Nebulized colistin for treatment of ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: we still need to straighten out the dose!
Honore et al. Critical Care
Nebulized colistin for treatment of ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: we still need to straighten out the dose!
Patrick M. Honore 0 1
Rita Jacobs 0 1
Inne Hendrickx 0 1
Elisabeth De Waele 0 1
Jouke De Regt 0 1
Herbert D. Spapen 0 1
0 References 1. Zampieri FG, Nassar Jr AP, Gusmao-Flores D, Taniguchi LU, Torres A, Ranzani OT. Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis. Crit Care. 2015;19:150. 2. Ratjen F, Rietschel E, Kasel D, Schwiertz R , Starke K, Beier H, et al. Pharmacokinetics of inhaled colistin in patients with cystic fibrosis. J Antimicrob Chemother. 2006;57:306-11. 3. Athanassa ZE, Markantonis SL, Fousteri MZ, Myrianthefs PM, Boutzouka EG , Tsakris A, et al. Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients. Intensive Care Med. 2012;38:1779-86. 4. Gurjar M. Colistin for lung infection: an update. J Intensive Care. 2015;3:3. 5. Lu Q, Luo R, Bodin L, Yang J, Zahr N , Aubry A, et al. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug- resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology. 2012;117:1335-47
1 ICU Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel , 101 Laarbeeklaan, 1090 Jette, Brussels , Belgium
Abbreviations CMS: Colistimethate sodium; MDR-GNB: Multidrug-resistant Gram-negative bacteria; VAP: Ventilator-associated pneumonia.
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We applaud the extensive systematic review and
metaanalysis by Zampieri and colleagues on inhaled
antibiotics for ventilator-associated pneumonia (VAP) [1] but
would like to add some comments regarding inhaled
colistin for treatment of VAP caused by
multidrugresistant Gram-negative bacteria (MDR-GNB).
In patients with cystic fibrosis, the equivalent of 160
mg colistimethate sodium (CMS) produced high and
therapeutic endobronchial concentrations [2]. However,
to be effective in VAP caused by MDR-GNB, colistin
must attain pulmonary concentrations that substantially
exceed minimal plasma inhibitory levels for these
microorganisms. Colistin aerosols used in the predominantly
retrospective and observational studies summarized by
Zampieri and colleagues contained CMS doses ranging
from 80 to 300 mg [1]. These doses may be insufficient
to grant any significant or additional therapeutic value
to inhaled colistin, especially when used together with
intravenous antibiotics. Indeed, a total daily inhaled dose
of 240 mg CMS was found to be inadequate to treat
lung infection caused by MDR-GNB [3]. A recent review
recommended inhalation of 160 mg CMS every 8 h for
severe pulmonary infections [4]. Finally, a daily dose of
1,200 mg inhaled CMS used in monotherapy or
associated with a 3-day course of intravenous aminoglycosides
cured VAP caused by MDR-GNB as effectively as VAP
caused by β-lactam susceptible GNB [5]. In contrast
with intravenous administration, high doses of nebulized
colistin are not associated with an increased risk of
kidney injury, even when given for a prolonged period of
time [5].
We strongly salute aerosolized colistin as an important
alternative or adjunct therapy to treat VAP caused by
MDR-GNB, provided that the daily inhaled dose is
sufficiently high.
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