Therapeutic Specification of the Last Resort Polymyxins: An Intelligent Approach

Abstract

Polymyxins, especially polymyxin B and colistin (polymyxin E), are the last resort antibiotics among a few reserve antibiotics still showing potentiality against Gram-negative superbugs. Globally, during the alarming situation of fast-spreading antibiotic resistance in Gram-negative bacteria, the therapeutic application of polymyxins should be rational and target-specific considering their pharmacokinetic (PK) and pharmacodynamic (PD) characteristics. Intravenous polymyxin B shows relatively higher plasma protein binding and excessive renal tubular reabsorption; it invariably exists in the plasma for longer periods, maintaining the minimum inhibitory concentration (MIC) properly, and mostly are excreted out through a nonrenal pathway. On the other hand, intravenous inactive colistimethate sodium is bio-converted in the blood and kidneys into the active colistin moiety that manifests relatively higher colistin concentration in the urinary tract for longer duration possessing the MIC statically. This study comprehensively evaluated the PK and PD data of polymyxins assuming that the therapeutic specification of polymyxin B in bloodstream infections and colistin in urinary tract infections caused by multidrug-resistant Gram-negative bacteria may be an intelligent approach during the emergence of antibiotic resistance. The therapeutic specification of polymyxins may effectively reduce the progression of polymyxin resistance and optimize its therapeutic outcomes in the treatment of life-threatening infections.

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

“…The use of polymyxin B and colistin as last-line therapy in intravenous and aerosolized form in serious infections with MDR pathogens has been attributed in clinical practice over the last couple of decades [ 12 ]. In practice, in severe upper or lower respiratory tract infections, such as VAP, aerosolized polymyxins are currently more popular among the clinicians due to its outweighed therapeutic benefits over intravenous use [ 13 , 19 , 20 ]. However, clinical data related to the use of polymyxins in the treatment of PDR K. pneumoniae VAP mostly in South Asian population is limited [ 21 ].…”

“…Colistin is the bioactive form of CMS (administration form) and following an intravenous single dose of CMS, only 20% to 25% of the total CMS is rapidly converted to colistin-base activity (CBA) in-vivo , and the major portion of the drug is excreted through kidney as unchanged from of drug [ 20 , 22 ]. Following an intravenous dose of 150 mg CBA, the maximum plasma concentration ( C max, Plasma ) of colistin ranges from 0.4 to 0.77 mg/Liter of blood [ 22 ].…”