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Abstract
Polymyxin B and colistin (polymyxin E) are polypeptide antibiotics that were developed in the 1940s, but fell into disfavor due to their high toxicity rates. These two antibiotics were previously regarded to be largely equivalent, due to similarities in their chemical structure and spectrum of activity. In recent years, several pertinent differences, especially in terms of potency and disposition, have been revealed between polymyxin B and colistin. These differences are mainly attributed to the fact that polymyxin B is administered parenterally in its active form, while colistin is administered parenterally as an inactive pro-drug, colistimethate. In this review, we summarize the similarities and differences between polymyxin B and colistin. We also discuss the potential clinical implications of these findings, and provide our perspectives on how polymyxins should be employed to preserve their utility in this era of multi-drug resistance.
Financial & competing interests disclosure
AL Kwa has received funding for research from Janssen-Cilag, Pfizer Inc and Merck Sharp & Dohme (I.A) Corp. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Polymyxins – polymyxin B and colistin (polymyxin E) – are last-line therapeutic agents against multi-drug resistant and extensively drug-resistant Gram-negative bacteria.
Recent publications in the past decade have revealed numerous differences in potency and disposition between polymyxin B and colistin, which is formulated in the form of its inactive pro-drug, colistimethate sodium.
In view of the need for in vivo conversion from colistimethate sodium to colistin, colistin appears to have inferior pharmacokinetic properties compared to polymyxin B.
Compared to colistin, there is a lack of clinical experience with polymyxin B.
There is a need to re-evaluate current dosing regimens for colistin and polymyxin B as recent pharmacokinetic studies have suggested that the current regimens recommended by the manufacturers will most likely result in suboptimal drug exposure.
The development of heteroresistance to polymyxins has been increasingly reported against Acinetobacter baumannii and Klebsiella pneumoniae, and limits the utility of polymyxin monotherapy.
Polymyxin combination therapy helps to maximize bacterial killing and prevents development of polymyxin resistance; unfortunately, to date, its clinical advantage is yet to be unequivocally proven.
Nephrotoxicity and neurotoxicity are the most prominent toxicities associated with polymyxins, and incidences appear to be similar or possibly even lesser for polymyxin B than for colistin.