Evidence strengths and limitations

Evidence strengths and limitations

No published randomised controlled trials (RCTs) have investigated the use of nebulised or inhaled colistimethate sodium for non-cystic fibrosis bronchiectasis.

Four case series were identified that reported the use of nebulised colistimethate sodium in people with non-cystic fibrosis bronchiectasis and bronchial colonisation with Pseudomonas aeruginosa. Case series do not have randomised control groups and are subject to bias and confounding.

White et al. (2012) (n=30), Dhar et al. (2010) (n=19) and Steinfort and Steinfort (2007) (n=18) reported outcomes with nebulised colistimethate sodium, which included exacerbations, hospital admissions, and lung function before and after treatment. Berlana et al. (2011) included 81 people treated with nebulised colistimethate sodium alone, colistimethate sodium plus tobramycin, or tobramycin alone (according to clinical judgement); and primarily compared post-treatment outcomes between the 3 groups, rather than comparing outcomes before and after treatment with nebulised colistimethate sodium.

The case series provide only limited evidence for the effectiveness and safety of inhaled colistimethate sodium in people with non-cystic fibrosis bronchiectasis. All the case series were small, which may mean they have insufficient statistical power to detect differences in outcomes. Also, all reported on treatment in a single medical centre only, which may lead to selection bias and limits the generalisability to a wider population. Two of the case series were retrospective (White et al. 2012 and Dhar et al. 2010) and therefore dependent on the accuracy of the recorded data.

The case series by White et al. (2012) and Dhar et al. (2010) included only people with non-cystic fibrosis bronchiectasis. However, those by Steinfort and Steinfort (2007) and Berlana et al. (2011) also included small numbers of people with chronic obstructive pulmonary disease and chronic bronchial sepsis, which may affect the applicability of the results.

A range of doses was used in the case series; therefore the optimal dose of colistimethate sodium for non-cystic fibrosis bronchiectasis is unclear. All the case series reported using nebulised colistimethate sodium at dose of 1 or 2 million units twice daily except Steinfort and Steinfort (2007), which reported a dose of 30 mg daily (estimated to be around 375,000 units). The duration of treatment with nebulised colistimethate sodium varied in the individual case series, although it was given long term. In the Pseudomonas eradication protocol reported by White et al. (2012), colistimethate sodium was given for 3 months; Berlana et al. (2011) reported use for at least 3 months; and both Dhar et al. (2010) and Steinfort and Steinfort (2007) reported use for at least 6 months.

From the case series, it is not possible to conclude that observed post-treatment effects were due to colistimethate sodium alone. For example, the Pseudomonas eradication protocol reported by White et al. (2012) included treatment with other intravenous and oral antibiotics and antibiotics other than those set out in the protocol were used in 8 out of 30 people, mainly because of drug allergy or intolerance. Dhar et al. (2010) excluded from their study people who had used prophylactic macrolide treatment for more than 4 weeks, but no other antibiotic use is discussed. Steinfort and Steinfort (2007) did not report whether there was any other antibiotic use. None of these 3 case series discussed the use of other respiratory drugs. Berlana et al. (2011) reported that people taking colistimethate sodium, tobramycin or both took various respiratory drugs (for example, bronchodilators and corticosteroids) and supplemental oxygen, as well as other antibiotics.

All of the case series used nebulised colistimethate sodium. No studies were identified that investigated the use of the colistimethate sodium dry powder inhaler (Colobreathe, Turbospin) in people with non-cystic fibrosis bronchiectasis.

An RCT, Inhaled Promixin in the treatment of non-cystic fibrosis bronchiectasis, has been completed but not yet published. Once fully published and peer-reviewed, this study and other RCTs investigating nebulised or inhaled colistimethate sodium for treating non-cystic fibrosis bronchiectasis may give a better indication of the safety and efficacy for this indication.