Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens

Abstract

Clinical trials have demonstrated the benefits of ibuprofen therapy in cystic fibrosis (CF) patients, an effect that is currently attributed to ibuprofen's anti-inflammatory properties. Yet, a few previous reports demonstrated an antimicrobial activity of ibuprofen as well, although none investigated its direct effects on the pathogens found in the CF lung, which is the focus of this work. Determination of ibuprofen's in vitro antimicrobial activity against Pseudomonas aeruginosa and Burkholderia species strains through measurements of the endpoint number of CFU and growth kinetics showed that ibuprofen reduced the growth rate and bacterial burden of the tested strains in a dose-dependent fashion. In an in vitro Pseudomonas biofilm model, a reduction in the rate of biomass accumulation over 8 h of growth with ibuprofen treatment was observed. Next, an acute Pseudomonas pneumonia model was used to test this antimicrobial activity after the oral delivery of ibuprofen. Following intranasal inoculation, ibuprofen-treated mice exhibited lower CFU counts and improved survival compared with the control animals. Preliminary biodistribution studies performed after the delivery of ibuprofen to mice by aerosol demonstrated a rapid accumulation of ibuprofen in serum and minimum retention in lung tissue and bronchoalveolar lavage fluid. Therefore, ibuprofen-encapsulated polymeric nanoparticles (Ibu-NPs) were formulated to improve the pharmacokinetic profile. Ibu-NPs formulated for aerosol delivery inhibited the growth of P. aeruginosa in vitro and may provide a convenient dosing method. These results provide an additional explanation for the previously observed therapeutic effects of ibuprofen in CF patients and further strengthen the argument for its use by these patients.

Ibuprofen Safety at the Golden Anniversary: Are all NSAIDs the Same? A Narrative Review

“…Thus, cystic fibrosis sets up a vicious cycle of infection, airway inflammation, and airway obstruction. Ibuprofen along with other NSAIDs and inhaled corticosteroids is sometimes used to help address the inflammation [107,108]. A recent study proposed that part of ibuprofen's effectiveness in this setting occurs because ibuprofen has an antimicrobial effect against Pseudomonas aeruginosa and Burkholderia bacteria associated with cystic fibrosis [108].…”

“…Ibuprofen along with other NSAIDs and inhaled corticosteroids is sometimes used to help address the inflammation [107,108]. A recent study proposed that part of ibuprofen's effectiveness in this setting occurs because ibuprofen has an antimicrobial effect against Pseudomonas aeruginosa and Burkholderia bacteria associated with cystic fibrosis [108]. Ibuprofen reduced the growth rate and bacterial burden of these bacteria in a dose-dependent fashion in an acute pseudomonas pneumonia mouse model [108].…”

“…A recent study proposed that part of ibuprofen's effectiveness in this setting occurs because ibuprofen has an antimicrobial effect against Pseudomonas aeruginosa and Burkholderia bacteria associated with cystic fibrosis [108]. Ibuprofen reduced the growth rate and bacterial burden of these bacteria in a dose-dependent fashion in an acute pseudomonas pneumonia mouse model [108]. A long-term clinical trial has found that ibuprofen may slow the progression of cystic fibrosis lung disease in children with ibuprofen-treated patients experiencing a 40% slower rate of decline compared with placebo (p = 0.02) [109].…”

Is Non-Steroidal Anti-Inflammatory Therapy Non-Inferior to Antibiotic Therapy in Uncomplicated Urinary Tract Infections: a Systematic Review

“…17 Furthermore, though evidence is mixed, NSAIDs may also have direct antimicrobial properties. [18][19][20][21] Within this context, Bleidorn and colleagues demonstrated in a 2010 randomized pilot study that NSAIDs were non-inferior for improving symptoms as well as preventing relapse and non-serious adverse events when compared with antibiotics for uncomplicated UTI. 22 Conversely, in 2015, Gágyor and colleagues found treatment with NSAIDs to be less effective compared with treatment with antibiotics for symptom relief and to result in more cases of pyelonephritis.…”

Repurposing bioactive compounds for treating multidrug-resistant pathogens

“…Antimicrobials have recently shown several interesting examples of this approach. For example, ibuprofen was shown to have antimicrobial properties and to elicit a therapeutic effect in cystic fibrosis patients [9,10]. Additionally, entecapone, a medication for Parkinson's disease, inhibited mycobacterial growth [11].…”