Intermittent prophylactic antibiotics for bronchiectasis.

backgroundBronchiectasis is a common but under-diagnosed chronic disorder characterised by permanent dilation of the airways arising from a cycle of recurrent infection and inflammation. Symptoms including chronic, persistent cough and productive phlegm are a significant burden for people with bronchiectasis, and the main aim of treatment is to reduce exacerbation frequency and improve quality of life. Prophylactic antibiotic therapy aims to break this infection cycle and is recommended by clinical guidelines for adults with three or more exacerbations a year, based on limited evidence. It is important to weigh the evidence for bacterial suppression against the prevention of antibiotic resistance and further evidence is required on the safety and efficacy of different regimens of intermittently administered antibiotic treatments for people with bronchiectasis.

objectivesTo evaluate the safety and efficacy of intermittent prophylactic antibiotics in the treatment of adults and children with bronchiectasis. SEARCH

methodsWe identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted searches on 6 September 2021, with no restriction on language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of at least three months' duration comparing an intermittent regime of prophylactic antibiotics with placebo, usual care or an alternate intermittent regimen. Intermittent prophylactic administration was defined as repeated courses of antibiotics with on-treatment and off-treatment intervals of at least 14 days' duration. We included adults and children with a clinical diagnosis of bronchiectasis confirmed by high resolution computed tomography (HRCT), plain film chest radiograph, or bronchography and a documented history of recurrent chest infections. We excluded studies where participants received high dose antibiotics immediately prior to enrolment or those with a diagnosis of cystic fibrosis, allergic bronchopulmonary aspergillosis (ABPA), primary ciliary dyskinesia, hypogammaglobulinaemia, sarcoidosis, or a primary diagnosis of COPD. Our primary outcomes were exacerbation frequency and serious adverse events. We did not exclude studies on the basis of review outcomes. DATA COLLECTION AND ANALYSIS: We analysed dichotomous data as odds ratios (ORs) or relative risk (RRs) and continuous data as mean differences (MDs) or standardised mean differences (SMDs). We used standard methodological procedures expected by Cochrane. We conducted GRADE assessments for the following primary outcomes: exacerbation frequency; serious adverse events and secondary outcomes: antibiotic resistance; hospital admissions; health-related quality of life. MAIN

resultsWe included eight RCTs, with interventions ranging from 16 to 48 weeks, involving 2180 adults. All evaluated one of three types of antibiotics over two to six cycles of 28 days on/off treatment: aminoglycosides, ß-lactams or fluoroquinolones. Two studies also included 12 cycles of 14 days on/off treatment with fluoroquinolones. Participants had a mean age of 63.6 years, 65% were women and approximately 85% Caucasian. Baseline FEV AUTHORS'

conclusionsOverall, in adults who have frequent chest infections, long-term antibiotics given at 14-day on/off intervals slightly reduces the frequency of those infections and increases antibiotic resistance. Intermittent antibiotic regimens result in little to no difference in serious adverse events. The impact of intermittent antibiotic therapy on children with bronchiectasis is unknown due to an absence of evidence, and further research is needed to establish the potential risks and benefits.