Abstract
(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.
Highlights
Multidrug resistant pathogens (MDR) and extensively drug resistant pathogens (XDR) are posing an imminent threat on the clinicians’ ability to battle infections
We present our findings on Therapeutic Drug Monitoring (TDM) of colisthimethate sodium (CMS) and Colistin in critically ill patients suffering from MDR Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa infection
In five patients TDM was initiated at the start, for the remaining patients TDM started during ongoing CMS treatment as indicated
Summary
Multidrug resistant pathogens (MDR) and extensively drug resistant pathogens (XDR) are posing an imminent threat on the clinicians’ ability to battle infections. The growing rate of pathogens resistant to all of the four main antibiotic classes (Pan-drug resistant, PDR) severely limits available options for treatment [2]. Infections with these pathogens lead to an exceptionally high mortality rate in septic patients [3,4]. With this burden, clinicians are forced to resort to older substances such as polymyxin B or polymyxin E/Colistin [5]. Colistin provides a treatment option for otherwise resistant gram-negative strains, especially Pseudomonas aeruginosa, Klebsiella species and Acinetobacter species [6]
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