Current and future therapies for Pseudomonas aeruginosa infection in patients with cystic fibrosis

• Published in: FEMS microbiology letters 2017-08, Vol.364 (14)
• Main Authors: Smith, Wynne D., Bardin, Emmanuelle, Cameron, Loren, Edmondson, Claire L., Farrant, Katie V., Martin, Isaac, Murphy, Ronan A., Soren, Odel, Turnbull, Andrew R., Wierre-Gore, Natasha, Alton, Eric W., Bundy, Jacob G., Bush, Andrew, Connett, Gary J., Faust, Saul N., Filloux, Alain, Freemont, Paul S., Jones, Andrew L., Takats, Zoltan, Webb, Jeremy S., Williams, Huw D., Davies, Jane C.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Alginic acid; Allyl Compounds - therapeutic use; Amikacin; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antibiotics; beta-Lactamases - biosynthesis; beta-Lactamases - genetics; Biofilms; Biofilms - drug effects; Biomarkers; Chronic infection; Cysteamine; Cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - drug therapy; Cystic Fibrosis - microbiology; Drug Resistance, Multiple, Bacterial; Efflux; Formulations; Fosfomycin; Gallium; Gram-negative bacteria; Humans; Immune clearance; Immunotherapy; Immunotherapy - methods; Infections; Levofloxacin; Microbiology; Morbidity; Nitric oxide; Pathogens; Porins; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - enzymology; Pseudomonas Infections - complications; Pseudomonas Infections - diagnosis; Pseudomonas Infections - microbiology; Respiratory tract; Sulfides - therapeutic use; Tobramycin
• ISSN: 1574-6968; 0378-1097; 1574-6968
• DOI: 10.1093/femsle/fnx121

Abstract Pseudomonas aeruginosa opportunistically infects the airways of patients with cystic fibrosis and causes significant morbidity and mortality. Initial infection can often be eradicated though requires prompt detection and adequate treatment. Intermittent and then chronic infection occurs in the majority of patients. Better detection of P. aeruginosa infection using biomarkers may enable more successful eradication before chronic infection is established. In chronic infection P. aeruginosa adapts to avoid immune clearance and resist antibiotics via efflux pumps, β-lactamase expression, reduced porins and switching to a biofilm lifestyle. The optimal treatment strategies for P. aeruginosa infection are still being established, and new antibiotic formulations such as liposomal amikacin, fosfomycin in combination with tobramycin and inhaled levofloxacin are being explored. Novel agents such as the alginate oligosaccharide OligoG, cysteamine, bacteriophage, nitric oxide, garlic oil and gallium may be useful as anti-pseudomonal strategies, and immunotherapy to prevent infection may have a role in the future. New treatments that target the primary defect in cystic fibrosis, recently licensed for use, have been associated with a fall in P. aeruginosa infection prevalence. Understanding the mechanisms for this could add further strategies for treating P. aeruginosa in future. This provides an overview of current and emerging treatments for Pseudomonas aeruginosa airway infection in cystic fibrosis patients, and explains the treatments in the context of the underpinning basic science.