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Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection

Polymyxin B has been used as a last-line therapy for the treatment of carbapenem-resistant gram-negative bacterial infection. The pharmacokinetic/pharmacodynamic index (AUC/MIC) of polymyxin B has not been clinically evaluated, given that the broth microdilution method for polymyxin susceptibility t...

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Autores principales: Wang, Peile, Liu, Shaohua, Qi, Guangzhao, Xu, Min, Sun, Tongwen, Yang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10477696/
https://www.ncbi.nlm.nih.gov/pubmed/37675417
http://dx.doi.org/10.3389/fmicb.2023.1226981
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author Wang, Peile
Liu, Shaohua
Qi, Guangzhao
Xu, Min
Sun, Tongwen
Yang, Jing
author_facet Wang, Peile
Liu, Shaohua
Qi, Guangzhao
Xu, Min
Sun, Tongwen
Yang, Jing
author_sort Wang, Peile
collection PubMed
description Polymyxin B has been used as a last-line therapy for the treatment of carbapenem-resistant gram-negative bacterial infection. The pharmacokinetic/pharmacodynamic index (AUC/MIC) of polymyxin B has not been clinically evaluated, given that the broth microdilution method for polymyxin susceptibility testing is rarely used in hospitals. This study analyzed data from 77 patients with carbapenem-resistant Klebsiella pneumoniae infections. Among the samples, 63 K. pneumoniae isolates had MIC values of 1.0 mg/L as measured by broth microdilution but 0.5 mg/L as measured using the Vitek 2 system. Polymyxin B AUC/MIC was significantly associated with clinical response (p = 0.002) but not with 30-day all-cause mortality (p = 0.054). With a target AUC/MIC value of 50, Monte Carlo simulations showed that a fixed dose of 100 mg/12 h and three weight-based regimens (1.25 mg/kg/12 h for 80 kg and 1.5 mg/kg/12 h for 70 kg/80 kg) achieved a cumulative fraction of response >90% regardless of renal function, but the risk of nephrotoxicity was high. For patients with carbapenem-resistant K. pneumoniae infections, the underestimation of polymyxin resistance in automated systems need to be taken into account when optimizing polymyxin B dosing based on pharmacokinetic/pharmacodynamic principles.
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spelling pubmed-104776962023-09-06 Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection Wang, Peile Liu, Shaohua Qi, Guangzhao Xu, Min Sun, Tongwen Yang, Jing Front Microbiol Microbiology Polymyxin B has been used as a last-line therapy for the treatment of carbapenem-resistant gram-negative bacterial infection. The pharmacokinetic/pharmacodynamic index (AUC/MIC) of polymyxin B has not been clinically evaluated, given that the broth microdilution method for polymyxin susceptibility testing is rarely used in hospitals. This study analyzed data from 77 patients with carbapenem-resistant Klebsiella pneumoniae infections. Among the samples, 63 K. pneumoniae isolates had MIC values of 1.0 mg/L as measured by broth microdilution but 0.5 mg/L as measured using the Vitek 2 system. Polymyxin B AUC/MIC was significantly associated with clinical response (p = 0.002) but not with 30-day all-cause mortality (p = 0.054). With a target AUC/MIC value of 50, Monte Carlo simulations showed that a fixed dose of 100 mg/12 h and three weight-based regimens (1.25 mg/kg/12 h for 80 kg and 1.5 mg/kg/12 h for 70 kg/80 kg) achieved a cumulative fraction of response >90% regardless of renal function, but the risk of nephrotoxicity was high. For patients with carbapenem-resistant K. pneumoniae infections, the underestimation of polymyxin resistance in automated systems need to be taken into account when optimizing polymyxin B dosing based on pharmacokinetic/pharmacodynamic principles. Frontiers Media S.A. 2023-08-22 /pmc/articles/PMC10477696/ /pubmed/37675417 http://dx.doi.org/10.3389/fmicb.2023.1226981 Text en Copyright © 2023 Wang, Liu, Qi, Xu, Sun and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Wang, Peile
Liu, Shaohua
Qi, Guangzhao
Xu, Min
Sun, Tongwen
Yang, Jing
Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection
title Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection
title_full Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection
title_fullStr Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection
title_full_unstemmed Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection
title_short Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection
title_sort evaluation of polymyxin b auc/mic ratio for dose optimization in patients with carbapenem-resistant klebsiella pneumoniae infection
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10477696/
https://www.ncbi.nlm.nih.gov/pubmed/37675417
http://dx.doi.org/10.3389/fmicb.2023.1226981
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