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Critical Care
Published in: Critical Care 1/2023

Open Access 01-12-2023 | Pharmacodynamics | Research

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

Authors: Tiantian Tang, Ying Li, Ping Xu, Yanjun Zhong, Min Yang, Wanjun Ma, Daxiong Xiang, Bikui Zhang, Yangang Zhou

Published in: Critical Care | Issue 1/2023

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Abstract

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. AUCss,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 AUCss,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.
Appendix
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Metadata
Title
Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
Authors
Tiantian Tang
Ying Li
Ping Xu
Yanjun Zhong
Min Yang
Wanjun Ma
Daxiong Xiang
Bikui Zhang
Yangang Zhou
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2023
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-023-04448-z

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