Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis: a pilot study.
BACKGROUND
Pulmonary administration of colistin is one of the antimicrobial treatments used in Cystic Fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. Dry powder inhalation of colistin may be an attractive alternative to nebulization of colistin. However, nebulized colistin can cause bronchoconstriction in CF patients. Therefore, in the progress of developing a dry powder formula, the choice of the inhaler and its contents should be guided by optimal efficacy and the least possible side effects. To investigate the side effects, a study was initiated to compare the tolerability of colistin sulphate to colistin sulphomethate per nebulization in CF-patients.


METHODS
Nine CF-patients chronically infected with P. aeruginosa participated in a double blind, randomized cross over study. On two visits to the outpatient clinic, patients were submitted to either nebulized colistin sulphate or colistin sulphomethate solution. Lung function tests were performed immediately before and 15 and 30 min after nebulization.


RESULTS
Nebulization of colistin sulphate caused a significant larger mean decrease in lung function compared to nebulized colistin sulphomethate. A significant decrease in mean changes (SD) in FEV1 at 30 min and FVC at 15 and 30 min after nebulization compared to baseline of -7.3% (8.6%), -5.7% (7.3%) and -8.4% (7.5%) respectively was seen after colistin sulphate nebulization compared to colistin sulphomethate (P < 0.05). Seven patients were not able to complete the nebulization of colistin sulphate because of throat irritation and severe cough.


CONCLUSIONS
Based on these results it was concluded that inhalation with nebulized colistin sulphate is not suitable for treatment of CF patients chronically infected with P. aeruginosa. Colistin sulphomethate is the drug of choice for pulmonary administration of colistin.
Central Hospital Pharmacy The Hague, The Hague, The Netherlands. e.westerman@ahz.nl
E M
EM
Westerman
P P H
PP
Le Brun
D J
DJ
Touw
H W
HW
Frijlink
H G M
HG
Heijerman
D000280:Administration, Inhalation; D000328:Adult; D003091:Colistin / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D010865:Pilot Projects; D011336:Probability; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D003091:Colistin