Longitudinal Multicenter Susceptibility Trends of Ceftazidime/Avibactam and Imipenem/Relebactam and Dose Optimization in Critically Ill Patients with Carbapenem-Resistant Enterobacterales Bloodstream Infections

@article{wang2026longitudinal,
  title = {{Longitudinal Multicenter Susceptibility Trends of Ceftazidime/Avibactam and Imipenem/Relebactam and Dose Optimization in Critically Ill Patients with Carbapenem-Resistant Enterobacterales Bloodstream Infections}},
  author = {Wang X and Chen P and Chen T and Xiong L and Yi Z and Chen Y and Shen P and Ji J and Ying C and Liu Z and Xiao Y},
  journal = {Drug Design, Development and Therapy},
  year = {2026},
  month = nov,
  url = {https://www.dovepress.com/longitudinal-multicenter-susceptibility-trends-of-ceftazidimeavibactam-peer-reviewed-fulltext-article-DDDT},
  note = {CC BY},
}

TY  - JOUR
TI  - Longitudinal Multicenter Susceptibility Trends of Ceftazidime/Avibactam and Imipenem/Relebactam and Dose Optimization in Critically Ill Patients with Carbapenem-Resistant Enterobacterales Bloodstream Infections
AU  - Wang X
AU  - Chen P
AU  - Chen T
AU  - Xiong L
AU  - Yi Z
AU  - Chen Y
AU  - Shen P
AU  - Ji J
AU  - Ying C
AU  - Liu Z
AU  - Xiao Y
PY  - 2026
DA  - 2026/11/08
JO  - Drug Design, Development and Therapy
UR  - https://www.dovepress.com/longitudinal-multicenter-susceptibility-trends-of-ceftazidimeavibactam-peer-reviewed-fulltext-article-DDDT
AB  - Xueting Wang,1,* Pan Chen,2,3,* Tao Chen,1,4 Luying Xiong,1,5 Zijian Yi,1 Yunbo Chen,1 Ping Shen,1 Jinru Ji,1 Chaoqun Ying,1 Zhiying Liu,1 Yonghong Xiao1– 3 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Peking Union Medical College & Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Structure and Morphology, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China; 4Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, People’s Republic of China; 5Department of Respiratory Medicine, Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong Xiao, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China, Tel +865 718 723 6421, Email [email protected]: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections cause high mortality in critically ill patients, where altered pharmacokinetics undermine treatment. Comparative data on ceftazidime/avibactam (CZA) and imipenem/relebactam (IMR) remain scarce, especially in patients with augmented renal clearance (ARC) or receiving continuous renal replacement therapy (CRRT).Methods: We analyzed 27,771 bloodstream infection (BSI) Enterobacterales isolates (1543 CRE) from 61 Chinese hospitals (2022– 2024) for species distribution and susceptibility to CZA, IMR and other antibiotics. Monte Carlo simulation (MCS) assessed the joint probability of target attainment (PTA) and joint cumulative fraction of response (CFR) of IMR in ARC or CRRT patients.Results: Among BSI CRE, carbapenem-resistant Klebsiella pneumoniae (CRKP) predominated (75.4%), followed by carbapenem-resistant Escherichia coli (CREC) (11.7%) and carbapenem-resistant Enterobacter cloacae (CRECL) (6.7%). Against CRKP, IMR exhibited superior activity to CZA (MIC90 2/4 vs > 32/4 mg/L). Against CREC and CRECL, both agents showed limited activity, though IMR maintained lower MIC90 (8/4 vs > 32/4 mg/L). CZA resistance among CRE rose from 17.1% in 2021 to 33.6% in 2023, then fell to 18.8% in 2024; IMR resistance remained lower, declining from 15.5% in 2022 to 13.1% in 2024. In ARC patients, IMR achieved joint PTA > 90% but suboptimal CFR against CRKP (83.6%/81.4%) and failed against other CRE. In patients with continuous veno-venous hemofiltration (CVVH), 1.25 g, 1 g, and 0.75 g q6h achieved optimal CFR (> 90%) against CRKP; only the two highest doses reached suboptimal levels (> 80%) against other CRE. In patients with continuous veno-venous hemodiafiltration (CVVHDF), 1.25 g and 1 g q6h achieved optimal CFR against CRKP; against non-CRKP, only 1.25 g q6h reached suboptimal coverage.Conclusion: IMR is a valuable option for CRKP infections, especially in patients on CRRT. But its coverage varies by species, and it falls short in ARC patients and against non-CRKP pathogens. Dosing should be guided by species identification, susceptibility results, renal function, CRRT modality, and local resistance surveillance.Keywords: carbapenem-resistant enterobacterales, imipenem/relebactam, ceftazidime/avibactam, Monte Carlo simulation, critically ill patients
SN  - 1177-8881
ER  -