Urinary bactericidal activity of colistin and azidothymidine combinations against mcr-1-positive colistin-resistant Escherichia coli
| Autor: | Maria Loose, Kurt G. Naber, Yanmin Hu, Anthony Coates, Florian M.E. Wagenlehner |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Microbiology (medical)
Microbial Viability Acinetobacter Colistin Escherichia coli Proteins Drug Synergism General Medicine Urine biochemical phenomena metabolism and nutrition bacterial infections and mycoses Anti-Bacterial Agents Infectious Diseases Pseudomonas Escherichia coli Humans Drug Therapy Combination Pharmacology (medical) lipids (amino acids peptides and proteins) Zidovudine |
| ISSN: | 1872-7913 |
| Popis: | A phase 1 clinical study was performed to assess the pharmacokinetics and safety of intravenous (i.v.) administration of colistin methanesulfonate (CMS) and azidothymidine (AZT) alone and in combination. Seven healthy subjects received three (every 12 h) 1-h i.v. infusions of 4, 2 and 2 million international units (MIU) of CMS co-administered with 200, 100 and 100 mg of AZT, respectively. In an ex vivo study, urinary bactericidal titres (UBTs) and time-kill curve determinations were performed in artificial urine spiked with colistin sulfate and AZT according to median and minimum peak concentrations in urine measured after the first and third dose using four mcr-1-positive colistin-resistant and five colistin-susceptible Gram-negative isolates. Reciprocal UBTs for the different colistin concentrations obtained in urine ranged from 1-128 and 0-2 for colistin-susceptible and colistin-resistant isolates, respectively. Combination with AZT could increase UBTs up to two dilution steps each for the Enterobacteriaceae and Acinetobacter strains tested. In contrast, the combination had no activity against Pseudomonas strains. In time-kill curves, the combination showed bactericidal activity against colistin-resistant strains even when the substances alone were not bactericidal. Thus, combination of CMS with AZT shows promising synergistic activity against Gram-negative uropathogens, including colistin-resistant Enterobacteriaceae. According to the urinary bactericidal activity, a maintenance dosage of 2 MIU of CMS combined with 100 mg of AZT twice daily may be sufficient for the treatment of urinary tract infections (UTIs) caused by colistin-susceptible strains. However, the dosage requires optimisation for efficient treatment of UTIs caused by colistin-resistant strains. |
| Databáze: | OpenAIRE |
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