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Published on: April 18, 2019
[Colistin: a review]
Abstract:
Colistin (CS) is a polymyxin with bactericidal activity, which is increasingly used in nosocomial infections associated with multidrug-resistant Gram-negative bacteria (MDR-GNB). Intravenous CS is usually administered as a less toxic pro-drug, i.e. colistin sodium methanesulfonate (CMS). In water-containing solutions, CMS undergoes a spontaneous hydrolysis to form a complex mixture of partially sulfomethylated derivatives and CS. Pharmacokinetic of CS is dependent on the route of administration, i.e. parenteral, intramuscular, nebulized, intrathecal/intraventricular. Renal toxicity is the most common adverse effect of CS treatment, as the drug is excreted primarily by the kidney and elevated levels of CS may further impair renal function, with a dose-dependent effect. Clinical manifestations of CS associated nephrotoxicity include acute kidney injury, proteinuria and tubular damage. Only few data are currently available on the effects of different renal replacement therapy modalities on CS pharmacokinetics. In patients undergoing the most efficient forms of renal replacement therapies, the extracorporeal clearance of CMS may result in a substantial removal of the antibiotic. Thus, in this setting, the recommended daily doses should be increased. Future studies should better explore CS pharmacokinetics in patients undergoing different modalities of renal replacement therapy.
Insights
Colistin (CS) dosing may need adjustment in patients undergoing renal replacement therapy. Efficient kidney support can significantly clear CS, potentially requiring higher doses to maintain effective treatment levels.
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- Colistin (CS) is vital for treating multidrug-resistant Gram-negative bacterial infections.
- Colistin sodium methanesulfonate (CMS) is a pro-drug of CS, hydrolyzing to CS and derivatives in solution.
- CS is primarily renally excreted, and nephrotoxicity is a significant concern.
Purpose of the Study:
- To review the current understanding of colistin pharmacokinetics in patients undergoing renal replacement therapy (RRT).
- To highlight the impact of RRT modalities on CS clearance and dosing recommendations.
Main Methods:
- Literature review focusing on studies investigating CS pharmacokinetics during RRT.
- Analysis of data on CS/CMS removal by different extracorporeal renal replacement therapies.
Main Results:
- Efficient RRT modalities can substantially clear CMS, impacting CS levels.
- Limited data exist on CS pharmacokinetics across various RRT methods.
- Increased CS doses may be necessary in patients on high-efficiency RRT.
Conclusions:
- Colistin dosing requires careful consideration in patients with kidney impairment undergoing RRT.
- Further research is needed to establish optimal CS dosing strategies for different RRT modalities.
- Understanding CS clearance during RRT is crucial for effective and safe treatment of infections.
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