Abstract
Pulmonary exacerbations in adults with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (Psae) infection are usually treated with dual intravenous antibiotics for 14 days, despite the lack of evidence for best practice. Intravenous antibiotics are commonly associated with various systemic adverse effects, including renal failure and ototoxicity. Inhaled antibiotics are less likely to cause systematic adverse effects, yet can achieve airway concentrations well above conventional minimum inhibitory concentrations. Typically one inhaled antibiotic is used at a time, but dual inhaled antibiotics (i.e. concomitant use of two different inhaled antibiotics) may have synergistic effect and achieve better results in the treatment of exacerbations. We presented anecdotal evidence for the use of dual inhaled antibiotics as an acute treatment for exacerbations, in the form of a case report. A female in her early thirties with CF and chronic Psae infection improved her FEV1 by 5% and 2% with two courses of dual inhaled antibiotics to treat exacerbations in 2016. In contrast, her FEV1 changed by 2%, –2%, 0% and 2%, respectively, with four courses of dual intravenous antibiotics in 2016. Baseline FEV1 was similar prior to all six courses of treatments. The greater FEV1 improvements with dual inhaled antibiotics compared to dual intravenous antibiotics suggest the potential role of using dual inhaled antibiotics to treat exacerbations among adults with CF and chronic Psae infection, especially since a greater choice of inhaled anti-pseudomonal antibiotics is now available. A previous study in 1985 has looked at the concomitant administration of inhaled tobramycin and carbenicillin, by reconstituting antibiotics designed for parenteral administration. To our knowledge, this is the first literature to describe the concomitant use of two different antibiotics specifically developed for delivery via the inhaled route.
Highlights
Cystic fibrosis (CF) is a genetic condition whereby ~80% of mortalities are primarily due to lung disease[1]
As recommended by Dr Liou, we have: 1. clarified which treatment courses were for acute exacerbation - the 1st dual nebulised antibiotics course was for acute exacerbation and the 3rd intravenous antibiotics course was for acute exacerbation (4% absolute decline in FEV1 from previous there was no clear symptoms) 2. iterated the sentence in 2nd paragraph of “case report” to clarify the more intensive treatment during the follow-up year 3. provided more detailed results for sputum cultures 4. provided in generic name with first use of trademarked names for nebulised antibiotics, and only using generic name for intravenous antibiotics
There is a lack of evidence for best practice in treating exacerbations among adults with CF and chronic Pseudomonas aeruginosa (Psae) infection[4], two weeks of dual intravenous antibiotics are generally used for synergistic effect[4,5]
Summary
Clarified that the subject was using nebulised dornase alfa throughout all treatment courses 4. Provided objective adherence (I-neb data) during the dual nebulised antibiotics courses. As recommended by Drs Frost and Nazareth, we have: 1. Described organisms isolated from her sputum in the prior-year, follow-up year and subsequent year (this was recommended by Dr Liou) 4. Clarified which treatment courses were for acute exacerbation - the 1st dual nebulised antibiotics course was for acute exacerbation (subject was symptomatic %FEV1 was relatively stable) and the 3rd intravenous antibiotics course was for acute exacerbation (4% absolute decline in FEV1 from previous there was no clear symptoms) 2. Provided in generic name with first use of trademarked names for nebulised antibiotics, and only using generic name for intravenous antibiotics. We have explained in our response to Dr Liou’s comments that we felt adequate history has been provided (especially in terms of age and genotype), and that we have already provided a gold-standard adherence measure in the form of adherence data captured using I-neb (a data logging nebuliser)
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