Colistin an update on the antibiotic

clinical aspects PK/PD indices and equivalences

Abstract

In the recent 10 years, in this post-antibiotic era, colisitin has reappeared as the last resource to face infections caused by Pseudomonas aeruginosa, Acinetobacter baumannii complex and carbapenemase-producing enterobacteriaceae. At some point the use of colistin was discontinued given its potentially severe side effects, such as nephro and neurotoxicity , although it reemerges today as an essential part of antibiotic plans when facing extremely resistant pathogens. This increase in the use of colistin has led to an antibiotic resistance emergency and thus today we face a potentially catastrophic situation. This happens in particular in connection with the recently described presence of transferable plasmids among species containing genes that confer resistance to colistin (gen mcr-1), a mechanism also identified in our country. This review describes in detail the right dosing with the need to make load doses to achieve the appropriate therapeutic levels, based on current knowledge on pharmacokinetics and pharmacodynamics, as well as practical aspects in the administration of the drug in cases of postsurgical meningitis/ventriculitis and the use by nebulization for the treatment of ventilation associated pneumonia. The study points out the need to use colistin along with another in-vitro active antibiotic, especially in critical patients and those with a creatinine clearance over 80 ml/min. Dual pharmacotherapy is necessary in particular if the pathogen´s minimuminhibitory concentration (MIC) is higher than 1 mg/min, due to intra-treatment risk of sub-dosing and resistance emergency. Likewise, in second section, the study addresses the complex nature of dosing given by the different presentations available in the market at the national level, what has resulted in dosage errors, and thus a higher risk of toxicity. The insets and primary packaging of colistin presentation available in the Uruguayan marketing were reviewed with the purpose of improving understanding in connection with the labeling of the doses to be administered. With that information, the pharmaceutical industries agents will be formally asked in writing to inform the colistin content (active drug) and its prodrug colistimethate sodium. Last, a number of recommendations were prepared as to the Information the authors understand should appear in the different presentations of colistin that is available in the market, to avoid prescription errors.