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Serum bactericidal activity of three different dosing regimens of colistin with implications for optimum clinical use

G L Daikos1, A Skiada, J Pavleas

  • 1First Department of Propaedeutic Medicine, University of Athens, Athens, Greece. gdaikos@med.uoa.gr

Journal of Chemotherapy (Florence, Italy)
|June 23, 2010
PubMed

Insights

Optimizing colistin methanesulfonate (CMS) dosing is crucial for treating multidrug-resistant infections. Higher CMS doses at longer intervals may enhance bacterial killing against Pseudomonas aeruginosa.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Colistin methanesulfonate (CMS) is vital for treating multidrug-resistant organism infections in critically ill patients.
  • Current CMS dosing regimens require optimization for maximum therapeutic efficacy.

Purpose of the Study:

  • To evaluate the pharmacokinetics of three distinct CMS dosing regimens.
  • To assess the in vitro bactericidal activity of colistin against Pseudomonas aeruginosa.

Main Methods:

  • Examined three CMS dosing regimens: 3 million units every 8h, 4.5 million units every 12h, and 9 million units every 24h.
  • Assessed serum colistin concentrations (Cmax) and bactericidal activity against P. aeruginosa (MIC 1 microg/ml).

Main Results:

  • Serum Cmax values were 3.34+/-0.35, 2.98+/-0.27, and 5.63+/-0.87 microg/ml for the respective regimens.
  • Colistin concentrations >4 microg/ml (serum concentration/MIC >4) achieved complete bacterial killing.
  • Concentrations <4 microg/ml resulted in only 40% complete bacterial killing.

Conclusions:

  • Current CMS dosing regimens may not ensure optimal therapeutic outcomes.
  • Administering larger CMS dosages at less frequent intervals warrants further investigation for improved efficacy.

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