Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis
Sherie Smith1, Nicola J Rowbotham, Edward Charbek
1Division of Child Health, Obstetrics & Gynaecology, School of Medicine, The University of Nottingham, 1701 E Floor, East Block Queens Medical Centre, Nottingham, NG7 2UH, UK.
Background:
Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review.
Objectives:
To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival.
Search Methods:
We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 03 October 2018.We searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 09 October 2018.
Selection Criteria:
Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks.
Data Collection And Analysis:
Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the quality of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information.
Main Results:
Four trials with 167 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and two trials (90 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials, but for all trials we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis.Inhaled antibiotics alone versus intravenous antibiotics aloneOnly one trial (n = 18) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-quality of evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-quality evidence). With regards to our secondary outcomes, one trial (n = 18) reported no difference in the need for additional antibiotics and the second trial (n = 59) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-quality evidence). The single trial (n = 18) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-quality evidence).Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics aloneNeither trial reported on quality of life or time off work or school. Both trials measured lung function, but found no difference between groups in forced expiratory volume in one second (one trial, n = 28, very low-quality evidence) or vital capacity (one trial, n = 62). Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (n = 28) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events (very low-quality evidence) and one trial (n = 62) reported no difference in the emergence of antibiotic-resistant organisms (very low-quality evidence).
Authors' Conclusions:
There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.
Insights
Limited evidence suggests inhaled antibiotics may not significantly improve outcomes for cystic fibrosis pulmonary exacerbations. Further research is needed to determine if inhaled tobramycin is a viable alternative to intravenous treatments.
Area of Science:
- Pulmonary Medicine
- Genetics
- Pharmacology
Background:
- Cystic fibrosis (CF) is a genetic disorder causing abnormal mucus buildup in the lungs, leading to persistent infections and pulmonary exacerbations.
- Antibiotics, including inhaled formulations, are crucial for managing CF pulmonary exacerbations, offering an alternative to intravenous antibiotics with potentially fewer adverse effects.
Purpose of the Study:
- To evaluate the effectiveness of inhaled antibiotics in treating pulmonary exacerbations in individuals with cystic fibrosis.
- To determine if inhaled antibiotic treatment improves quality of life, reduces school/work absence, and enhances long-term survival in CF patients.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing inhaled antibiotics to placebo, standard care, or other inhaled antibiotics for CF pulmonary exacerbations.
- Searched multiple clinical trial registries and databases up to October 2018.
- Four trials involving 167 participants were included, with varying designs and limited data availability.
Main Results:
- Limited, very low-quality evidence from two trials comparing inhaled antibiotics alone versus intravenous antibiotics alone showed no significant differences in lung function or time to next exacerbation.
- Two trials comparing combined inhaled and intravenous antibiotics to intravenous antibiotics alone also found no significant differences in lung function, hospital admissions, or adverse events.
- Trials were heterogeneous, had a high risk of bias due to lack of blinding, and were often underpowered, limiting definitive conclusions.
Conclusions:
- There is insufficient high-quality evidence to establish the effectiveness of inhaled antibiotics for treating pulmonary exacerbations in cystic fibrosis.
- The included trials lacked the statistical power to demonstrate superiority of any treatment regimen.
- Further well-designed, adequately powered research is necessary to ascertain if inhaled antibiotics, such as tobramycin, can serve as effective alternatives to intravenous therapies for CF pulmonary exacerbations.
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