Abstract

With respiratory infections accounting for significant morbidity and mortality, the issue of antibiotic resistance has added to the gravity of the situation. Treatment of pulmonary infections (bacterial pneumonia, cystic fibrosis-associated bacterial infections, tuberculosis) is more challenging with the involvement of multi-drug resistant bacterial strains, which act as etiological agents. Furthermore, with the dearth of new antibiotics available and old antibiotics losing efficacy, it is prudent to switch to non-antibiotic approaches to fight this battle. Phage therapy represents one such approach that has proven effective against a range of bacterial pathogens including drug resistant strains. Inhaled phage therapy encompasses the use of stable phage preparations given via aerosol delivery. This therapy can be used as an adjunct treatment option in both prophylactic and therapeutic modes. In the present review, we first highlight the role and action of phages against pulmonary pathogens, followed by delineating the different methods of delivery of inhaled phage therapy with evidence of success. The review aims to focus on recent advances and developments in improving the final success and outcome of pulmonary phage therapy. It details the use of electrospray for targeted delivery, advances in nebulization techniques, individualized controlled inhalation with software control, and liposome-encapsulated nebulized phages to take pulmonary phage delivery to the next level. The review expands knowledge on the pulmonary delivery of phages and the advances that have been made for improved outcomes in the treatment of respiratory infections.

Highlights

  • Respiratory tract infections (RTIs) represent a leading cause of suffering and death worldwide

  • Results showed that inhalable combination powder formulations of phage PEV20 and ciprofloxacin were stable and exhibited a strong synergistic antimicrobial killing effect against P. aeruginosa strains isolated from cystic fibrosis (CF) patients

  • Inhaled phage therapy has the potential to transform the prevention and treatment of bacterial respiratory infections, including those caused by antibiotic-resistant bacteria

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Summary

INTRODUCTION

Respiratory tract infections (RTIs) represent a leading cause of suffering and death worldwide. It has been reported that the total healthcare cost for treating CF patients ranges to as high as 50,000 USD per patient per year and this is largely due to repeated hospital stays and treatment costs to manage the bacterial infections associated with such conditions (Sansgiry et al, 2012; Angelis et al, 2015; Trend et al, 2017) This scenario is made worse by the decline in the effectiveness of current antibiotic therapies due to the rapid spread of resistant bacterial infections, which do not respond to traditional treatment protocols. The present review discusses the prospects of pulmonary phage therapy and its efficacy in treating various RTIs considering antimicrobial resistance It later details the major challenges and new advances made in delivering phages to the infection site for improved outcome and availability, with major recent studies supporting these developments.

INHALED PHAGE THERAPY: A NEW ERA OF THERAPEUTICS
Major Pulmonary Pathogens
Phage Against Pulmonary Pathogens
Pulmonary Phage Delivery
Main Findings
ADVANCES IN DELIVERY AND FORMULATIONS-INHALED PHAGE THERAPY
Electrospray for Controlled and Targeted Drug Delivery via Inhalation
Liposome Encapsulated Phage Preparation for Improved Pulmonary Delivery
Individualized Controlled Inhalation Technology
CONCLUSION
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