Description of the condition

Bronchiectasis is characterised by abnormal dilation of the airways that is associated with a pathological mechanism of progressive airway destruction, due to the 'vicious cycle' of recurrent bacterial infection, inflammatory mediator release, airway damage and subsequent further infection (Cole 1986). The airways show chronic inflammation with various features, including loss of ciliated epithelium and mucous gland hypertrophy. Bacterial colonisation is facilitated by this loss of an integral epithelial structure (host defence) which, in turn, triggers further immune responses and a continuation of the inflammatory process. An understanding of this cycle is central to the management of bronchiectasis as strategies to arrest both inflammatory and bacterial components are required to limit the progression of lung injury. Typically microbiology for bronchiectasis patients includes Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and, importantly, Pseudomonas aeruginosa, though the microbiological profile differs between adults and children with Pseudomonas more common in adults and prevalent in only 0% to 6% of children. Pseudomonas colonisation often occurs later in the natural progression of the condition and may infer a worse prognosis in terms of symptoms, exacerbations and loss of lung function (Evans 1996). In severe cases, the cycle of lung infection may lead to repeated hospitalisation, chronic respiratory failure and death.

Most adult cases of bronchiectasis are either idiopathic or due to a previous severe lung infection. However, treatable causes, such as immune‐deficiency, allergic bronchopulmonary aspergillosis, mycobacterial infection and recurrent aspiration may be identified in a minority of cases (Pasteur 2010; Goeminne 2012; Wilson 2013). One study found a proportion of cases were associated with chronic obstructive pulmonary disease (COPD) and connective tissue diseases (Loni 2015). Underlying causes can be determined in up to 70% of paediatric cases (Eastham 2004; Twiss 2005). Diagnosis is based on a combination of clinical symptoms and high‐resolution computerised tomography (HRCT) that show one or more abnormally dilated bronchi (Chang 2010; Pasteur 2010). Symptoms may include chronic productive cough, wheeze and breathlessness, together with recurrent lower respiratory tract infections. Colonisation with P. aeruginosa and frequent exacerbations are associated with accelerated decline in lung function (Evans 1996; Martínez García 2007), and, along with impaired exercise capacity and respiratory symptoms, reduced quality of life and hospitalisations (Wilson 1997; Finch 2015).

Management of bronchiectasis requires careful attention to sputum clearance, bronchodilator therapy, and the prescription of antibiotics (Welsh 2015). In the short term, the main aim is to reduce microbial load in order to reduce the severity and frequency of exacerbations, thereby ameliorating symptoms and improving quality of life (Pasteur 2010), with the longer‐term aim of breaking the infection cycle, slowing the decline in lung function and reducing mortality rates. Antibiotics have traditionally been reserved for the treatment of acute infection/exacerbation although there is possibly a role for prophylactic strategies in some cases. Latterly the use of macrolides has attracted further interest and trials have explored their prescription in bronchiectasis patients (Wu 2014).

Global prevalence estimates are unclear because of variable diagnostic strategies (Weycker 2005), and higher prevalence rates in low and middle income countries (Habesoglu 2011). Mortality rates in England and Wales rose by 3% per year between 2001 to 2007 (Roberts 2010), and hospitalisations also increased by 3% per year over a nine‐year period in the USA (Seitz 2010). Higher prevalence rates were associated with people over 60 years of age and women, and varied by ethnicity (Chang 2003; Seitz 2012). Recent data from a UK study suggests that incidence and prevalence may be higher than previously estimated (Quint 2016). Over a nine‐year period to 2013, point prevalence rates per 100,000 rose from 350.5 to 566.1 in women and from 301.2 to 485.5 in men. This reflects an increase of more than 60% with almost 263,000 adults living with bronchiectasis in 2013. Similarly, the incidence rates per 100,000 person‐years rose from 21.2 to 35.2 in women and from 18.2 to 26.9 in men. Representing an approximate increase in new cases of 63% to over 15,000 in 2013. Bronchiectasis is also associated with higher age‐adjusted mortality rates, with estimates 2.26 times higher in women and 2.14 times higher in men compared to the general population (Quint 2016). The disease has a significant impact on paediatric populations where quality of life is worse for younger children and those with a more frequent annual exacerbation rate (Kapur 2012). Global prevalence estimates are variable, ranging from conservative estimates of 17.2 in the North‐East of England (Eastham 2004), to 33.5 in New Zealand (Twiss 2005), per 100,000 children under 15 years. Rates may be higher in children from indigenous populations, with estimates of 1 per 625 (160 per 100,000) in children from the pacific islands (Twiss 2005), 15 per 1000 (1500 per 100,000) in native central Australian Aborginal children, and 16 per 1000 (1600 per 100,000) in native Alaksan children (Singleton 2000; Chang 2002).

The economic burden of bronchiectasis may be considerable but little data is available. Data collected in 2001 in the USA reported an additional 2.0 days in hospital, 6.1 more outpatient encounters and 27.2 more days of antibiotic therapy associated with bronchiectasis (Weycker 2005). Estimates of the overall additional annual costs of bronchiectasis range from USD 5681 to USD 7827, based on data collected between 2001 and 2009 (Weycker 2005; Seitz 2010; Joish 2013).

Description of the intervention

Bronchiectasis is characterised by daily coughing, sputum expectoration and recurrent respiratory infection. Serial infections often culminate in bacterial colonisation with dilatation and inflammation of the airways. Whilst abnormalities may be pan‐lobar (i.e. throughout both lungs), infection may be limited to a single lung lobe or manifest in a patchy distribution. Antibiotics are used to reduce bacterial burden, to tackle the cycle of infection and tissue damage (Cole 1984; Pasteur 2010). They may be administered short‐term (less than four weeks) to treat acute exacerbations or for longer (≥ 4 weeks). Longer durations of antibiotics are used for pathogen eradication, suppression of bacterial load or for anti‐inflammatory properties (e.g. macrolides). Several routes of administration are available including: oral, inhaled and parenteral routes, with analysis of sputum bacteriology informing the specific choice of antibiotic. Prescribing is also informed by clinical context as well as bacteriology and sputum purulence is considered a reliable indicator of the need for treatment (Hill 1988). Antibiotics may therefore be prescribed before the results of sputum bacteriology are obtained. Antibiotics are a frontline therapy for the management of bacterial load in bronchiectasis but their use is tempered with the need for considered use in the face of adverse effects and increasing concerns over antibiotic resistance (Pasteur 2010).

How the intervention might work

A range of antibiotic strategies have been used to reduce bacterial load and re‐infection rates in people with bronchiectasis, including short‐term prescriptions for acute exacerbations and longer‐term prophylactic use in patients with frequent exacerbations where chronic sputum purulence is a common feature (Evans 2003; Chalmers 2012). Longer‐term use of antibiotics is not currently recommended as part of routine treatment (Valery 2012; Wu 2014), but may be considered for patients with frequent exacerbations (three or more per year requiring antibiotic therapy) (Pasteur 2010). Antibiotic choice is usually guided by sputum microbiology and patterns of local antibiotic resistance but treatment is often started empirically with a broad spectrum oral or intravenous antibiotic until the specific pathogen has been isolated. If there is more than one positive culture an antibiotic is selected to cover both. However, dual therapy is likely where monotherapy will not suffice, such as with Pseudomonas spp, a common pathogen in bronchiectasis. Macrolide antibiotics may additionally be prescribed for their potential anti‐inflammatory properties as well as antibacterial effects.

Why it is important to do this review

Evidence for the effectiveness of a range of treatment strategies in bronchiectasis is limited by the number and quality of clinical trials, including those on antibiotics, and the need for evidence on head‐to‐head comparisons of antibiotics have been highlighted as a key priority (Welsh 2015). The comparative cost‐effectiveness of within‐class antibiotics, e.g. from different manufacturers, is unclear but this type of evidence could be used to inform choice of antibiotic, particularly in developing countries where use of cheaper antibiotics may be more prevalent compared to developed countries.

Therefore this Cochrane Review will include studies that directly compare the effectiveness of two or more antibiotics, as well as consider issues relating to duration of treatment and mode of delivery. We will endeavour to draw together existing evidence comparing their effectiveness for non‐cystic fibrosis bronchiectasis against key outcomes identified by Welsh 2015. We are conducting this as a Cochrane Review employing established methodology in accordance with the recent evaluation of these standards versus alternative approaches (Page 2016). This Cochrane Review is being conducted alongside four other closely‐related reviews: Macrolide antibiotics for non‐cystic fibrosis bronchiectasis (Kelly 2016) ;Dual antibiotics for non‐cystic fibrosis bronchiectasis (Felix 2017a); Oral versus inhaled antibiotics for non‐cystic fibrosis bronchiectasis (Spencer 2017); and Continuous versus intermittent antibiotics for non‐cystic bronchiectasis (Felix 2017b). .