Evidence review: safety

Adverse effects listed in summaries of product characteristics

Colistimethate sodium (Colomycin injection and Promixin powder for nebuliser solution, and Colobreathe dry powder for inhalation) is very commonly associated with adverse respiratory effects (affecting at least 1 in 10 people) including cough, dyspnoea (shortness of breath), bronchospasm and sore throat. Colobreathe also very commonly (in at least 1 in 10 people) causes dysphonia (hoarseness and difficultly speaking) and dysgeusia (distorted taste), and is associated (in at least 1 in 100 people) with nausea and vomiting, tinnitus, balance disorder, headache, arthralgia and fatigue.

Adverse effects in case series

White et al. (2012) did not report adverse effects. However, they stated that 3 out of 30 patients (10%) did not receive nebulised colistimethate sodium because of intolerance.

Dhar et al. (2010) did not report adverse effects. Out of the 19 patients, 2 (11%) stopped treatment, 1 in error and 1 because of lack of efficacy.

In Steinfort and Steinfort (2007), no adverse effects were reported by the 18 people who received colistimethate sodium over a period of 6–116 months. One person stopped treatment because of perceived ineffectiveness.

In Berlana et al. (2011), safety analyses were undertaken and included all people who received at least 1 day of treatment with the inhaled therapy. Drug-related adverse events were experienced by 29 out of 50 people who took colistimethate sodium alone (58%) and 20 out of 72 people who took tobramycin alone (28%). There was no significant difference in adverse events between colistimethate sodium and tobramycin (p=0.24).

There was also no significant difference in the number of withdrawals because of adverse events in the colistimethate sodium or tobramycin groups (13/50 [26%] compared with 9/72 [13%], borderline non-significant p=0.06).

Twelve patients (14.8%) died during the case series timeframe (all from respiratory causes), with no significant differences between the treatment groups.

The most common adverse events seen with colistimethate sodium were shortness of breath, bronchospasm and cough (each affecting 6/50 people, 12%), wheeze (5/50, 10%) and dry mouth (3/50, 6%).

Antimicrobial resistance

In September 2013, the Department of Health published a 5-year strategy to improve the knowledge and understanding of antimicrobial resistance and conserve and steward the effectiveness of existing treatments. This strategy has important implications for the use of antibiotics and the need for good husbandry around their use.

The British Thoracic Society guideline for non-CF bronchiectasis points out that long-term use of antibiotics may result in antibiotic resistance in individual patients and alternative antibiotics should be chosen depending on sensitivity results. According to the summary of product characteristics for Promixin, P. aeruginosa has been reported as acquiring resistance to colistimethate sodium during clinical use. Susceptibility testing should be performed for people who are treated on a long-term basis, at regular clinic visits and whenever the person experiences an exacerbation.

In Berlana et al. (2011), bacterial resistance developed in 8% of courses of colistimethate sodium alone (2/26), compared with 55% (18/33) of courses of tobramycin alone. Compared with tobramycin alone, colistimethate sodium alone statistically significantly reduced the risk of developing resistance to any inhaled antibiotic (p<0.05) or to colistimethate sodium (p<0.01). No resistance to colistimethate sodium was recorded among bacterial isolates obtained in Steinfort and Steinfort (2007) or White et al. (2012).