Polymyxins Nebulization over Intravenous Injection: Pharmacokinetics and Pharmacodynamics-Based Therapeutic Evaluation

Abstract

Polymyxins are the last line potential antibiotics against multi-drug resistant gram-negative bacteria and consist of two sister antibiotics: Polymyxin B and colistin (polymyxin E). Intravenous use of polymyxins was started from a long ago in the treatment of serious gram-negative infections and once their uses were restricted due to potential adverse drug reactions, such as nephrotoxicity and neurotoxicity. Lack of in vivo clinical studies on polymyxins mostly, in human body makes the pharmacokinetics and pharmacodynamics of polymyxin B and colistin unclear in many aspects, such as the distribution of polymyxins in different compartments of lung. The nebulization of polymyxins is practicing very limitedly and lack of clinical evidence has not justified this administration technique yet properly to date. The main objective of this review study was to evaluate the pharmacokinetic and pharmacodynamic properties of intravenous and nebulized polymyxins and the related therapeutic potentialities. Aerosolized polymyxins directly administered to the respiratory tract was found with higher drug concentration in different subcompartments of lungs than the intravenous administration and sustainably meets the minimum inhibitory concentration locally with superior bactericidal properties in respiratory tract infections. In contrast, intravenous administration of polymyxins shows similar anti-infective superiority in other organs, Hasan; JPRI, 25(4): 1-10, 2018; Article no.JPRI.47507 2 such as blood, urinary tract etc. So, during this alarming situation of rapidly emerging multidrugresistant organisms in human communities, therapeutic administration techniques of last resort polymyxins should be clinically evidence-based for achieving optimum therapeutic outcomes with minimum chance of adverse drug reactions. Mini-review Article

The resistance growing trend of common gramnegative bacteria to the potential antibiotics over three consecutive years: a single center experience in Bangladesh

“…3,12 This increasing trend of resistant organisms causes more infectionassociated hospitalization, treatment failure, mortality and treatment cost. 8,13 In this study, the sensitivity patterns of meropenem, amikacin, ceftazidime and cefepime were significantly lower (all were found below 50% of the sensitivity level) than last resort polymyxin B and colistin to A. baumannii in every selected year. Both polymyxin B and colistin are under the polymyxins group and this is considered as one of the last resort antibiotic groups, globally.…”

“…Both polymyxin B and colistin are under the polymyxins group and this is considered as one of the last resort antibiotic groups, globally. 8 Tigecycline is another last resort antibiotic 14 but, the use of tigecycline is very limited by the prescribers with limited sensitivity data.…”

“…3,6 In general, the most popular and potential antibiotics are meropenem, amikacin, ceftazidime, cefepime, polymyxin B and colistin (polymyxin E). 7,8 These antibiotics are mostly considered as the potential antibiotics when different types of infections are mostly caused by the most common gram-negative bacteria (GNB) including Escherichia coli, Klebsiella pneumonia, Acinetobacter baumannii and Pseudomonas aeruginosa. 8 The main objective of this study was to observe the resistance developing trend of these common gramnegative bacteria against the few commonly used potential antibiotics over the recent 3 consecutive years in a single hospital setup.…”

The Susceptibility of MDR-K. Pneumoniae to Polymyxin B Plus its Nebulised Form Versus Polymyxin B Alone in Critically Ill South Asian Patients

“…Studies have reported that a relatively high polymyxin B concentration is significantly achieved in lungs’ sub-compartments after its direct aerosolised administration, and exhibits better microbial eradication compared to intravenous polymyxin B. Conversely, a single-route intravenous administration of polymyxin B in the treatment of severe pneumonia in high-risk ventilated patients of this study, was found to be less efficient in achieving microbial eradication [ 25 , 26 ].…”

Aerosolized Plus Intravenous Polymyxin B Versus Colistin in the Treatment of Pandrug-Resistant Klebsiella Pneumonia-mediated Ventilator-Associated Pneumonia: A Retrospective Cohort Study in Bangladesh

“…To date, in-vivo data are limited regarding the pharmacokinetics of polymyxins in lung tissue after its intravenous or aerosolized administration and the susceptibility of PDR KP strains to polymyxins at differential drug-concentration in the lung tissue. Moreover, the paucity of data on polymyxins’ dose-mediated toxicity in patients with VAP develops conflicts regarding therapeutic modification [ 12 , 13 ]. The optimized therapeutic armamentarium with the last-hope polymyxins may be effective against the PDRKP strains causing VAP.…”