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Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study

BACKGROUND: Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy...

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Autores principales: Tang, Tiantian, Li, Ying, Xu, Ping, Zhong, Yanjun, Yang, Min, Ma, Wanjun, Xiang, Daxiong, Zhang, Bikui, Zhou, Yangang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142183/
https://www.ncbi.nlm.nih.gov/pubmed/37106370
http://dx.doi.org/10.1186/s13054-023-04448-z
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author Tang, Tiantian
Li, Ying
Xu, Ping
Zhong, Yanjun
Yang, Min
Ma, Wanjun
Xiang, Daxiong
Zhang, Bikui
Zhou, Yangang
author_facet Tang, Tiantian
Li, Ying
Xu, Ping
Zhong, Yanjun
Yang, Min
Ma, Wanjun
Xiang, Daxiong
Zhang, Bikui
Zhou, Yangang
author_sort Tang, Tiantian
collection PubMed
description BACKGROUND: Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens. METHODS: Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy. RESULTS: A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUC(ss,24 h)/MIC (AOR = 0.97, 95% CI 0.95–0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97–0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11–0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUC(ss,24 h)/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial. CONCLUSIONS: For CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-023-04448-z.
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spelling pubmed-101421832023-04-29 Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study Tang, Tiantian Li, Ying Xu, Ping Zhong, Yanjun Yang, Min Ma, Wanjun Xiang, Daxiong Zhang, Bikui Zhou, Yangang Crit Care Research BACKGROUND: Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens. METHODS: Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy. RESULTS: A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUC(ss,24 h)/MIC (AOR = 0.97, 95% CI 0.95–0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97–0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11–0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUC(ss,24 h)/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial. CONCLUSIONS: For CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-023-04448-z. BioMed Central 2023-04-28 /pmc/articles/PMC10142183/ /pubmed/37106370 http://dx.doi.org/10.1186/s13054-023-04448-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Tang, Tiantian
Li, Ying
Xu, Ping
Zhong, Yanjun
Yang, Min
Ma, Wanjun
Xiang, Daxiong
Zhang, Bikui
Zhou, Yangang
Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
title Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
title_full Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
title_fullStr Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
title_full_unstemmed Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
title_short Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
title_sort optimization of polymyxin b regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142183/
https://www.ncbi.nlm.nih.gov/pubmed/37106370
http://dx.doi.org/10.1186/s13054-023-04448-z
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