Intervention and alternatives

Intervention and alternatives

Colistimethate sodium is a polymyxin antibiotic that is active against gram negative bacteria including Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. It is not absorbed when given orally.

Inhaled colistimethate sodium is licensed for treating pulmonary infections caused by P. aeruginosa in people with cystic fibrosis. The following preparations are available:

  • Colobreathe dry powder for inhalation using the Turbospin inhaler. Each capsule contains 1.6625 million international units, equivalent to 125 mg of colistimethate sodium. This preparation is licensed only for chronic pulmonary infections in people aged 6 years and older.

  • Colomycin injection powder for solution for inhalation using a nebuliser. Each vial contains 1 or 2 million international units of colistimethate sodium (dose equivalent not specified).

  • Promixin powder for nebuliser solution. Each vial contains 1 million international units, equivalent to 80 mg colistimethate sodium.

There are currently no licensed colistimethate products for the treatment of non-cystic fibrosis bronchiectasis. However, the manufacturer of Promixin, Profile Pharma, has indicated that it intends to apply for a UK marketing authorisation within 2–3 years for nebulised colistimethate sodium for treating chronic P. aeruginosa infection.

In clinical practice, colistimethate is reportedly used in a similar way for non-cystic fibrosis bronchiectasis caused by P. aeruginosa to how it is used in people with cystic fibrosis. The limitations of the evidence for this use are discussed in the evidence review section. NICE guidance on Colistimethate sodium and tobramycin dry powders for inhalation for treating pseudomonas lung infection in cystic fibrosis recommends colistimethate sodium dry powder for inhalation (Colobreathe) as an option for treating chronic pulmonary infection caused by P. aeruginosa in people with cystic fibrosis only if:

  • they would clinically benefit from continued colistimethate sodium but do not tolerate it in its nebulised form (Colomycin injection or Promixin) and thus tobramycin therapy would otherwise be considered and

  • the manufacturer provides colistimethate sodium dry powder for inhalation with the discount agreed as part of the patient access scheme to primary, secondary and tertiary care in the NHS.

When used for its licensed indication in adults and children older than 2 years, the recommended dose of nebulised colistimethate sodium is 1 to 2 million international units 2 to 3 times daily, depending on the preparation (Colomycin injection or Promixin). Colomycin may be used at a lower dose in children younger than 2 years. The recommended dose of colistimethate sodium dry powder for inhalation (Colobreathe) for adults and children older than 6 years is 1 capsule for inhalation twice daily using the Turbospin inhaler.

Condition

The lungs have a sophisticated defence mechanism to maintain sterility. However, if this is breached they become susceptible to infection, colonisation (the persistence of bacteria in the lower respiratory tract) can occur, and subsequent inflammation can cause airway damage and further impair the lungs' defences. The British Thoracic Society guideline for non-CF bronchiectasis defines bronchiectasis as persistent or recurrent bronchial sepsis related to irreversibly damaged and dilated bronchi. Many disease processes can result in bronchiectasis, including previous pneumonia or other lower respiratory tract infection, immune deficiency (particularly in children), congenital airway abnormality and aspiration injury (foreign body, gastrointestinal contents or noxious gases) but often the cause is unknown.

Symptoms of bronchiectasis can vary from intermittent episodes of expectoration related to localised infection in the affected region of the lung, to persistent daily expectoration of large volumes of purulent sputum. There may be other non-specific respiratory symptoms, including shortness of breath, chest pain and haemoptysis.

Some organisms, for example P. aeruginosa, can be difficult to eradicate if they colonise the lower respiratory tract in people with bronchiectasis. Colonisation with P. aeruginosa is associated with worse symptoms and quality of life scores than colonisation with other bacteria and may lead to accelerated decline in forced expiratory volume in 1 second (FEV1).

Alternative treatment options

The aims of treatment for non-cystic fibrosis bronchiectasis are to maintain or improve lung function by identifying and treating any underlying cause; to reduce exacerbations, control symptoms and improve quality of life; and, in children, to achieve normal growth and development. Treatments may include airway clearance using physiotherapy, pulmonary rehabilitation, antibiotics, bronchodilators (beta-2 agonists and anticholinergics) and surgery. There is little evidence to support using inhaled corticosteroids (except in people with comorbid asthma) or mucolytics, and no evidence to support the routine use of oral corticosteroids or leukotriene receptor antagonists in people with bronchiectasis.

The British Thoracic Society guideline for non-CF bronchiectasis recommends that antibiotics should be given for exacerbations that present with an acute deterioration and worsening symptoms (cough, increased sputum volume or change of viscosity, increased sputum purulence with or without increasing wheeze, breathlessness or haemoptysis) and/or systemic illness. Sputum culture is recommended to guide antibiotic therapy: empirical antibiotics should be given until the results are known. The first-line treatment is generally amoxicillin or clarithromycin (in people who are allergic to penicillin) for 14 days.

The British Thoracic Society guideline for non-CF bronchiectasis recommends oral ciprofloxacin for people with confirmed P. aeruginosa infection. However, the guideline notes that there is a significant chance of antibiotic resistance, with poor clinical response, after repeated courses of quinolones. The guideline states that if there is no response to oral ciprofloxacin, monotherapy with an appropriate intravenous antibiotic should be considered. It also recommends that, to reduce the development of drug resistance, combination antibiotic therapy should be considered for infections caused by strains of P. aeruginosa that are resistant to 1 or more antipseudomonal antibiotics (including ciprofloxacin) or if the clinician suspects the person will need many subsequent antibiotic courses. It outlines strategies for eradicating P. aeruginosa from the sputum of people with cystic fibrosis and notes that individual clinicians will decide which and how aggressive a strategy to use in people with non-cystic fibrosis bronchiectasis.

The British Thoracic Society recommends that people with non-cystic fibrosis bronchiectasis who have 3 or more exacerbations per year that need antibiotic therapy, or who have fewer exacerbations that are causing significant morbidity, should be considered for long-term oral or nebulised antibiotics. It also advises using long-term nebulised antibiotics (gentamicin, tobramycin or colistimethate sodium) in people who have chronic P. aeruginosa infection, with the choice of antibiotic guided by the results of tests for antibiotic sensitivity. The British Thoracic Society notes that further studies are needed to address the optimal antibiotic choice and doses.

When nebulised antibiotic treatment is used, the British Thoracic Society advises that a multidisciplinary team that includes a chest physician, physiotherapist and respiratory nurse should coordinate care; that the person should receive ongoing support once treatment is started; and that compressors and nebulisers that meet performance and safety standards should be used. See the European Respiratory Society's guidelines on nebuliser treatment.