Abstract
Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20–25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.
Highlights
Polymyxins are non-ribosomal, cyclic oligopeptide antimicrobials, produced by the Gram-positive, spore-forming rod Bacillus aerosporus that were identified in 1946 from the soil of market gardens in England [1]
These results suggest that colistin methanesulfonate sodium (CMS) and colistin accumulate in the lung compartment
Well-designed multicenter randomized control trials (RCTs) are lacking, there is a body of evidence suggesting that nebulized CMS is efficient for treating lower respiratory tract infections caused by MDR Gram-negative bacteria (GNB)
Summary
Polymyxins are non-ribosomal, cyclic oligopeptide antimicrobials, produced by the Gram-positive, spore-forming rod Bacillus aerosporus that were identified in 1946 from the soil of market gardens in England [1]. CMS is an essentially inactive prodrug that is hydrolyzed to multiple components with direct bactericidal activity. Among these colistin components, two are predominant, colistin A and colistin B. ~ 80 mg CMS = one million IU CMS = ~ 33.3 mg CBA This narrative review is focused on nebulized CMS as a treatment of ventilatorassociated pneumonia (VAP) in critically ill patients. It has three aims: (1) to report the historical background supporting its use in critically ill patients; (2) to describe the complex and partially unknown PK/PD of intravenous and nebulized CMS; (3) to suggest future research priorities for CMS nebulization in patients with VAP caused by extensive drug-resistant (XDR) GNB
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
