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Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model
Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the greatest threats to public health, and combination therapy may be the chemotherapeutic option. In the present study, we aimed to evaluate the antibacterial effects of colistin/fosfomycin combination against carbapenem...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937563/ https://www.ncbi.nlm.nih.gov/pubmed/29850537 http://dx.doi.org/10.1155/2018/5720417 |
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author | Wang, Jin He, Ji-tong Bai, Yan Wang, Rui Cai, Yun |
author_facet | Wang, Jin He, Ji-tong Bai, Yan Wang, Rui Cai, Yun |
author_sort | Wang, Jin |
collection | PubMed |
description | Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the greatest threats to public health, and combination therapy may be the chemotherapeutic option. In the present study, we aimed to evaluate the antibacterial effects of colistin/fosfomycin combination against carbapenemase-producing K. pneumoniae. The antibacterial effects were determined in a one-compartment in vitro pharmacokinetic model over a period of 24 h. The initial inoculum was 10(8) CFU/mL. Low, medium, and high C(max) values of colistin at 0.5, 2, and 5 mg/L as well as C(max) of fosfomycin at 100 mg/L were simulated in the model. Doses of both colistin and fosfomycin were given every 8 h until 24 h. For the colistin- and fosfomycin-susceptible isolate KP47, three combination regimens showed greater killing effect compared with colistin monotherapy. The greatest killing effect was observed in combination regimen containing 5 mg/L colistin. For colistin-heteroresistant and fosfomycin-susceptible isolate KP79, combination regimen containing low dose colistin (0.5 mg/L) showed no synergistic or additive effects. However, combination regimens containing 2 and 5 mg/L colistin maintained the bactericidal effect until 24 h compared with colistin monotherapy. For colistin-heteroresistant and fosfomycin-resistant isolates KP42 and KP11, bactericidal activity was barely enhanced by combination regimens. Moreover, combination regimen containing 5 mg/L colistin could only prevent the emergence of colistin-resistant subpopulation in colistin and fosfomycin-susceptible isolate. It is necessary to know the resistant patterns of the K. pneumoniae before using combination of colistin and fosfomycin in clinical practice. |
format | Online Article Text |
id | pubmed-5937563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-59375632018-05-30 Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model Wang, Jin He, Ji-tong Bai, Yan Wang, Rui Cai, Yun Biomed Res Int Research Article Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the greatest threats to public health, and combination therapy may be the chemotherapeutic option. In the present study, we aimed to evaluate the antibacterial effects of colistin/fosfomycin combination against carbapenemase-producing K. pneumoniae. The antibacterial effects were determined in a one-compartment in vitro pharmacokinetic model over a period of 24 h. The initial inoculum was 10(8) CFU/mL. Low, medium, and high C(max) values of colistin at 0.5, 2, and 5 mg/L as well as C(max) of fosfomycin at 100 mg/L were simulated in the model. Doses of both colistin and fosfomycin were given every 8 h until 24 h. For the colistin- and fosfomycin-susceptible isolate KP47, three combination regimens showed greater killing effect compared with colistin monotherapy. The greatest killing effect was observed in combination regimen containing 5 mg/L colistin. For colistin-heteroresistant and fosfomycin-susceptible isolate KP79, combination regimen containing low dose colistin (0.5 mg/L) showed no synergistic or additive effects. However, combination regimens containing 2 and 5 mg/L colistin maintained the bactericidal effect until 24 h compared with colistin monotherapy. For colistin-heteroresistant and fosfomycin-resistant isolates KP42 and KP11, bactericidal activity was barely enhanced by combination regimens. Moreover, combination regimen containing 5 mg/L colistin could only prevent the emergence of colistin-resistant subpopulation in colistin and fosfomycin-susceptible isolate. It is necessary to know the resistant patterns of the K. pneumoniae before using combination of colistin and fosfomycin in clinical practice. Hindawi 2018-04-23 /pmc/articles/PMC5937563/ /pubmed/29850537 http://dx.doi.org/10.1155/2018/5720417 Text en Copyright © 2018 Jin Wang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Jin He, Ji-tong Bai, Yan Wang, Rui Cai, Yun Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model |
title | Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model |
title_full | Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model |
title_fullStr | Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model |
title_full_unstemmed | Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model |
title_short | Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model |
title_sort | synergistic activity of colistin/fosfomycin combination against carbapenemase-producing klebsiella pneumoniae in an in vitro pharmacokinetic/pharmacodynamic model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937563/ https://www.ncbi.nlm.nih.gov/pubmed/29850537 http://dx.doi.org/10.1155/2018/5720417 |
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