Details

Autor(en) / Beteiligte

• Rouby, Jean-Jacques
• Monsel, Antoine
• Ehrmann, Stephan
• Bouglé, Adrien
• Laterre, Pierre-François

Titel

The INHALE trial: multiple reasons for a negative result

Ist Teil von

• The Lancet infectious diseases, 2020-07, Vol.20 (7), p.778-779

Ort / Verlag

London: Elsevier Ltd

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• The presence (or the risk) of a multidrug-resistant pathogen infecting the lungs was justification for administering two intravenous antibiotics in both the amikacin treatment group and the placebo group.2 Antimicrobial bitherapy is not superior to monotherapy in ventilator-associated pneumonia caused by non-resistant, Gram-negative bacteria.3 In the IHNALE trial,1 49% of identified pathogens were not multidrug-resistant and a treatment success of 77% in the placebo group reflected the high efficiency of intravenous bitherapy. [...]an additional benefit from aerosolised amikacin could not be reasonably expected. In 28 patients with ventilator-associated pneumonia treated by nebulised amikacin, amikacin tracheal concentrations were found to be 25 times higher and epithelial lining fluid concentrations were found to be four times higher than the minimum inhibitory concentration of multidrug-resistant, Gram-negative bacteria.4 These concentrations were interpreted as reflecting high amikacin distal lung deposition and justified the administration of 12 mg/kg per day in the INHALE trial. Interestingly, epithelial lining fluid concentrations of tobramycin in ventilated sheep receiving a single nebulisation were 100 times greater than interstitial space fluid concentrations measured by microdialysis.8 These data are highly suggestive of a massive bronchial contamination of the fiberscope and the bronchoalveolar lavage; therefore, elevated epithelial lining fluid concentrations of a nebulised drug can be considered an artefact.9 Finally, the insufficient optimisation of ventilator settings during the nebulisation could have further reduced amikacin distal lung deposition by potentiating the impaction of aerosolised particles on bronchial walls.