Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study
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 e...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Critical Care |
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| Online Access: | https://doi.org/10.1186/s13054-023-04448-z |
| _version_ | 1797836415107596288 |
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| author | Tiantian Tang Ying Li Ping Xu Yanjun Zhong Min Yang Wanjun Ma Daxiong Xiang Bikui Zhang Yangang Zhou |
| author_facet | Tiantian Tang Ying Li Ping Xu Yanjun Zhong Min Yang Wanjun Ma Daxiong Xiang Bikui Zhang Yangang Zhou |
| author_sort | Tiantian Tang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:09:17Z |
| format | Article |
| id | doaj.art-663ca34b39bc4ba48c1d808bf218582f |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-04-09T15:09:17Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-663ca34b39bc4ba48c1d808bf218582f2023-04-30T11:17:49ZengBMCCritical Care1364-85352023-04-0127111210.1186/s13054-023-04448-zOptimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective studyTiantian Tang0Ying Li1Ping Xu2Yanjun Zhong3Min Yang4Wanjun Ma5Daxiong Xiang6Bikui Zhang7Yangang Zhou8Department of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Critical Care Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityAbstract 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.https://doi.org/10.1186/s13054-023-04448-zPolymyxin BCarbapenem-resistant organismNosocomial pneumoniaDosing optimizationPharmacokinetic/pharmacodynamic |
| spellingShingle | Tiantian Tang Ying Li Ping Xu Yanjun Zhong Min Yang Wanjun Ma Daxiong Xiang Bikui Zhang Yangang Zhou Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study Critical Care Polymyxin B Carbapenem-resistant organism Nosocomial pneumonia Dosing optimization Pharmacokinetic/pharmacodynamic |
| 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 | Polymyxin B Carbapenem-resistant organism Nosocomial pneumonia Dosing optimization Pharmacokinetic/pharmacodynamic |
| url | https://doi.org/10.1186/s13054-023-04448-z |
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