Current opinion in pharmacology
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The increasing prevalence of multidrug-resistant Gram-negative bacteria worldwide has led to a re-evaluation of the previously discarded antibiotic, colistin. Despite its important role as salvage therapy for otherwise untreatable infections, dosage guidelines for the prodrug colistin methanesulfonate (CMS) are not scientifically based and have led to treatment failure and increased colistin resistance. ⋯ The pharmacodynamics of colistin is also reviewed, with special attention given to the relationship between pharmacokinetics and pharmacodynamics and how the emerging data can be used to inform design of optimal dosage regimens. Recent data suggest the current dosage regimens of CMS are suboptimal in many critically ill patients.
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Curr Opin Pharmacol · Oct 2011
ReviewRevisiting Beta-lactams - PK/PD improves dosing of old antibiotics.
Pre-clinical pharmacokinetic-pharmacodynamic assessments indicate Beta-lactam antibiotics have time-dependent killing, variable persistent antibiotic effects and that free drug T>MIC is the dominant pharmacodynamic index. Prolonged or continuous infusion therapy has improved microbiological responses in pathogens with MICs at or 2-4 fold higher than existing EUCAST clinical breakpoints in pre-clinical studies. ⋯ The exception being in various subgroup analyses. Future clinical trials need to focus on defining the T>MIC sizes associated with clinical or microbiological cure in man, on those subgroups of patients where continuous, or prolonged infusion, is likely to be of greatest benefit, seek to reduce pharmacokinetic variability by the use of therapeutic drug monitoring and include measurement of the risks of emergence of resistance in target pathogens At present, the clinical evidence base for prolonged or continuous infusion therapy is insufficiently strong to support widespread use.