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In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae
OBJECTIVES: Colistin is still a “last-resort” antibiotic used to manage human infections due to multidrug-resistant (MDR) Klebsiella pneumoniae. However, colistin-resistant K. pneumoniae (CR-Kp) isolates emerged a decade ago and had a worldwide distribution. The purpose of this study was to evaluate...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926077/ https://www.ncbi.nlm.nih.gov/pubmed/29731646 http://dx.doi.org/10.2147/IDR.S160474 |
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author | Yu, Wei Luo, Qixia Shi, Qingyi Huang, Chen Yu, Xiao Niu, Tianshui Zhou, Kai Zhang, Jiajie Xiao, Yonghong |
author_facet | Yu, Wei Luo, Qixia Shi, Qingyi Huang, Chen Yu, Xiao Niu, Tianshui Zhou, Kai Zhang, Jiajie Xiao, Yonghong |
author_sort | Yu, Wei |
collection | PubMed |
description | OBJECTIVES: Colistin is still a “last-resort” antibiotic used to manage human infections due to multidrug-resistant (MDR) Klebsiella pneumoniae. However, colistin-resistant K. pneumoniae (CR-Kp) isolates emerged a decade ago and had a worldwide distribution. The purpose of this study was to evaluate the genetic data of CR-Kp and identify the antibacterial activity of fosfomycin (FM) alone and in combination with amikacin (AMK) or colistin (COL) against CR-Kp in vitro. METHODS: Three clinical CR-Kp isolates from three patients were collected. Whole-genome sequencing and bioinformatics analysis were performed. The Pharmacokinetics Auto Simulation System 400, by simulating human pharmacokinetics in vitro, was employed to simulate FM, AMK, and COL alone and in combination. Different pharmacodynamic parameters were calculated for determining the antimicrobial effect. RESULTS: Whole-genome sequencing revealed that none of the three isolates contain mcr gene and that no insertion was found in pmrAB, phoPQ, or mgrB genes. We found the antibacterial activity of AMK alone was more efficient than FM or COL against CR-Kp. The area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was higher than 170 LogCFU/mL·h(−1). In addition, the area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with COL (75,000 IU/kg every12 hours) was higher than that of monotherapies (>100 LogCFU/mL·h(−1) vs <80 LogCFU/mL·h(−1)). CONCLUSION: FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was effective at maximizing bacterial killing against CR-Kp. |
format | Online Article Text |
id | pubmed-5926077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59260772018-05-04 In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae Yu, Wei Luo, Qixia Shi, Qingyi Huang, Chen Yu, Xiao Niu, Tianshui Zhou, Kai Zhang, Jiajie Xiao, Yonghong Infect Drug Resist Original Research OBJECTIVES: Colistin is still a “last-resort” antibiotic used to manage human infections due to multidrug-resistant (MDR) Klebsiella pneumoniae. However, colistin-resistant K. pneumoniae (CR-Kp) isolates emerged a decade ago and had a worldwide distribution. The purpose of this study was to evaluate the genetic data of CR-Kp and identify the antibacterial activity of fosfomycin (FM) alone and in combination with amikacin (AMK) or colistin (COL) against CR-Kp in vitro. METHODS: Three clinical CR-Kp isolates from three patients were collected. Whole-genome sequencing and bioinformatics analysis were performed. The Pharmacokinetics Auto Simulation System 400, by simulating human pharmacokinetics in vitro, was employed to simulate FM, AMK, and COL alone and in combination. Different pharmacodynamic parameters were calculated for determining the antimicrobial effect. RESULTS: Whole-genome sequencing revealed that none of the three isolates contain mcr gene and that no insertion was found in pmrAB, phoPQ, or mgrB genes. We found the antibacterial activity of AMK alone was more efficient than FM or COL against CR-Kp. The area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was higher than 170 LogCFU/mL·h(−1). In addition, the area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with COL (75,000 IU/kg every12 hours) was higher than that of monotherapies (>100 LogCFU/mL·h(−1) vs <80 LogCFU/mL·h(−1)). CONCLUSION: FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was effective at maximizing bacterial killing against CR-Kp. Dove Medical Press 2018-04-24 /pmc/articles/PMC5926077/ /pubmed/29731646 http://dx.doi.org/10.2147/IDR.S160474 Text en © 2018 Yu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Yu, Wei Luo, Qixia Shi, Qingyi Huang, Chen Yu, Xiao Niu, Tianshui Zhou, Kai Zhang, Jiajie Xiao, Yonghong In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae |
title | In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae |
title_full | In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae |
title_fullStr | In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae |
title_full_unstemmed | In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae |
title_short | In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae |
title_sort | in vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant klebsiella pneumoniae |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926077/ https://www.ncbi.nlm.nih.gov/pubmed/29731646 http://dx.doi.org/10.2147/IDR.S160474 |
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