Colistin

Colistin is a revived old drug to treat extensively drug resistant Gram-negative bacteria such as carbapenemase producing enterobacteriaceae, Acinetobacter, or Pseudomonas aeruginosa.

Colistin – a mixture of cationic polypeptides from the group of polymyxin antibiotics – was discovered in 1949 and first used as an intravenous formulation in the 1950s. In the early 1980’s, colistin use was largely abandoned due to reported nephrotoxicity and the availability of newer antibiotics. Colistin was never subject to regulations in a modern kind of way and systematic trials on pharmacokinetics and dose finding are just beginning to be conducted. Through all these years colistin has been used in Cystic Fibrosis as inhalative treatment adjunct and in various topical formulations. The optimal parenteral dosing of colistin in severely ill patients is largely unknown and not standardized. This uncertainty and absence of any regulation or standardisation of dose puts a high burden on physicians and unacceptable risk on patients. Additionally, inadequate usage favors resistance development and threatens colistin’s life span.

For more basic information see the fact sheet, literature overview, and extensive background information on the website of the European FP7 funded project AIDA (PRESERVING OLD ANTIBIOTICS FOR THE FUTURE)

Reviving of colistin led to an improved understanding of its chemistry, pharmacokinetics and pharmacodynamics, enabling important steps towards optimizing its clinical use in different patient populations. Current study results suggest a loading dose to achieve active colistin concentrations after the administration of the inactive prodrug colistimethate sodium (CMS) quickly and a maintenance dosing regimen that is based on the patient’s kidney function. According to predictions from PK/PD models and preliminary clinical results the dosing regimen of CMS for patients with normal weight and kidney function is a 9 Mill. IU loading dose and 4.5 Mill. IU q12h or 3 Mill. IU q8h maintenance dose.

Worldwide the recommended dosages in the approved Summary of Product Characteristics (SPCs) vary considerably according to the country and supplier.  Accordingly, physicians often use dosage regimens that differ in the amount of the single dose as well as the dosing interval. In Europe, colistin has not been subject to the European centralized approval or any harmonisation procedure. Therefore, the SPCs are still reflecting old and wrong information in some European countries. Using inappropriate dosage regimens may not only risk clinical failure but also fast development of resistance as the active colistin concentrations might be much lower than previously thought.

For the first time, this website provides information across Europe that enables the comparison of approved dosing recommendations in different patient populations as well as indications based on the current version of SPCs that have been translated to English.

More information on colistin:

Prato Consensus 2013
Pharmacokinetics
PK/PD
Dosing
Approved dosing recommendations in European countries
Resistance
Breakpoints
Regulatory issues in Europe
Dosing terminology
Composition

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