Nebulised anti-pseudomonal antibiotics for cystic fibrosis.
BACKGROUND
Lung damage associated with persistent infection by Pseudomonas aeruginosa is the major cause of morbidity and mortality in people with cystic fibrosis. Nebulised antibiotics are commonly used for treatment of this infection.


OBJECTIVE
To examine the evidence that nebulised anti-pseudomonal antibiotic treatment in patients with cystic fibrosis reduces frequency of exacerbations of infection, improves lung function, quality of life and survival. To assess adverse effects of nebulised anti-pseudomonal antibiotic treatment.


METHODS
Trials were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group clinical trials register. Companies which marketed nebulised anti-pseudomonal antibiotics were contacted for information on unpublished trials. Date of the most recent search of the Group's specialised register: November 1999.


METHODS
Trials were selected if, nebulised anti-pseudomonal antibiotics treatment was used in patients with cystic fibrosis, treatment was used for four weeks or more, allocation to treatment was randomised or pseudo-randomised, and there was a placebo or a no placebo control group.


METHODS
References to nebulised antibiotics were retrieved from the register. Two reviewers independently selected trials from this sample according to the criteria. Each judged the quality of selected trials. One reviewer extracted data from these trials.


RESULTS
Ten trials with 758 participants were included in the review. Sixty eight % of participants were in one trial. Duration of trials ranged from one to 32 months. There was large variation in study design and outcome measures which limited meta-analysis. Lung function measured as forced expired volume in one second (FEV1) was generally better in the treated groups than in control groups but a pooled estimate of effect was not possible. In the largest trial of 520 participants the FEV1 was 11.9% predicted (95% confidence interval 8.1to 15.6) higher in the treated group than in the placebo control group after 5 months. In three trials with 581 participants the number of participants having at least one hospital admission during a trial was reduced in the groups treated with nebulised antibiotics, odds ratio 0.69 (95% confidence Interval 0.50 to 0.96). In two trials with 591 participants the number of participants having and at least one course of antibiotic therapy was reduced in the treated group, odds ratio 0.62 (95% confidence interval 0.45 to 0.87). There was no evidence of renal or auditory toxicity. Resistance to antibiotic increased more in the antibiotic treated group than in placebo group. The most evidence for a single drug is for tobramycin, which was used in total daily doses from 40mg to 1800mg.


CONCLUSIONS
Nebulised anti-pseudomonal antibiotic treatment improves lung function and reduces frequency of exacerbations of infection in people with cystic fibrosis. There is a need for more evidence for effect on quality of life and survival, for longer duration trials to determine if this benefit is maintained and to determine the significance of development of antibiotic resistant organisms.
Ryan
G
G
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia, 6008. gryan@cyllene.uwa.edu.au
Mukhopadhyay
S
S
Singh
M
M
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D003550:Cystic Fibrosis / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D009330:Nebulizers and Vaporizers; D011552:Pseudomonas Infections / Q000209:etiology* / Q000517:prevention & control*; D012141:Respiratory Tract Infections / Q000209:etiology* / Q000517:prevention & control*
D000336:Aerosols; D000900:Anti-Bacterial Agents