Abstract: Four trials with 167 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and two trials (90 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials, but for all trials we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis. Inhaled antibiotics alone versus intravenous antibiotics alone Only one trial (n = 18) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-quality of evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-quality evidence). With regards to our secondary outcomes, one trial (n = 18) reported no difference in the need for additional antibiotics and the second trial (n = 59) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-quality evidence). The single trial (n = 18) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-quality evidence). Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics alone Neither trial reported on quality of life or time off work or school. Both trials measured lung function, but found no difference between groups in forced expiratory volume in one second (one trial, n = 28, very low-quality evidence) or vital capacity (one trial, n = 62). Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (n = 28) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events (very low-quality evidence) and one trial (n = 62) reported no difference in the emergence of antibiotic-resistant organisms (very low-quality evidence). There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.

Plain-language summary: We found four trials with a total of 167 participants, two of which compared inhaled antibiotics alone to intravenous antibiotics alone (77 participants) and two which compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone (90 participants) for treating exacerbations in people with cystic fibrosis. In all trials the inhaled antibiotics were compared to the same antibiotics given intravenously. The numbers of participants in each trial ranged from 18 to 62. Inhaled antibiotics alone versus intravenous antibiotics alone One trial (18 participants) reported a perceived improvement in lifestyle in both groups but neither trial reported on time off work or school. Both trials measured lung function, but neither reported any difference between treatment groups. One trial (18 participants) reported no difference in the need for additional antibiotics and the second trial (59 participants) reported on the time to next exacerbation - there was no difference between inhaled or intravenous antibiotics for either outcome. Only one trial (18 participants) measured adverse events and sputum microbiology, but did not find any difference between treatments for either outcome. Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics alone Neither trial reported on quality of life or time off work or school. Both trials reported lung function, but found no difference between groups. Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (28 participants) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events and one trial (62 participants) reported no difference in the emergence of antibiotic-resistant organisms. We graded the quality of the evidence as very low. We had concerns since none of the trials stated how the participants were diagnosed with CF or how they defined an exacerbation. It was not possible to keep the treatment group secret from the participants as the trials compared different ways of giving the antibiotics and we thought this would likely influence some of the results. We were not sure whether the participants were put into the different groups truly at random and we do not know how this might affect the results.