Colistimethate sodium for the treatment of chronic pulmonary infection in cystic fibrosis: an evidence-based review of its place in therapy

Abstract

Chronic bacterial respiratory-tract infections are a major driving force in the pathogenesis of cystic fibrosis (CF) lung disease and promote chronic lung-function decline, destruction, and progression to respiratory failure at a premature age. Gram-negative bacteria colonizing the airways in CF are a major problem in CF therapy due to their tendency to develop a high degree of resistance to antibiotic agents over time. Pseudomonas aeruginosa is the dominating bacterial strain infecting the CF lung from early childhood on, and multiresistant strains frequently develop after years of therapy. Colistin has been used for treating pulmonary bacterial infections in CF for decades due to its very good Gram-negative activity. However, drawbacks include concerns regarding toxicity when being applied systemically, and the lack of approval for application by inhalation in the USA for many years. Other antibiotic substances for systemic use are available with good to excellent Gram-negative and anti-Pseudomonas activity, while there are only three substances approved for inhalation use in the treatment of chronic pulmonary infection with proven benefit in CF. The emergence of multiresistant strains leaving nearly no antibiotic substance as a treatment option, the limited number of antibiotics with high activity against P. aeruginosa, the concerns about increasing the risk of antibiotic resistance by continuous antibiotic therapy, the development of new drug formulations and drug-delivery devices, and, finally, the differing treatment strategies used in CF centers call for defining the place of this “old” drug, colistimethate, in today’s CF therapy. This article reviews the available evidence to reflect on the place of colistimethate sodium in the therapy of chronic pulmonary infection in CF.

Nitric oxide diffusion through cystic fibrosis-relevant media and lung tissue

“…1,8,9 As such, severe chronic infections persist in the lungs of CF patients, requiring the constant administration of antibiotics (e.g., colistin and tobramycin) to mitigate infections and prolong the lives of those afflicted with CF. 3,10,11 The continuous administration of antibiotics required to combat these chronic infections has led to the rapid rise of multi-drug resistant (MDR) bacteria in the CF community, necessitating the development of novel therapeutics. 12,13 Nitric oxide (NO), an endogenously produced free radical, is capable of inducing both oxidative and nitrosative stress (e.g., damaging membrane proteins and DNA, lipid peroxidation) to eradicate bacteria.…”

Accurate reporting of adherence to inhaled therapies in adults with cystic fibrosis: methods to calculate normative adherence

“… 38 There is evidence that the decline can be reduced by long-term inhaled antibiotics. 7 , 39 , 40 Colistimethate sodium and tobramycin are the two most commonly used antibiotics to suppress chronic Pseudomonas , while aztreonam lysine is a new treatment available since 2012. 41 All the main CF guidelines recommend the use of long-term inhaled antibiotics if a person with CF is chronically colonized with Pseudomonas .…”

lncRNAPCAT29 inhibits pulmonary fibrosis via the TGF‑β1‑regulated RASAL1/ERK1/2 signal pathway

“…A systematic review and meta-analysis demonstrated the association between the severity of breathing disorders, and the aggregation of extracellular matrix components and inflammation-associated injury (4). A reported increase in the incidence and mortality rates of pulmonary fibrosis has been associated with the development of severe acute respiratory syndrome (5). Therefore, understanding the potential signaling mechanism underlying pulmonary fibrosis is essential to understand the progression of this disease.…”