Feasibility, tolerability, and outcomes of nebulized liposomal amphotericin B for Aspergillus infection prevention in lung transplantation

Monforte, Vı́ctor; Ussetti, Piedad; Gavaldá, Joan; Bravo, Carles; Laporta, Rosalía; Len, Óscar; Garcı́a-Gallo, C. López; Tenorio, Luis Enrique David; Solé, Joan; Román, Antonio

doi:10.1016/j.healun.2009.11.603

Cited by 86 publications

(101 citation statements)

References 39 publications

(27 reference statements)

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“…Therefore, for the agents used for prophylaxis or treatment of infection confined to the airspace, concentrations in epithelial lining fluid (ELF) and within pulmonary alveolar macrophages are of direct importance. The inhalation of aerosolized amphotericin B formulations is a potential option for prophylaxis (133,134,135). Antifungal drug concentrations within ELF after aerosol inhalation or systemic administration were recently reviewed (12).…”

Section: Lungmentioning

confidence: 99%

Tissue Penetration of Antifungal Agents

Troke²,

2014

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SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection.

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Section: Lungmentioning

confidence: 99%

Tissue Penetration of Antifungal Agents

Troke²,

2014

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“…For example, oral micro-emulsion formulations have been successfully developed for cyclosporine, a highly lipophilic and poorly aqueous soluble drug in order to improve its oral absorption and reduce variations in its absorption (Kim et al, 1997;Cooney et al, 1998). The potential of liposomes and micro-emulsions as drug delivery carriers for the treatment of various topical and systemic fungal infections with several antifungal drugs such as amphotericin B, fluconazole, miconazole and griseofulvin has been proved in the literature (Peira et al, 2008;Pestana et al, 2008;Bachhav & Patravale, 2009;Monforte et al, 2010;Sheikh et al, 2010;Aggarwal & Goindi, 2012;Fauvel et al, 2012;Aggarwal et al, 2013). Topical liposomes and micro-emulsions offered several advantages as drug delivery vehicles such as enhanced skin permeation, enhanced therapeutic efficacy/bioavailability, avoidance of hepatic first pass metabolism and systemic adverse effects (Bachhav & Patravale, 2009;Sheikh et al, 2010;Aggarwal & Goindi, 2012;Aggarwal et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Comparative topical delivery of antifungal drug croconazole using liposome and micro-emulsion-based gel formulations

2013

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“…In two separate studies, nebulized liposomal amphotericin B was compared with nonliposomal amphotericin B deoxycholate. In both studies, rates of invasive Aspergillus infections were low and comparable between the two treatment groups, but the liposomal form was better tolerated (42,43). Inhaled antifungal agents have also been used as adjunctive agents to systemic antifungals in patients with devascularized anastomotic infections caused by Aspergillus or Candida spp.…”

Section: Ventilator-associated Pneumoniamentioning

confidence: 99%

“…Given the high mortality rates associated with invasive Aspergillus infections, routine antifungal prophylaxis is common but not universally adopted (41). Nebulized amphotericin B has been investigated as antifungal prophylaxis in a few nonrandomized, comparative studies (42)(43)(44). In two separate studies, nebulized liposomal amphotericin B was compared with nonliposomal amphotericin B deoxycholate.…”

Section: Ventilator-associated Pneumoniamentioning

confidence: 99%

Inhaled Antibiotics for Lower Airway Infections

2014

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Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade.Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilatorassociated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

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Feasibility, tolerability, and outcomes of nebulized liposomal amphotericin B for Aspergillus infection prevention in lung transplantation

Cited by 86 publications

References 39 publications

Tissue Penetration of Antifungal Agents

Tissue Penetration of Antifungal Agents

Comparative topical delivery of antifungal drug croconazole using liposome and micro-emulsion-based gel formulations

Inhaled Antibiotics for Lower Airway Infections

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