Nebulized antibiotics in mechanically ventilated patients: a challenge for translational research from technology to clinical care

Nebulized antibiotic therapy directly targets airways and lung parenchyma resulting in high local concentrations and potentially lower systemic toxicities. Experimental and clinical studies have provided evidence for elevated lung concentrations and rapid bacterial killing following the administration of nebulized antibiotics during mechanical ventilation. Delivery of high concentrations of antibiotics to infected lung regions is the key to achieving efficient nebulized antibiotic therapy. However, current non-standardized clinical practice, the difficulties with implementing optimal nebulization techniques and the lack of robust clinical data have limited its widespread adoption. The present review summarizes the techniques and clinical constraints for optimal delivery of nebulized antibiotics to lung parenchyma during invasive mechanical ventilation. Pulmonary pharmacokinetics and pharmacodynamics of nebulized antibiotic therapy to treat ventilator-associated pneumonia are discussed and put into perspective. Experimental and clinical pharmacokinetics and pharmacodynamics support the use of nebulized antibiotics. However, its clinical benefits compared to intravenous therapy remain to be proved. Future investigations should focus on continuous improvement of nebulization practices and techniques. Before expanding its clinical use, careful design of large phase III randomized trials implementing adequate therapeutic strategies in targeted populations is required to demonstrate the clinical effectiveness of nebulized antibiotics in terms of patient outcomes and reduction in the emergence of antibiotic resistance.