Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.

Antibiotic treatment adequacy and death among patients with Pseudomonas aeruginosa airway infection.

OBJECTIVE: The effect of antibiotics on survival in patients with pulmonary Pseudomonas aeruginosa is controversial. The aim of this study is to i) determine the prevalence of adequate antibiotic treatment of P. aeruginosa in an unselected group of adult non-cystic fibrosis patients and ii) to assess the overall mortality in study patients treated with adequate vs. non-adequate antibiotics. METHODS: Prospective, observational study of all adult patients with culture verified P. aeruginosa from 1 January 2010-31 December 2012 in Region Zealand, Denmark. Patients with cystic fibrosis were excluded. Adequate therapy was defined as any antibiotic treatment including at least one antipseudomonal beta-lactam for a duration of at least 10 days. Furthermore, P. aeruginosa had to be tested susceptible to the given antipseudomonal drug and treatment had to be approved by senior clinician to fulfil the adequate-criteria. RESULTS: A total of 250 patients were identified with pulmonary P. aeruginosa. The vast majority (80%) were treated with non-adequate antibiotic therapy. All-cause mortality rate after 12 months was 49% in adequate treatment group vs. 52% in non-adequate treatment group. Cox regression analysis adjusted for age, gender, bacteraemia, comorbidities and bronchiectasis showed no significant difference in mortality between treatment groups (adequate vs. non-adequate: hazard ratio 0.95, 95% CI 0.59-1.52, P = 0.82). CONCLUSION: Adequate antipseudomonal therapy was only provided in a minority of patients with pulmonary P. aeruginosa. Adequate therapy did not independently predict a favourable outcome. New research initiatives are needed to improve the prognosis of this vulnerable group of patients.