ABSTRACT
This review article discusses the development of respiratory therapeutics containing bacteriophages indicated for lung infections, specifically those that have become increasingly difficult to treat because of antibiotic resistance. Recent achievements and remaining problems are presented for each step necessary to develop a bacteriophage-containing dosage form for respiratory drug delivery, including selection of appropriate bacteriophages for therapy, processing and purification of phage preparations, formulation into a stable, solid dosage form, and delivery device selection. Safety and efficacy studies in animals and human subjects are also reviewed.
Subject(s)
Bacterial Infections/therapy , Bacteriophages , Biological Therapy/methods , Lung/microbiology , Respiratory Tract Infections/therapy , Administration, Inhalation , Animals , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/microbiology , Bacteriophages/pathogenicity , Drug Resistance, Bacterial , Humans , Respiratory Tract Infections/microbiology , VirulenceABSTRACT
In recent times, increased attention has been given to evaluating the efficacy of phage therapy, especially in scenarios where the bacterial infectious agent of interest is highly antibiotic resistant. In this regard, phage therapy is especially applicable to infections caused by the Burkholderia cepacia complex (BCC) since members of the BCC are antibiotic pan-resistant. Current studies in BCC phage therapy are unique from many other avenues of phage therapy research in that the investigation is not only comprised of phage isolation, in vitro phage characterization and assessment of in vivo infection model efficacy, but also adapting aerosol drug delivery techniques to aerosol phage formulation delivery and storage.
Subject(s)
Bacteriophages/physiology , Biological Therapy/methods , Burkholderia Infections/therapy , Burkholderia cepacia complex , Respiratory Tract Infections/therapy , Aerosols , Animals , Bacteriophages/genetics , Biological Therapy/trends , Burkholderia cepacia complex/virology , Freeze Drying , Humans , Myoviridae/genetics , Myoviridae/physiology , Podoviridae/genetics , Podoviridae/physiology , Powders , Siphoviridae/genetics , Siphoviridae/physiologyABSTRACT
The Burkholderia cepacia complex consists of nine phenotypically similar but genotypically distinct beta-proteobacteria that are metabolically diverse and highly antibiotic resistant. Because of this exceptional intrinsic antibiotic resistance, infections with B. cepacia complex members are difficult to treat clinically and new alternative therapies are required. One strategy that holds some promise is the use of naturally occurring antibacterial bacteriophages that could potentially bind to and lyse B. cepacia complex cells in vivo. Towards that end, we used enrichment techniques to isolate lytic and lysogenic bacteriophages specific to the B. cepacia complex. The newly isolated bacteriophages were characterized by host range analysis, electron microscopy, genome restriction analysis, and partial DNA sequencing. These isolates include a bacteriophage with one of the broadest host ranges yet identified for any bacteriophage specific to the B. cepacia complex, and the first description of bacteriophages capable of lysing B. ambifaria.