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. 2020 Apr;46(4):766-770.
doi: 10.1007/s00134-019-05890-w. Epub 2020 Jan 8.

Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: understanding nebulization of aminoglycosides and colistin

J J Rouby  1 , C Sole-Lleonart  2   3 , J Rello  4   5   6 ; European Investigators Network for Nebulized Antibiotics in Ventilator-associated Pneumonia
Collaborators, Affiliations

Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: understanding nebulization of aminoglycosides and colistin

J J Rouby et al. Intensive Care Med. 2020 Apr.

Erratum in

No abstract available

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Conflict of interest statement

JR received grant support from BAYER and served in the advisory board for BAYER and speakers bureau for Norma Helas. OM served as a consultant for SANOFI. SE declares having received consultancies from Aerogen Ltd, La Diffusion Technique Française and Bayer Healthcare, research support from Aerogen Ltd, Fisher & Paykel healthcare, Hamilton medical, travel reimbursements from Aerogen Ltd and Fisher & Paykel. JD and PFL received an unrestricted grant from Aerogen Ltd for their study [14]. JMQ currently received grant from Sino-European Cooperative Clinical Research Project “Evaluation of clinical efficacy and safety of QBW251 in patients with severe bronchiectasis”. MB has participated in advisory boards and/or received speaker honoraria from Achaogen, Angelini, Astellas, Bayer, Basilea, Biomerieux, Cidara, Gilead, Menarini, MSD, Nabriva, Paratek, Pfizer, Roche, Melinta, Shionogi, Tetraphase, VenatoRx and Vifor and has received study grants from Angelini, Basilea, Astellas, Shionogi, Cidara, Melinta, Gilead, Pfizer and MSD. JAR has received grants or consultancy fees from MSD, Accelerate Diagnostics, Biomerieux, Pfizer, The Medicines Company and Cardeas Pharma. KP has received speaker’s Honoraria from MSD and Pfizer. GD has received grants and speaker’s Honoraria from Pfizer, InfectoPharma, Virogates, Glenmark india, Clinigen, Nabriva, Menarini and ELPEN. AK has received research grant from Norma Helas. The other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Nebulization of amikacin and colistin: from the nebulizer’s chamber to lung deposition and urinary excretion. a–c Mesh nebulizers positioned 15 cm from the Y piece, and made of a domed aperture plate with 1000 precision-formed holes which vibrates at 100 kHz. The vibration-induced micro-pumping effect produces a fine particle, low velocity aerosol. The mass median aerodynamic diameter depends and the holes’ diameter; d specific respirator tubings with smooth angle and inner surface; e–i illustrations of tracheobronchial deposition of aerosol particles. Scintigraphic images representing airways and lung deposition of an aerosol of diethylenetriaminepentaacetic acid labeled with technetium-99 m are shown in e–h. Images were obtained in four postoperative neurosurgery patients without pulmonary disease ventilated either in volume-controlled ventilation (n = 2, e and f) or in pressure support ventilation (n = 2, g and h). A part of the aerosol reached the lung periphery, but the majority impacted proximally in the trachea and large bronchi. Lung deposition was significantly greater in patients on volume-controlled mechanical ventilation; whereas, extrapulmonary deposition was significantly lower. i Illustrates the contamination of the bronchoscope during the BAL procedure (the red color indicates high aerosol bronchial concentration). Reproduced from Dugernier et al. [14] and Rouby et al. [5] with the permission of the publishers. j, k Illustrate the systemic diffusion of nebulized colistin (j) and aminoglycosides (k) in patients with ventilator-associated tracheobronchitis and in piglets with inoculation pneumonia. Amikacin plasma concentrations after intravenous administration are represented in blue and in black following nebulization. The nebulized dose was equal to the intravenous dose plus extrapulmonary deposition, so that equivalent amount entered the respiratory system either by the trachea (nebulization) or by the pulmonary artery (intravenous administration). Reproduced from Athanassia et al. [8] and Rouby et al. [1] with the permission of the publishers. TV tidal volume, RF respiratory frequency, bpm breaths per minute, I/E inspiratory:expiratory ratio; PEEP positive end-expiratory pressure, BAL bronchoalveolar lavage; m IU million International Units
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References

    1. Rouby JJ, Bouhemad B, Monsel A, et al. Aerosolized antibiotics for ventilator-associated pneumonia: lessons from experimental studies. Anesthesiology. 2012;117:1364–1380. doi: 10.1097/ALN.0b013e3182755d7a. - DOI - PubMed
    1. Dhanani JA, Diab S, Chaudhary J, et al. Lung pharmacokinetics of tobramycin by intravenous and nebulized dosing in a mechanically ventilated healthy ovine model. Anesthesiology. 2019;131:344–355. doi: 10.1097/ALN.0000000000002752. - DOI - PubMed
    1. Rello J, Rouby JJ, Sole-Lleonart C, et al. Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients. Clin Microbiol Infect. 2017;23:640–646. doi: 10.1016/j.cmi.2017.03.018. - DOI - PubMed
    1. Rello J, Solé-Lleonart C, Rouby JJ, et al. Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases. Clin Microbiol Infect. 2017;23:629–639. doi: 10.1016/j.cmi.2017.04.011. - DOI - PubMed
    1. Rouby JJ, Monsel A. Nebulized antibiotics: epithelial lining fluid concentrations overestimate lung tissue concentrations. Anesthesiology. 2019;131:229–322. doi: 10.1097/ALN.0000000000002824. - DOI - PubMed

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