Aerosol antibiotics in cystic fibrosis.

Respir Care. 2009 May;54(5):658-70.

Aerosol antibiotics in cystic fibrosis.

Geller DE.

Aerosol Research Laboratory and Cystic Fibrosis Center, Nemours Children's Clinic, 496 S Delaney Avenue, Suite 406A, Orlando FL 32801. dgeller'nemours.org.

Chronic airways infection and inflammation is the greatest source of morbidity and mortality in cystic fibrosis (CF) patients. Many organisms can be found in the lower respiratory tract of CF patients, but infection with mucoid Pseudomonas aeruginosa is common, is associated with poorer outcomes, and is the main target for antimicrobial strategies in CF. Aerosol antibiotics achieve high local concentrations in the airways, reduce systemic toxicity, and have been used successfully for chronic suppressive treatment for established P. aeruginosa infections. Eradication of early P. aeruginosa airway infection has also been tried with aerosol antibiotics, though the ideal treatment strategy is still being investigated. There are several variables to consider when choosing an antibiotic formulation to develop for topical inhalation. Tobramycin solution for inhalation (TSI) is currently the only approved inhaled antibiotic in the United States. The time burden for patients to administer TSI by jet nebulizer is substantial, so efforts have focused on more efficient, faster delivery methods. Novel formulations of aerosol antibiotics are being studied for CF, including beta-lactams, fluoroquinolones and aminoglycosides. Phase-3 studies of aztreonam lysinate for inhalation delivered via a proprietary eFlow nebulizer showed improved outcomes and a short (< 3 min) delivery time. Liposome formulations are being studied as a way to penetrate mucoid biofilms and prolong the residence time of the antibiotic in the lungs. Light, porous, dry-powder formulations are also in clinical trials to reduce delivery time. These new formulations and delivery systems promise to expand our armamentarium against microbes while reducing the time burden for patients.

PMID: 19393109 [PubMed - in process]

The antimicrobial efficacy of sustained release silver–carbene complex-loaded l-tyrosine polyphosphate nanoparticles

Khadijah M. Hindi^a, Andrew J. Ditto^b, Matthew J. Panzner^a, Douglas A. Medvetz^a, Daniel S. Han^c, Christine E. Hovis^c, Julia K. Hilliard^c, Jane B. Taylor^c, Yang H. Yun^{b, ,} , Carolyn L. Cannon^{c, ,} and Wiley J. Youngs^{a, ,}

^aDepartment of Chemistry, University of Akron, Akron, OH 44325-3601, USA

^bDepartment of Biomedical Engineering, University of Akron, Akron, OH 44325-0302, USA

^cDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MI 63110-1002, USA

Received 19 January 2009;

accepted 17 March 2009.

Available online 23 April 2009.

The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver–carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into l-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period.



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