Inhaled antibiotics for treatment of adults with non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis.

BACKGROUND: Inhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations. METHODS: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154. RESULTS: Twelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70-5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81-18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28-1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82-0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV1, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35-3.27) at the end of therapy, with a number needed to treat of 6. CONCLUSIONS: IA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.

Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. METHODS: A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded. RESULTS: Five of the 11 studies included had a small sample size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18; I = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18; 95% CI, 0.05 to 0.64; I = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96; 95% CI, 1.30 to 2.96; I = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens. CONCLUSIONS: Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.