Overestimating VELF would have led to underestimation of amikacin

Overestimating VELF would have led to underestimation of amikacin concentrations in ELF. On the other hand, because of possible bronchial backflow Crizotinib ROS1 during BAL collection, BAL fluids might have been contaminated by tracheal secretions, whose amikacin concentrations are very high, and that would have overestimated the concentrations [27]. Finally, amikacin concentrations varied widely among patients. This variability is probably due to multiple factors, including aeration, ventilator settings, ventilatory circuit and patient’s specific factors. These factors may deserve to be evaluated in a specifically designed study. However, variability due to poor nebulization reproducibility cannot be excluded. But, the ELF amikacin concentrations always exceeded the MIC of microorganisms responsible for VAP; hence, these variations probably have no clinical implications.

ConclusionsAmikacin aerosolization with the PDDS vibrating mesh nebulizer achieved high concentrations in ELF with little systemic absorption and accumulation, thereby confirming recent data obtained in healthy volunteers [22]. The clinical efficacy of adjunctive aerosol therapy remains to be determined.Key messages? Amikacin aerosolization with the PDDS achieved high concentration in the trachea and alveolar epithelial lining fluid.? Amikacin systemic absorption is low with this device.? The clinical implication of nebulization with this device remains to be determined.

AbbreviationsAUC: area under curve; BAL: bronchoalveolar lavage; Cmax: maximum serum amikacin concentration; ELF: epithelial lining fluid; FiO2: fraction of inspired oxygen; HAP: hospital-acquired pneumonia; HCAP: healthcare-associated pneumonia; IQR: interquartile range; MIC: miminum inhibitory concentration; PDDS: pulmonary delivery drug system; Tmax: time to maximum serum amikacin concentration; VAP: ventilator-associated pneumonia; VELF: volume of alveolar epithelial lining fluid.Competing interestsJC received lecture fees from Nektar Therapeutics. KC and DG were Nektar Therapeutics employees at the time of the study. The other authors declare that they have no competing interests.Authors’ contributionsCEL, KC, DG and JC participated in the conception and design of the study, analyzed and interpreted the data, and drafted the manuscript. CEL, MC, KG, JJ, JK, CW and JC participated in data collection.

All authors read and approved the final manuscript.AcknowledgementsThe authors would like to thank Gregory Janis from MedTox for his expert contribution to the assay development section. This study was supported by a grant from Nektar Therapeutics.
In the 1990s, low tidal volume and pressure-limited ventilation Dacomitinib were supposed to lower mortality in patients mechanically ventilated for acute respiratory distress syndrome (ARDS) [1]. In a way, this was the beginning of lung-protective ventilation strategies [2].

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