Liposomal nystatin (L-NYS) in therapy of pulmonary aspergillosis refractory to conventional amphotericin B in cancer patients

Krupova, Y.; Mistrík, Martin; Bojtárová, Eva; Sejnová, Daniela; Ilavská, I.; Krčméry, V.

doi:10.1007/s005200000194

Cited by 8 publications

(5 citation statements)

References 5 publications

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“…Liposomal nystatin cured 4 patients, and all 5 had previously elevated serum creatinine levels return to normal [131]. A phase II trial noted that 7 of 16 evaluable patients with amphotericin B-refractory IA were alive on day 30 after treatment with 4 mg/kg/day liposomal nystatin [132].…”

Section: Polyenesmentioning

confidence: 99%

Review of Newer Antifungal and Immunomodulatory Strategies for Invasive Aspergillosis

2003

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The incidence of invasive aspergillosis is markedly increasing, and mortality remains dismal. Previously there were only 2 antifungals with activity against Aspergillus, but over the last few years there has been an explosion of newer agents and reformulations of older antifungals. Exploration has also begun with immunotherapy, with use of cytokines and granulocyte transfusions alone or in combination with antifungal therapy. This review will detail the available in vitro, in vivo, and clinical experience with the newer antifungal and immunomodulatory therapies in development for treatment of invasive aspergillosis.

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Section: Polyenesmentioning

confidence: 99%

Review of Newer Antifungal and Immunomodulatory Strategies for Invasive Aspergillosis

2003

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“…This study has contemporary clinical relevance, since nystatin has, in recent years, undergone reformulation into lipid carriers (6,7,10,12,20)-in similarity to the lipid formulations of amphotericin B. Indeed, intravenous liposomal nystatin has undergone early-phase clinical development (2).…”

Section: Vol 49 2005 Notes 3547mentioning

confidence: 99%

“…The incorporation of nystatin (and amphotericin B) into lipid carriers could create hindrance that prevents interaction between the polyene and TLR2 (15,16). In the only clinical data reported, only one of five patients receiving liposomal nystatin developed fever, chills, and dyspnea (10).…”

Section: Vol 49 2005 Notes 3547mentioning

confidence: 99%

Nystatin Induces Secretion of Interleukin (IL)-1β, IL-8, and Tumor Necrosis Factor Alpha by a Toll-Like Receptor-Dependent Mechanism

Razonable

Hénault

Watson

et al. 2005

Antimicrob Agents Chemother

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“…Efficacy has been shown for experimental infections including aspergillosis: liposomal nystatin at doses of 2 and 4 mg/kg/day, but not at 1 mg/kg/day, prolonged survival for neutropenic rabbits and reduced tissue fungal burden (8). In an experimental murine aspergillosis study, liposomal nystatin at a dose of 5 mg/kg given four times within the first week of infection was as effective as liposomal amphotericin B and more effective than amphotericin B deoxycholate and amphotericin B lipid complex (7 include a phase I maximal-tolerated-dose study, a compassionate-use study, and phase II and III trials for candidemia, for empirical therapy of persistent febrile neutropenia, and for cryptococcal meningitis (2,14,20). Doses used in clinical trials ranged from 2 to 4 mg/kg for empirical therapy of persistent febrile neutropenia and for candidemia (23,26).…”

mentioning

confidence: 99%

“…Clinical studies are very limited and have not yet been published. They include a phase I maximal-tolerated-dose study, a compassionate-use study, and phase II and III trials for candidemia, for empirical therapy of persistent febrile neutropenia, and for cryptococcal meningitis (2,14,20). Doses used in clinical trials ranged from 2 to 4 mg/kg for empirical therapy of persistent febrile neutropenia and for candidemia (23,26 …”

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confidence: 99%

Liposomal Nystatin in Patients with Invasive Aspergillosis Refractory to or Intolerant of Amphotericin B

Offner

Krčméry

Boogaerts

et al. 2004

Antimicrob Agents Chemother

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We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.Mold infections continue to be an important cause of death for patients with leukemia, allogeneic hematopoietic stem cell transplantation, and advanced stages of malignancy. The mortality rate of invasive aspergillosis (IA) ranges from 40 to 90% depending on the degree of underlying immune suppression and the institution of early therapy (5,16).Until the recent approval of voriconazole, standard treatment of IA consisted of intravenous amphotericin B given at doses of at least 1 mg/kg of body weight/day (11, 24). Amphotericin B is associated with considerable toxicity and frequent treatment failure, particularly in the case of advanced disease and prolonged neutropenia. The liposomal formulation of amphotericin B has allowed the administration of more than fivefold doses of the drug with considerable improvement in the safety profile (15,25).The liposomal encapsulation technique can, however, be extended to other antifungal agents that were previously excluded for treatment of systemic fungal infections due to the lack of a well-tolerated intravenous formulation. Nystatin is a naturally occurring product of Streptomyces noursei that has been used as a topical fungicidal drug since the 1950s. It is active against Candida, Cryptococcus, Histoplasma, Blastomyces, and Aspergillus spp. and has a spectrum of antifungal activity similar to that of amphotericin B (1,4,13,22).Early attempt...

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Liposomal nystatin (L-NYS) in therapy of pulmonary aspergillosis refractory to conventional amphotericin B in cancer patients

Cited by 8 publications

References 5 publications

Review of Newer Antifungal and Immunomodulatory Strategies for Invasive Aspergillosis

Review of Newer Antifungal and Immunomodulatory Strategies for Invasive Aspergillosis

Nystatin Induces Secretion of Interleukin (IL)-1β, IL-8, and Tumor Necrosis Factor Alpha by a Toll-Like Receptor-Dependent Mechanism

Liposomal Nystatin in Patients with Invasive Aspergillosis Refractory to or Intolerant of Amphotericin B

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