Anti-Pseudomonas aeruginosa Vaccines and Therapies: An Assessment of Clinical Trials

Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes high morbidity and mortality in cystic fibrosis (CF) and immunocompromised patients, including patients with ventilator-associated pneumonia (VAP), severely burned patients, and patients with surgical wounds. Due to the intrinsic and extrinsic antibiotic resistance mechanisms, the ability to produce several cell-associated and extracellular virulence factors, and the capacity to adapt to several environmental conditions, eradicating P. aeruginosa within infected patients is difficult. Pseudomonas aeruginosa is one of the six multi-drug-resistant pathogens (ESKAPE) considered by the World Health Organization (WHO) as an entire group for which the development of novel antibiotics is urgently needed. In the United States (US) and within the last several years, P. aeruginosa caused 27% of deaths and approximately USD 767 million annually in health-care costs. Several P. aeruginosa therapies, including new antimicrobial agents, derivatives of existing antibiotics, novel antimicrobial agents such as bacteriophages and their chelators, potential vaccines targeting specific virulence factors, and immunotherapies have been developed. Within the last 2–3 decades, the efficacy of these different treatments was tested in clinical and preclinical trials. Despite these trials, no P. aeruginosa treatment is currently approved or available. In this review, we examined several of these clinicals, specifically those designed to combat P. aeruginosa infections in CF patients, patients with P. aeruginosa VAP, and P. aeruginosa–infected burn patients.