How do different antibiotics compare in terms of safety and treatment effectiveness for people with bronchiectasis?


Background
Bronchiectasis is defined as abnormal widening of the airways in the lungs. It is usually caused by repeated bacterial chest infections, which damage the airways. Antibiotics are the main option for treating these infections and are used to prevent repeated infections over the longer term. However, use of antibiotics must be weighed against potential side effects and concerns over the development of bacterial resistance to treatment with antibiotics that reduces their effectiveness. Only a small number of studies have focused on antibiotics for people with bronchiectasis. Further clarity about how different antibiotics compare with one another is urgently needed.

Study characteristics
In April 2018, we looked for studies including adults or children with bronchiectasis that randomly allocated participants to receive one antibiotic or another by the same method of administration. We found only four studies, and they were very small. In total, they included 138 participants. This small sample makes it very difficult to draw clear conclusions.

Key results
Four randomised trials were eligible for inclusion in this systematic review. None of the included studies reported information on flare-ups (exacerbations). Included studies reported no deaths and no serious adverse events. Treatment failures were fewer with fluoroquinolone antibiotics than with amoxicillin antibiotics.

Quality of the evidence
Reviewers considered the quality of the evidence provided by the four small included studies to be low or very low.

Key message

Fluoroquinolone antibiotics may be more successful than amoxicillin antibiotics in treating exacerbations, but this finding is based on low-quality evidence. More evidence from high-quality clinical trials of short-term and long-term treatment with antibiotics is needed if clear conclusions are to be reached on the benefits of one antibiotic over another for people with bronchiectasis.

Authors' conclusions: 

Limited low-quality evidence favours short-term oral fluoroquinolones over beta-lactam antibiotics for patients hospitalised with exacerbations. Very low-quality evidence suggests no benefit from inhaled aminoglycosides verus polymyxins. RCTs have presented no evidence comparing other modes of delivery for each of these comparisons, and no RCTs have included children. Overall, current evidence from a limited number of head-to-head trials in adults or children with bronchiectasis is insufficient to guide the selection of antibiotics for short-term or long-term therapy. More research on this topic is needed.

Read the full abstract...
Background: 

The diagnosis of bronchiectasis is defined by abnormal dilation of the airways related to a pathological mechanism of progressive airway destruction that is due to a 'vicious cycle' of recurrent bacterial infection, inflammatory mediator release, airway damage, and subsequent further infection. Antibiotics are the main treatment option for reducing bacterial burden in people with exacerbations of bronchiectasis and for longer-term eradication, but their use is tempered against potential adverse effects and concerns regarding antibiotic resistance. The comparative effectiveness, cost-effectiveness, and safety of different antibiotics have been highlighted as important issues, but currently little evidence is available to help resolve uncertainty on these questions.

Objectives: 

To evaluate the comparative effects of different antibiotics in the treatment of adults and children with bronchiectasis.

Search strategy: 

We identified randomised controlled trials (RCTs) through searches of the Cochrane Airways Group Register of trials and online trials registries, run 30 April 2018. We augmented these with searches of the reference lists of published studies.

Selection criteria: 

We included RCTs reported as full-text articles, those published as abstracts only, and unpublished data. We included adults and children (younger than 18 years) with a diagnosis of bronchiectasis by bronchography or high-resolution computed tomography who reported daily signs and symptoms, such as cough, sputum production, or haemoptysis, and those with recurrent episodes of chest infection; we included studies that compared one antibiotic versus another when they were administered by the same delivery method.

Data collection and analysis: 

Two review authors independently assessed trial selection, data extraction, and risk of bias. We assessed overall quality of the evidence using GRADE criteria. We made efforts to collect missing data from trial authors. We have presented results with their 95% confidence intervals (CIs) as mean differences (MDs) or odds ratios (ORs).

Main results: 

Four randomised trials were eligible for inclusion in this systematic review - two studies with 83 adults comparing fluoroquinolones with β-lactams and two studies with 55 adults comparing aminoglycosides with polymyxins.

None of the included studies reported information on exacerbations - one of our primary outcomes. Included studies reported no serious adverse events - another of our primary outcomes - and no deaths. We graded this evidence as low or very low quality. Included studies did not report quality of life. Comparison between fluoroquinolones and β-lactams (amoxicillin) showed fewer treatment failures in the fluoroquinolone group than in the amoxicillin group (OR 0.07, 95% CI 0.01 to 0.32; low-quality evidence) after 7 to 10 days of therapy. Researchers reported that Pseudomonas aeruginosa infection was eradicated in more participants treated with fluoroquinolones (Peto OR 20.09, 95% CI 2.83 to 142.59; low-quality evidence) but provided no evidence of differences in the numbers of participants showing improvement in sputum purulence (OR 2.35, 95% CI 0.96 to 5.72; very low-quality evidence). Study authors presented no evidence of benefit in relation to forced expiratory volume in one second (FEV₁). The two studies that compared polymyxins versus aminoglycosides described no clear differences between groups in the proportion of participants with P aeruginosa eradication (OR 1.40. 95% CI 0.36 to 5.35; very low-quality evidence) or improvement in sputum purulence (OR 0.16, 95% CI 0.01 to 3.85; very low-quality evidence). The evidence for changes in FEV₁ was inconclusive. Two of three trials reported adverse events but did not report the proportion of participants experiencing one or more adverse events, so we were unable to interpret the information.

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