S3 guidelines on pulmonary disease in cystic fibrosis. Module 1: diagnostics and therapy after initial detection of Pseudomonas aeruginosa

Cystic fibrosis (CF) is one of the most frequent autosomal recessive inherited diseases in the Caucasian population. A genetic defect in the CFTR gene leads to a reduction in chloride ion transport in cell membranes. The resulting dehydration of the wet epithelial film causes a reduction in secretion clearance. The consequence is a multiorgan disease. The pulmonary manifestation with chronic infections and inflammation is the leading cause of death. Acute and chronic infections caused by Pseudomonas aeruginosa (PA) can lead to a decline in lung function and have a direct negative effect on the chances of survival. The development of the first clinical S3 guideline for cystic fibrosis aims at standardizing and optimizing the diagnostics and therapy in Germany, Austria and Switzerland after the initial detection of P. aeruginosa. Simultaneously, this should provide an impulse for further research activities and developments of guidelines. On the basis of a Cochrane review a comprehensive up to date literature search was carried out for the period from 1995 to November 2011 (updated September 2014). Of the resulting 286 original papers, 6 randomized clinical trials and 8 additional eradication trials with low evidence were identified as relevant and were evaluated. Experts from 13 scientific and medical societies and associations evaluated the evidence by means of these original articles and with the help of national and international guidelines and consensus documents as a basis for the formulation of 36 recommendations in a nominal group process. The evaluation of the eradication studies demonstrated that early antibiotic eradication therapy is effective for patients with CF. Which therapy regimen is the most promising, cannot be decided due to a limited number of comparative studies. After evaluation of all the evidence the following core recommendations are given: the early eradication should be carried out by means of inhaled tobramycin for 4 weeks or by means of oral ciprofloxacin combined with inhaled colistin for 3 weeks. In cases where inhalation is not possible, an intravenous combination therapy should be taken into consideration as a possibility. If a therapy with inhalative and oral antibiotics does not lead to eradication, a combination therapy should be carried out with intravenous antibiotics and inhalative colistin. A sequential combination of intravenous and inhalative antibiotics is recommended for a pulmonary exacerbation and initial detection of PA. The early eradication therapy of PA is effective in cystic fibrosis and can be carried out according to the current guidelines. In the studies available no superiority of one particular therapy regimen could be shown. Further comparative studies as well as studies on the involvement of the upper respiratory tract should be performed in the future.