Rationales

Treatment

Recommendations 1.1.2 to 1.1.5

Why the committee made the recommendations

The committee agreed, based on their experience, that people with an acute exacerbation of bronchiectasis presenting with worsening local symptoms (such as cough, increased sputum volume, change of sputum viscosity or increased sputum purulence) with or without increased wheeze, breathlessness, haemoptysis, fever or pleurisy, should receive an antibiotic. Choice should take account of the severity of their symptoms, their previous exacerbation and hospital admission history, their risk of developing complications, and previous sputum culture and susceptibility results.

The committee discussed the limited evidence base for antibiotics for treating an acute exacerbation of bronchiectasis. No evidence was found comparing antibiotics with placebo from systematic reviews or randomised controlled trials from the search, which went back to 2006. However, the committee were aware of older, heterogeneous, head-to-head studies comparing different antibiotic regimens (which may not reflect current practice).

Based on experience, the committee agreed that although in the first instance, antibiotic treatment for an acute exacerbation may be empirical, a new sputum sample should be sent for culture to confirm susceptibility of the bacteria. The committee discussed that for empirical treatment, antibiotics should be chosen initially based on the most recent sputum culture and susceptibility results. People with bronchiectasis are likely to have previous sputum samples, and because pathogenic bacteria are reasonably static in this population, antibiotics that worked previously are a good starting point to treat new exacerbations. However, pathogenic bacteria can change and a new sputum sample should be sent for culture when people present with a new exacerbation of bronchiectasis, and this new susceptibility data used to review antibiotic choice. The committee discussed the importance of all prescribers having access to microbiology results, with hospital managers ensuring that primary care teams have easy access to microbiology results.

Based on experience, the committee agreed that when results of sputum cultures are available, if they suggest the bacteria are not susceptible, the person should be contacted to assess symptoms. However, the antibiotic should only be changed according to susceptibility results if symptoms are not already improving. In line with good antimicrobial stewardship, narrow-spectrum antibiotics should be used wherever possible.

The committee agreed that when an antibiotic is given, people should be advised about possible adverse effects and also be given safety netting advice.

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Reassessment

Recommendation 1.1.6

Why the committee made the recommendation

Based on experience, the committee agreed that, for safety netting, reassessment was needed if symptoms of the acute exacerbation worsen rapidly or significantly at any time.

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Referral and seeking specialist advice

Recommendations 1.1.7 and 1.1.8

Why the committee made the recommendations

Based on experience, the committee agreed that, for safety netting, people with an acute exacerbation of bronchiectasis should be referred to hospital if they have any symptoms or signs suggesting a more serious illness or condition (for example, cardiorespiratory failure or suspected sepsis).

The committee discussed that some people who are severely ill or have resistant bacteria (particularly Pseudomonas aeruginosa) may need intravenous antibiotics, particularly if their symptoms are not responding to several courses of oral antibiotics for the same episode, or if several sputum samples show resistance to oral antibiotics. The committee discussed that specialist advice should be sought for people needing intravenous antibiotics, to discuss local options for giving intravenous antibiotics at home or in the community, rather than in hospital, if this is appropriate for the person.

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Choice of antibiotic for treating an acute exacerbation of bronchiectasis

Recommendations 1.2.1 to 1.2.3 and tables 1 and 2

Why the committee made the recommendations

Antibiotic choice

Very limited evidence was identified to guide the choice of antibiotic for treating an acute exacerbation of bronchiectasis. Based on experience, common pathogens in acute exacerbations, the susceptibility of these to various classes of antibiotics, the risks of resistance and good antimicrobial stewardship, the committee agreed the following antibiotic choices for empirical treatment in the absence of current susceptibility data. Choice should be guided by the most recent sputum culture and susceptibilities where possible. Several oral and intravenous antibiotics were recommended to enable antibiotics to be selected based on the severity of illness and previous antibiotic use.

First-choice oral antibiotics for empirical treatment are:

  • amoxicillin (a penicillin), which has good activity against common pathogens, such as Streptococcus pneumoniae and Haemophilus influenzae

  • clarithromycin (a macrolide)

  • doxycycline (a tetracycline; adults and young people over 12 years only).

Alternative choice oral antibiotics for empirical treatment for people who are at higher risk of treatment failure (which may include people who have had repeated courses of antibiotics, a previous sputum culture with resistant or atypical bacteria, or people at higher risk of developing complications) are:

  • co-amoxiclav, a broad-spectrum antibiotic which combines a penicillin with a beta-lactamase inhibitor, making it active against beta-lactamase-producing bacteria that are resistant to amoxicillin alone or

  • a fluoroquinolone: levofloxacin in adults or ciprofloxacin in children (only on specialist advice because fluoroquinolones are generally not recommended in children or young people who are growing), which have good activity against atypical bacteria, particularly Pseudomonas aeruginosa.

The committee was aware of the European Medicines Agency's Pharmacovigilance Risk Assessment Committee recommendation to restrict the use of fluoroquinolone antibiotics following a review of disabling and potentially long-lasting side effects mainly involving muscles, tendons and bones and the nervous system (press release October 2018). This includes a recommendation to not use them for mild or moderately severe infections unless other antibiotics cannot be used. The committee discussed that fluoroquinolones are appropriate as an alternative option for people who may be at a higher risk of treatment failure. However, the committee was keen to point out that fluoroquinolone safety concerns should be taken into account on an individual patient basis.

First-choice intravenous antibiotics for empirical treatment in people who are unable to take oral antibiotics or are severely unwell are:

  • co-amoxiclav (a penicillin with a beta-lactamase inhibitor)

  • piperacillin with tazobactam (an antipseudomonal penicillin with a beta-lactamase inhibitor)

  • levofloxacin (in adults) or ciprofloxacin (in children [on specialist advice only]), which are fluoroquinolones.

When current susceptibility data are available, antibiotics should be chosen and modified accordingly, consulting local microbiologists as needed.

The committee discussed evidence from a randomised controlled trial, which showed that adding nebulised tobramycin to oral ciprofloxacin did not improve the resolution of exacerbation symptoms, and increased wheeze.

Antibiotic course length

Very limited evidence was identified to guide the duration of antibiotics for treating an acute exacerbation of bronchiectasis. The 1 randomised controlled trial identified, which compared a nebulised antibiotic plus an oral antibiotic with an oral antibiotic alone, used a 14‑day course, which is current practice.

Based on experience, the committee agreed that the shortest course that is likely to be effective should be prescribed to reduce the risk of antimicrobial resistance and minimise the risk of adverse effects.

The committee agreed that a course of 7 to 14 days was required to treat an acute exacerbation, based on an assessment of the person's severity of bronchiectasis, their exacerbation history, the severity of their exacerbation symptoms, previous culture and susceptibility results, and response to treatment.

Oral antibiotics should be used first line where possible, in line with the NICE guideline on antimicrobial stewardship.

The committee agreed that the use of intravenous antibiotics should be reviewed by 48 hours (taking into account the person's response to treatment and susceptibility results from sputum culture) and switched to oral treatment where possible. This aligns with the NICE guideline on antimicrobial stewardship and Public Health England's Start smart – then focus.

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Preventing acute exacerbations of bronchiectasis (non-cystic fibrosis) and choice of antibiotic

Recommendations 1.3.1 to 1.3.3

Why the committee made the recommendations

Prophylactic antibiotics

The committee discussed the evidence for prophylactic antibiotics. Overall, antibiotics reduced exacerbation rates, hospitalisations and the number of people with an exacerbation. However, there was a significant increase in antibiotic resistance and adverse effects.

Most of the studies were in populations who had experienced multiple exacerbations in the previous year, and the committee thought the findings could not be generalised to everyone with bronchiectasis.

Based on evidence and experience, the committee agreed that people should not routinely be offered antibiotic prophylaxis to prevent acute exacerbations, because of the balance of risks and benefits in the overall population.

For people with repeated exacerbations, where the benefits of prophylaxis may outweigh the risks, specialist advice should be sought on various management options, which may include a trial of antibiotic prophylaxis (with oral or inhaled antibiotics).

The committee noted it was difficult to give a precise definition of 'repeated exacerbations' and clinical judgement would be needed to define this on an individualised patient basis.

The committee agreed that a trial of antibiotic prophylaxis should only be started in people with repeated acute exacerbations on the advice of a specialist, because it is important to consider antibiotic prophylaxis alongside other management options. Shared decision-making is important for taking into account the risks and benefits of prophylaxis on an individualised patient basis. This includes discussing the potential benefits of antibiotics for reducing exacerbations, but also the harms of long-term antibiotics. There is an increased risk of resistance with long-term antibiotics, which impacts at both a population and an individual level, and people should be advised that this can mean fewer antibiotics may work for their exacerbations in the future. People should also be advised about possible adverse effects. With macrolides, diarrhoea is common but there are also less common cardiac events, hearing loss and tinnitus, and the potential to interact with other medicines. Bronchospasm is a possible adverse effect with inhaled antibiotics and a challenge test is needed. The committee discussed that people being considered for antibiotic prophylaxis would also need to return for regular review.

The committee discussed that most evidence for prophylactic antibiotics was for oral macrolide antibiotics in adults, where they reduced exacerbation rates and the number of people with an exacerbation. However, they also increased antibiotic resistance and adverse effects. The limited evidence in children and young people found prophylactic oral macrolide antibiotics did not significantly reduce exacerbations but increased antimicrobial resistance.

The evidence for nebulised or inhaled antibiotics was particularly limited, and not all products studied are available in the UK. As a class, prophylaxis with nebulised or inhaled antibiotics did not significantly reduce exacerbations in adults. In 1 trial of nebulised colistimethate sodium in people with chronic Pseudomonas aeruginosa infection, exacerbations were significantly reduced in an adherent population, but not in the intention-to-treat population, which was the primary end point. In another trial of nebulised tobramycin, a non-significant increase in exacerbations, and adverse events such as dyspnoea, chest pain and wheeze were seen.

The committee were unable to make specific recommendations on the choice of antibiotic for prophylaxis, because this will be an individualised decision based on the clinical needs of the person, their preferences and advice from a specialist.

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See the full evidence review for a summary of the evidence and more information.

  • Public Health England
  • National Institute for Health and Care Excellence (NICE)