ABSTRACT
Phage therapy has been suggested as a potential treatment for highly antibiotic-resistant bacteria, such as the species of the Burkholderia cepacia complex (BCC). To address this hypothesis, experimental B. cenocepacia respiratory infections were established in mice using a nebulizer and a nose-only inhalation device. Following infection, the mice were treated with one of five B. cenocepacia-specific phages delivered as either an aerosol or intraperitoneal injection. The bacterial and phage titers within the lungs were assayed 2 days after treatment, and mice that received the aerosolized phage therapy demonstrated significant decreases in bacterial loads. Differences in phage activity were observed in vivo. Mice that received phage treatment by intraperitoneal injection did not demonstrate significantly reduced bacterial loads, although phage particles were isolated from their lung tissue. Based on these data, aerosol phage therapy appears to be an effective method for treating highly antibiotic-resistant bacterial respiratory infections, including those caused by BCC bacteria.
Subject(s)
Bacteriophages , Burkholderia Infections/therapy , Burkholderia cepacia complex , Respiratory Tract Infections/therapy , Aerosols , Animals , Bacterial Load , Drug Resistance, Bacterial , Female , Immunocompromised Host , Injections, Intraperitoneal , Lung/virology , Mice , Mice, Inbred BALB C , Myoviridae , Treatment OutcomeABSTRACT
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.
