora-Duarte et al 2002; Kullberg et al 2005; Reboli et al 2007).

Bottom Line: Dosage escalation studies have also demonstrated that doses much higher than those currently recommended may be administered without serious adverse effects.Clinically, micafungin has been shown to be efficacious for the treatment of invasive candidiasis and invasive aspergillosis.Furthermore, the clinical effectiveness of micafungin against these infections occurs without the drug interactions that occur with the azoles and the nephrotoxicity observed with amphotericin B formulations.

View Article: PubMed Central - PubMed

Affiliation: University of Texas at Austin College of Pharmacy, Austin, Texas, USA;

ABSTRACT
Micafungin is an echinocandin antifungal agent available for clinical use in Japan, Europe, and the United States. Through inhibition of β-1,3-glucan production, an essential component of the fungal cell wall, micafungin exhibits potent antifungal activity against key pathogenic fungi, including Candida and Aspergillus species, while contributing minimal toxicity to mammalian cells. This activity is maintained against polyene and azole-resistant isolates. Pharmacokinetic and pharmacodynamic studies have demonstrated linear kinetics both in adults and children with concentration-dependent activity observed both in vitro and in vivo. Dosage escalation studies have also demonstrated that doses much higher than those currently recommended may be administered without serious adverse effects. Clinically, micafungin has been shown to be efficacious for the treatment of invasive candidiasis and invasive aspergillosis. Furthermore, the clinical effectiveness of micafungin against these infections occurs without the drug interactions that occur with the azoles and the nephrotoxicity observed with amphotericin B formulations. This review will focus on the pharmacology, clinical microbiology, mechanisms of resistance, safety, and clinical efficacy of micafungin in the treatment of invasive candidiasis and invasive aspergillosis.

No MeSH data available.


Related in: MedlinePlus