Polymyxin pharmacokinetics and pharmacodynamics

Soon-Ee Cheah, Jian Li, Phillip John Bergen, Roger Leigh Nation

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

Abstract

Polymyxin B and E (the latter more commonly known as colistin) were originally introduced into clinicalmedicine in the late 1950s for the treatment of infections caused by gram-negative pathogens. They fellinto relative disuse during the next decade as concern about their potential to cause nephrotoxicity grewand other new antibiotics regarded at the time as less toxic became available. In more recent times, thepolymyxins have been resurrected as an important component of the therapeutic armamentarium becauseof rising rates of resistance to other available antibiotics and the limited number of new antibacterial agentswith activity against gram-negative pathogens emerging from the drug development pipeline. At the timeof their original regulatory approval for clinical use the rigor of drug development and approval processeswas substantially less than it is today and there was little information to guide clinicians in the optimal useof these agents. Over the last decade, the polymyxins have been subject to a “redevelopment” process, ledby academic researchers and clinicians, and funded largely by public grant bodies around the world. Theresult has been a considerable increase in knowledge of the preclinical and clinical pharmacology of thepolymyxins. This chapter reviews key aspects of the chemistry, microbiology, and especially the pharmacokineticsand pharmacodynamics of both of the clinically available polymyxins. The similarities and differencesbetween colistin and polymyxin B are highlighted as are the clinical implications for use of theseimportant last-line antibiotics.
Original languageEnglish
Title of host publicationAntibiotic Pharmacodynamics
EditorsJohn C Rotschafer, David R Andes, Keith A Rodvold
Place of PublicationNew York NY USA
PublisherSpringer
Pages221-260
Number of pages39
ISBN (Electronic)9781493933235
ISBN (Print)9781493933211
DOIs
Publication statusPublished - 2016

Publication series

NameMethods in Pharmacology and Toxicology
PublisherSpringer
ISSN (Print)1557-2153
ISSN (Electronic)1940-6053

Keywords

  • A. baumannii
  • Colistin
  • Colistin methanesulfonate
  • Dose optimization
  • K. pneumoniae
  • Multidrug resistance
  • P. aeruginosa
  • Pharmacodynamics
  • Pharmacokinetics
  • Polymyxin B

Cite this

Cheah, S-E., Li, J., Bergen, P. J., & Nation, R. L. (2016). Polymyxin pharmacokinetics and pharmacodynamics. In J. C. Rotschafer, D. R. Andes, & K. A. Rodvold (Eds.), Antibiotic Pharmacodynamics (pp. 221-260). (Methods in Pharmacology and Toxicology). New York NY USA: Springer. https://doi.org/10.1007/978-1-4939-3323-5_10
Cheah, Soon-Ee ; Li, Jian ; Bergen, Phillip John ; Nation, Roger Leigh. / Polymyxin pharmacokinetics and pharmacodynamics. Antibiotic Pharmacodynamics. editor / John C Rotschafer ; David R Andes ; Keith A Rodvold. New York NY USA : Springer, 2016. pp. 221-260 (Methods in Pharmacology and Toxicology).
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Cheah, S-E, Li, J, Bergen, PJ & Nation, RL 2016, Polymyxin pharmacokinetics and pharmacodynamics. in JC Rotschafer, DR Andes & KA Rodvold (eds), Antibiotic Pharmacodynamics. Methods in Pharmacology and Toxicology, Springer, New York NY USA, pp. 221-260. https://doi.org/10.1007/978-1-4939-3323-5_10

Polymyxin pharmacokinetics and pharmacodynamics. / Cheah, Soon-Ee; Li, Jian; Bergen, Phillip John; Nation, Roger Leigh.

Antibiotic Pharmacodynamics. ed. / John C Rotschafer; David R Andes; Keith A Rodvold. New York NY USA : Springer, 2016. p. 221-260 (Methods in Pharmacology and Toxicology).

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

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T1 - Polymyxin pharmacokinetics and pharmacodynamics

AU - Cheah, Soon-Ee

AU - Li, Jian

AU - Bergen, Phillip John

AU - Nation, Roger Leigh

PY - 2016

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N2 - Polymyxin B and E (the latter more commonly known as colistin) were originally introduced into clinicalmedicine in the late 1950s for the treatment of infections caused by gram-negative pathogens. They fellinto relative disuse during the next decade as concern about their potential to cause nephrotoxicity grewand other new antibiotics regarded at the time as less toxic became available. In more recent times, thepolymyxins have been resurrected as an important component of the therapeutic armamentarium becauseof rising rates of resistance to other available antibiotics and the limited number of new antibacterial agentswith activity against gram-negative pathogens emerging from the drug development pipeline. At the timeof their original regulatory approval for clinical use the rigor of drug development and approval processeswas substantially less than it is today and there was little information to guide clinicians in the optimal useof these agents. Over the last decade, the polymyxins have been subject to a “redevelopment” process, ledby academic researchers and clinicians, and funded largely by public grant bodies around the world. Theresult has been a considerable increase in knowledge of the preclinical and clinical pharmacology of thepolymyxins. This chapter reviews key aspects of the chemistry, microbiology, and especially the pharmacokineticsand pharmacodynamics of both of the clinically available polymyxins. The similarities and differencesbetween colistin and polymyxin B are highlighted as are the clinical implications for use of theseimportant last-line antibiotics.

AB - Polymyxin B and E (the latter more commonly known as colistin) were originally introduced into clinicalmedicine in the late 1950s for the treatment of infections caused by gram-negative pathogens. They fellinto relative disuse during the next decade as concern about their potential to cause nephrotoxicity grewand other new antibiotics regarded at the time as less toxic became available. In more recent times, thepolymyxins have been resurrected as an important component of the therapeutic armamentarium becauseof rising rates of resistance to other available antibiotics and the limited number of new antibacterial agentswith activity against gram-negative pathogens emerging from the drug development pipeline. At the timeof their original regulatory approval for clinical use the rigor of drug development and approval processeswas substantially less than it is today and there was little information to guide clinicians in the optimal useof these agents. Over the last decade, the polymyxins have been subject to a “redevelopment” process, ledby academic researchers and clinicians, and funded largely by public grant bodies around the world. Theresult has been a considerable increase in knowledge of the preclinical and clinical pharmacology of thepolymyxins. This chapter reviews key aspects of the chemistry, microbiology, and especially the pharmacokineticsand pharmacodynamics of both of the clinically available polymyxins. The similarities and differencesbetween colistin and polymyxin B are highlighted as are the clinical implications for use of theseimportant last-line antibiotics.

KW - A. baumannii

KW - Colistin

KW - Colistin methanesulfonate

KW - Dose optimization

KW - K. pneumoniae

KW - Multidrug resistance

KW - P. aeruginosa

KW - Pharmacodynamics

KW - Pharmacokinetics

KW - Polymyxin B

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U2 - 10.1007/978-1-4939-3323-5_10

DO - 10.1007/978-1-4939-3323-5_10

M3 - Chapter (Book)

SN - 9781493933211

T3 - Methods in Pharmacology and Toxicology

SP - 221

EP - 260

BT - Antibiotic Pharmacodynamics

A2 - Rotschafer, John C

A2 - Andes, David R

A2 - Rodvold, Keith A

PB - Springer

CY - New York NY USA

ER -

Cheah S-E, Li J, Bergen PJ, Nation RL. Polymyxin pharmacokinetics and pharmacodynamics. In Rotschafer JC, Andes DR, Rodvold KA, editors, Antibiotic Pharmacodynamics. New York NY USA: Springer. 2016. p. 221-260. (Methods in Pharmacology and Toxicology). https://doi.org/10.1007/978-1-4939-3323-5_10