Cystic Fibrosis: Recent Insights into Inhaled Antibiotic Treatment and Future Perspectives

Abstract

Although new inhaled antibiotics have profoundly improved respiratory diseases in cystic fibrosis (CF) patients, lung infections are still the leading cause of death. Inhaled antibiotics, i.e., colistin, tobramycin, aztreonam lysine and levofloxacin, are used as maintenance treatment for CF patients after the development of chronic Pseudomonas aeruginosa (P. aeruginosa) infection. Their use offers advantages over systemic therapy since a relatively high concentration of the drug is delivered directly to the lung, thus, enhancing the pharmacokinetic/pharmacodynamic parameters and decreasing toxicity. Notably, alternating treatment with inhaled antibiotics represents an important strategy for improving patient outcomes. The prevalence of CF patients receiving continuous inhaled antibiotic regimens with different combinations of the anti-P. aeruginosa antibiotic class has been increasing over time. Moreover, these antimicrobial agents are also used for preventing acute pulmonary exacerbations in CF. In this review, the efficacy and safety of the currently available inhaled antibiotics for lung infection treatment in CF patients are discussed, with a particular focus on strategies for eradicating P. aeruginosa and other pathogens. Moreover, the effects of long-term inhaled antibiotic therapy for chronic P. aeruginosa infection and for the prevention of pulmonary exacerbations is reviewed. Finally, how the mucus environment and microbial community richness can influence the efficacy of aerosolized antimicrobial agents is discussed.

Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against Pseudomonas aeruginosa

“…In this study, the antibiofilm activity of QAL was tested in combination with tobramycin, an antibiotic commonly used for the therapy of infections sustained by P. aeruginosa [ 73 , 74 ]. Interestingly, QAL and tobramycin at concentrations below their MIC values markedly inhibited (90%) the biofilm formation of all P. aeruginosa strains tested.…”

Alginate oligosaccharides enhance diffusion and activity of colistin in a mucin-rich environment

“…Inhaled antimicrobials such as colistin, tobramycin and aztreonam lysine are the most commonly used antibiotics for the treatment of chronic P. aeruginosa infection in CF patients 45 . Inhalation therapy offers many advantages over systemically administered drugs, as high drug concentrations can be delivered directly to the airways, thereby improving efficacy and minimising systemic absorption and toxicity.…”

Nebulisation Therapy in Patients with Cystic Fibrosis—Consensus of the Polish Cystic Fibrosis Society

“…They can be used in cooperating patients with a very good motivation. Patients who are weakly motivated or who cannot cooperate yet, such as preschool children, are better advised cycles of antibiotics from different groups are increasingly recommended as a strategy to improve treatment outcomes, especially in patients with advanced lung disease [20]. In Poland, the limited access to inhaled antibiotics is a huge problem: only the preparation of colistin (Colistin TZF) is reimbursed, while tobramycin is available as part of a drug program, that excludes colistin interchangeability.…”