Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial Emulation

Abstract Introduction Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited, with polymyxin B (PMB) and ceftazidime-avibactam (CZA) being among the available choices. However, research on these options is scarce and significantly heterogeneous. This study aims to...

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Main Authors: Na Hu, Fengjiao Xiao, Yechao Chen, Qiaoling Gu, Pei Liang, Yin Xu, Jinchun Liu, Yunxing Liu, Yi-chen Li, Yinqiu Xu, Mengyin Liu, Dayu Chen, Haixia Zhang
Format: Article
Language:English
Published: Adis, Springer Healthcare 2025-05-01
Series:Infectious Diseases and Therapy
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Online Access:https://doi.org/10.1007/s40121-025-01164-9
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author Na Hu
Fengjiao Xiao
Yechao Chen
Qiaoling Gu
Pei Liang
Yin Xu
Jinchun Liu
Yunxing Liu
Yi-chen Li
Yinqiu Xu
Mengyin Liu
Dayu Chen
Haixia Zhang
author_facet Na Hu
Fengjiao Xiao
Yechao Chen
Qiaoling Gu
Pei Liang
Yin Xu
Jinchun Liu
Yunxing Liu
Yi-chen Li
Yinqiu Xu
Mengyin Liu
Dayu Chen
Haixia Zhang
author_sort Na Hu
collection DOAJ
description Abstract Introduction Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited, with polymyxin B (PMB) and ceftazidime-avibactam (CZA) being among the available choices. However, research on these options is scarce and significantly heterogeneous. This study aims to analyze the efficacy, safety, and cost-effectiveness of PMB and CZA within a standardized target trial emulation (TTE) framework. Methods This retrospective study emulated a target trial to evaluate the efficacy, safety, and cost-effectiveness of CZA versus PMB for treating CRE infections. Conducted at Nanjing Drum Tower Hospital, this study included adult patients treated with CZA or PMB from July 2020 to December 2022. Data on demographics, treatment outcomes, and costs were collected. The primary outcomes included clinical cure, incidence of adverse drug reactions (ADRs), and cost-effectiveness. Secondary outcomes assessed 28-day all-cause mortality, microbiological eradication rates, incidence of acute kidney injury (AKI), and gastrointestinal events. The outcomes were assessed using the modified intention-to-treat (mITT) effects, per-protocol effects, and propensity score overlap weighting (PSOW) methods. Results Between July 1, 2020, and December 31, 2022, 492 hospitalized patients treated with CZA or PMB were screened at Nanjing Drum Tower Hospital. Following inclusion and exclusion criteria, 176 patients were included in the mITT analysis, and 153 in the per-protocol analysis. The clinical cure rate was significantly higher in the CZA group compared to the PMB group across all analyses. The 28-day mortality was similar between groups, while the microbial eradication rate was significantly higher in the CZA group compared to the PMB group across all analyses. The incidence of ADRs was consistent between groups, but AKI occurred more frequently in PMB patients, while gastrointestinal events were more common in the CZA group. The CZA strategy demonstrated a 28.1% increase in efficacy, with an incremental cost-effectiveness ratio of 71,651.76 yuan. Sensitivity analyses confirmed the robustness of these findings. Conclusions This study demonstrates that CZA has a higher clinical cure rate compared to PMB within a standard TTE framework. However, the overall incidence of ADRs was similar between the two treatments. Pharmacoeconomic analysis also indicated that CZA is cost-effective. Trial registration https://www.chictr.org.cn ; identifier, ChiCTR2300067946.
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spelling doaj-art-ffe186db91e94e5a8c57ec40a8b11a992025-08-20T04:03:00ZengAdis, Springer HealthcareInfectious Diseases and Therapy2193-82292193-63822025-05-011471419143710.1007/s40121-025-01164-9Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial EmulationNa Hu0Fengjiao Xiao1Yechao Chen2Qiaoling Gu3Pei Liang4Yin Xu5Jinchun Liu6Yunxing Liu7Yi-chen Li8Yinqiu Xu9Mengyin Liu10Dayu Chen11Haixia Zhang12Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing University of Chinese MedicineDepartment of Pharmacy, Anyang Tumor Hospital, The Affiliated Anyang Tumor Hospital of Henan University of Science and TechnologyDepartment of Pharmacy, Nanjing Drum Tower Hospital, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical UniversityDepartment of Pharmacy, Nanjing Drum Tower Hospital, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical UniversityDepartment of Pharmacy, Nanjing Drum Tower HospitalIntensive Care Unit, Nanjing Drum Tower HospitalDepartment of Pharmacy, Nanjing Drum Tower HospitalDepartment of Pharmacy, Nanjing Drum Tower HospitalDepartment of Pharmacy, Nanjing Drum Tower HospitalDepartment of Pharmacy, Nanjing Drum Tower HospitalDepartment of Pharmacy, Nanjing Drum Tower HospitalDepartment of Pharmacy, Nanjing Drum Tower HospitalDepartment of Pharmacy, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing University of Chinese MedicineAbstract Introduction Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited, with polymyxin B (PMB) and ceftazidime-avibactam (CZA) being among the available choices. However, research on these options is scarce and significantly heterogeneous. This study aims to analyze the efficacy, safety, and cost-effectiveness of PMB and CZA within a standardized target trial emulation (TTE) framework. Methods This retrospective study emulated a target trial to evaluate the efficacy, safety, and cost-effectiveness of CZA versus PMB for treating CRE infections. Conducted at Nanjing Drum Tower Hospital, this study included adult patients treated with CZA or PMB from July 2020 to December 2022. Data on demographics, treatment outcomes, and costs were collected. The primary outcomes included clinical cure, incidence of adverse drug reactions (ADRs), and cost-effectiveness. Secondary outcomes assessed 28-day all-cause mortality, microbiological eradication rates, incidence of acute kidney injury (AKI), and gastrointestinal events. The outcomes were assessed using the modified intention-to-treat (mITT) effects, per-protocol effects, and propensity score overlap weighting (PSOW) methods. Results Between July 1, 2020, and December 31, 2022, 492 hospitalized patients treated with CZA or PMB were screened at Nanjing Drum Tower Hospital. Following inclusion and exclusion criteria, 176 patients were included in the mITT analysis, and 153 in the per-protocol analysis. The clinical cure rate was significantly higher in the CZA group compared to the PMB group across all analyses. The 28-day mortality was similar between groups, while the microbial eradication rate was significantly higher in the CZA group compared to the PMB group across all analyses. The incidence of ADRs was consistent between groups, but AKI occurred more frequently in PMB patients, while gastrointestinal events were more common in the CZA group. The CZA strategy demonstrated a 28.1% increase in efficacy, with an incremental cost-effectiveness ratio of 71,651.76 yuan. Sensitivity analyses confirmed the robustness of these findings. Conclusions This study demonstrates that CZA has a higher clinical cure rate compared to PMB within a standard TTE framework. However, the overall incidence of ADRs was similar between the two treatments. Pharmacoeconomic analysis also indicated that CZA is cost-effective. Trial registration https://www.chictr.org.cn ; identifier, ChiCTR2300067946.https://doi.org/10.1007/s40121-025-01164-9Target trial emulationCeftazidime-avibactamPolymyxin BCarbapenem-resistant EnterobacteriaceaeCost-effectiveness
spellingShingle Na Hu
Fengjiao Xiao
Yechao Chen
Qiaoling Gu
Pei Liang
Yin Xu
Jinchun Liu
Yunxing Liu
Yi-chen Li
Yinqiu Xu
Mengyin Liu
Dayu Chen
Haixia Zhang
Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial Emulation
Infectious Diseases and Therapy
Target trial emulation
Ceftazidime-avibactam
Polymyxin B
Carbapenem-resistant Enterobacteriaceae
Cost-effectiveness
title Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial Emulation
title_full Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial Emulation
title_fullStr Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial Emulation
title_full_unstemmed Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial Emulation
title_short Efficacy, Safety, and Cost-Effectiveness Analysis of Ceftazidime-Avibactam versus Polymyxin B in the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections: A Target Trial Emulation
title_sort efficacy safety and cost effectiveness analysis of ceftazidime avibactam versus polymyxin b in the treatment of carbapenem resistant enterobacteriaceae infections a target trial emulation
topic Target trial emulation
Ceftazidime-avibactam
Polymyxin B
Carbapenem-resistant Enterobacteriaceae
Cost-effectiveness
url https://doi.org/10.1007/s40121-025-01164-9
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