International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia

Ostrosky-Zeichner, Luis; Kontoyiannis, Dimitrios P.; Raffalli, John; Mullane, Kathleen M.; Vázquez, José Antonio; Anaissie, Elias; Lipton, Jeffrey H.; Jacobs, Paulette; Rensburg, J. H.Jansen Van; Rex, John H.; Lau, W.; Facklam, D.; Buell, Donald N.

doi:10.1007/s10096-005-0069-8

Cited by 50 publications

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“…Severely ill patients (who are often excluded from investigational studies because of renal or hepatic dysfunction, an estimated duration of survival of !5 days, or failure of prior antifungal therapy) were included in this trial [2,3,24].…”

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confidence: 99%

A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis

Pachl

Svoboda

Jacobs

et al. 2006

Clinical Infectious Diseases

274

151

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Background. Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.Methods. A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.Results. Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) Conclusions. Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.

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mentioning

confidence: 99%

A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis

Pachl

Svoboda

Jacobs

et al. 2006

Clinical Infectious Diseases

274

151

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“…A success rate of 83% in clearing candidal blood stream infections has been described using micafungin alone in 126 patients that included 20 children. 9 Our patient illustrates that substantial hepatotoxicity can be observed in association with administration of micafungin at a dose of 8 mg kg À1 daily in a premature infant. Further studies are needed to gain knowledge about the pharmacokinetics, pharmacodynamics, safety and efficacy of this drug in the pediatric population.…”

Section: Discussionmentioning

confidence: 80%

Hepatitis associated with micafungin use in a preterm infant

2009

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Micafungin is an echinocandin-class antifungal agent licensed for treatment of invasive disease in adults. The optimal dosing regimens have not been established for infants. We describe a premature infant who developed hepatitis and cholestasis during micafungin therapy initiated for protracted candidemia. Practitioners should be aware of this potential adverse effect if using micafungin in young patients. Journal of Perinatology (2009) 29, 320-322; doi:10.1038/jp.2008 Keywords: micafungin; hepatitis; infant; candidemia Introduction Optimal treatment of invasive fungal infection is an ongoing challenge for neonatologists, especially as the number of immunosuppressed and premature patients increases. Micafungin is a member of the echinocandin family of antifungals recently licensed for adults as an alternative or complement to traditional agents such as azoles and amphotericin B. 1 Optimal dosing and safety of this agent have not been established for infants and children.Case report A 44-day-old 2400 g former 28 week human immunodeficiency virus (HIV) and hepatitis C-exposed premature female was in her fourth week of nafcillin therapy for methicillin-susceptible Staphylococcus aureus bacteremia and right femoral osteomyelitis when she developed a new illness manifested as apnea requiring bag-mask ventilation. Blood, urine and cerebrospinal fluid (CSF) cultures were sent, and empirical treatment was initiated with vancomycin and gentamicin. After 1 day, her blood culture grew Candida albicans. The CSF and urine cultures were sterile. Therapy was changed to conventional amphotericin B (1 mg kg À1 per day) and her peripherally inserted central catheter (PICC) was removed. Head and renal ultrasounds were obtained and were normal. An echocardiogram showed a linear echodensity in the left innominate vein consistent with a cast at the location of the previous PICC line, and an ophthalmologic examination showed lesions consistent with Candida in the superior macula of the retina.Candidemia persisted, and on the seventh day of amphotericin B therapy, micafungin was added to the regimen at a dose of 8 mg kg À1 daily. The dose was chosen based on preliminary pharmacokinetic work by Heresi et al. 1 and expert opinion. Blood cultures became sterile 3 days later, and an ophthalmologic exam on day 7 of micafungin showed improvement in the retinal lesions.Before initiation of micafungin, the patient's serum aspartate aminotransaminase (AST) was 21 IU l À1 , serum alanine aminotransaminase (ALT) was 20 IU l À1 , total bilirubin was 1 mg per 100 ml and alkaline phosphatase was 268 IU l À1 . On day 2 of micafungin administration, the total bilirubin was 11.7 mg per 100 ml with direct bilirubin of 10.1 mg per 100 ml, but the AST and ALT were 25 and 28 IU l À1 , respectively ( Figure 1). On day 8 of micafungin administration, the AST had increased to 79 IU l À1 and the ALT to 39 IU l À1 . The total bilirubin was 12 mg per 100 ml and the conjugated bilirubin was 8.3 mg per 100 ml. The patient was transferred to our care on day 14 of m...

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“…En los estudios con un comparador diferente (anfotericina B o fl uconazol), se observa efi cacia clínica similar [27][28][29][30] . El principal escenario de estudio es en pacientes con candidiasis invasora o candidemia en la UCI [26][27][28][29][30][31][32] . En neutropenia febril se cuenta con evidencia clara respecto a la utilidad de caspofungina al ser comparada contra anfotericina B 33 .…”

Section: Ensayos Clínicos De Efectividadunclassified

“…En el caso de micafungina los eventos adversos más frecuentemente relacionados en varios estudios fueron fi ebre 6,3%, dolor abdominal 8,1%, náuseas 6,3%, diarrea 6,3% en pacientes con infección por VIH 39 . Otro estudio encontró trombocitopenia 2%, fi ebre 0,7%, fi brilación auricular 0,7%, trombofl ebitis 0,7% y aumento del nitró-geno ureico en sangre 0,7% 31 . Sin embargo, una revisión sistemática plantea que la ocurrencia de estos eventos es de aproximadamente 22 a 30% de los pacientes 45 .…”

Section: Efectos Adversosunclassified

Equinocandinas

2011

Rev. chil. infectol.

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EchinocandinsThe echinocandins, caspofugin, micafungin, and anidulafungin, are lipopeptides that inhibit fungal growth by binding to β -(1.3) d glucan synthase. This enzyme is responsible for the formation of the peptidoglycan cell wall, and it is essential in fungi such as Candida spp, but less important in the case of Aspergillus and Fusarium species. We review the history, pharmacology and clinical trials that have showed clinical effi cacy similar to amphotericin B for the management of fungal infections such as candidemia, invasive candidiasis and aspergillosis, even in cases refractory to initial treatment. These drugs have less toxicity and discontinuation is uncommonly required. Despite similar spectrum and tolerability, there are several pharmacological differences. Only a few clinical trials compare the clinical effi cacy between them and their clinical application cannot be generalized. However, the echinocandins have demonstrated clinical effi cacy in patients with invasive candidiasis and in others forms of systemic mycoses.

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International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia

Cited by 50 publications

References 0 publications

A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis

A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis

Hepatitis associated with micafungin use in a preterm infant

Equinocandinas

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