15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      1577. Particle Characterization of Nebulized Liposomal Amphotericin B and Its Use in the Treatment of Murine Pulmonary Aspergillosis

      abstract
      , MS, , MS, , MS, , PhD
      Open Forum Infectious Diseases
      Oxford University Press

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Immunocompromised patients are very susceptible to pulmonary aspergillosis causing 50% mortality with present treatments, indicating a need for improved therapy. To address this, we standardized a nebulization method for effectively delivering liposomal amphotericin B (AmBisome®, AmBi) into lungs of Aspergillus fumigatus-infected mice.

          Methods

          AmBi particle characterization was done with a Cascade particle impactor and a Schuco S5000 nebulizer containing 1.33 mg/mL AmBi. For in vivo studies, AmBi was nebulized (neb) into a 12 compartment chamber (one mouse/compartment), following immunosuppression with 28 mg/kg triamcinolone IP (d-3, -1, +1). Mice were challenged d0 with 9 x 10 6 A. fumigatus (ATCC#13073) and 4 hours post-challenge, divided into 5 groups ( n = 12/gp): 5 days of 20 min/day neb AmBi (Gp1), 5 days of 10 min/day neb AmBi (Gp2), 20 min/day neb AmBi days 0, 1, 3, 5, 7 (Gp 3), 5 days of intravenous(IV) AmBi 7.5 mg/kg/day (Gp4) and IV PBS (Gp5). Seven mice/gp were monitored for survival to d21 and lungs, livers, kidneys, spleens (5 mice/gp) analyzed for mean amphotericin B µg/g and CFU/g.

          Results

          87% of neb AmBi particles were between 0.43 mm to 3.3 mm allowing for drug penetration into 1°, 2° and terminal bronchi, bronchioles, and alveoli. This resulted in very good protection, with 20 min daily neb treatments (Gp1) giving 100% survival and 10 min daily neb treatments producing 71% survival (Gp2). There were no survivors in the PBS gp ( P < 0.02 vs. Gp1 and Gp2). Every other day neb AmBi or daily IV AmBi was less effective (43% survival). In addition, neb AmBi for 20 min (Gp1) yielded significantly lower fungal burden in lungs vs. all other AmBi treatments ( P < 0.02). While drug was detected in lungs of mice given 20 min of neb AmBi (2.6 µg/g), there was no drug detected in livers, kidneys or spleens of any mice given neb AmBi. In comparison, with IV AmBi, drug was detected in the lungs (7 µg/g), livers (204 µg/g), kidneys (38 µg/g), and spleens (114 µg/g).

          Conclusion

          Daily AmBi nebulization was an effective and potentially less nephrotoxic treatment for murine pulmonary aspergillosis since it achieved significantly lower tissue fungal burden and much better survival vs. daily IV AmBi, without delivering drug to the kidneys.

          Disclosures

          All authors: No reported disclosures.

          Related collections

          Author and article information

          Journal
          Open Forum Infect Dis
          Open Forum Infect Dis
          ofid
          Open Forum Infectious Diseases
          Oxford University Press (US )
          2328-8957
          October 2019
          23 October 2019
          23 October 2019
          : 6
          : Suppl 2 , IDWeek 2019 Abstracts
          : S576
          Affiliations
          Cal Poly Pomona , Pomona,California, California
          Article
          ofz360.1441
          10.1093/ofid/ofz360.1441
          6809417
          03224195-2218-4e21-b8bf-db5340f29f21
          © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

          This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

          History
          Page count
          Pages: 1
          Categories
          Abstracts
          Poster Abstracts

          Comments

          Comment on this article

          scite_
          0
          0
          0
          0
          Smart Citations
          0
          0
          0
          0
          Citing PublicationsSupportingMentioningContrasting
          View Citations

          See how this article has been cited at scite.ai

          scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

          Similar content309