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Update of clinical application in ceftazidime–avibactam for multidrug-resistant Gram-negative bacteria infections

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Abstract

Purpose

Multidrug-resistant Gram-negative bacteria (MDR-GNB) have become a major global public health threat. Ceftazidime–avibactam (CAZ–AVI) is a newer combination of β-lactam/β-lactamase inhibitor, with activity against carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). The aim of this review is to describe the recent real-world experience of CAZ–AVI for the infections due to MDR-GNB.

Methods

We searched PubMed, Embase and Google Scholar for clinical application in CAZ-AVI for MDR-GNB infections. Reference lists were reviewed and synthesized for narrative review.

Results

MDRGNB infections are associated with higher mortality significantly comparing to drug-susceptible bacterial infections. Fortunately, CAZ–AVI shows significant benefits for infections due to KPC or OXA-48 CRE, comparing to colistin, carbapenem, aminoglycoside and other older agents, even in those with immunocompromised status. The efficacy of CAZ–AVI varies in different infection sites due to CRE, which is lower in pneumonia. Early use is associated with improved clinical outcomes. Noteworthy, when adopted as salvage therapy, CAZ–AVI is still superior to other GNB active antibiotics. CAZ–AVI plus aztreonam is recommended as the first line of MBL-CRE infections. However, for infections caused by KPC- and OXA-48-producing isolates, further investigations are needed to demonstrate the benefit of combination therapy. Besides CRE, CAZ-AVI is also active to MDR-PA. However, the development of resistance in CRE and MDR-PA against CAZ–AVI is alarming, and more investigations and studies are needed to prevent, diagnose, and treat infections due to CAZ–AVI-resistant pathogens.

Conclusions

CAZ-AVI appears to be a valuable therapeutic option in MDR-GNB infections. Using CAZ-AVI appropriately to improve efficacy and decrease the emergence of resistance is important.

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This work received grant from funding CAMS Innovation Fund for Medical Sciences (CIFMS) 2021-I2M-C&T-B-080 and 2021-I2M-017.

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  1. Sisi Zhen and Hui Wang are co-authors.

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  1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, 300020, China

    Sisi Zhen, Hui Wang & Sizhou Feng

  2. Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong Province, China

    Hui Wang

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Zhen, S., Wang, H. & Feng, S. Update of clinical application in ceftazidime–avibactam for multidrug-resistant Gram-negative bacteria infections. Infection 50, 1409–1423 (2022). https://doi.org/10.1007/s15010-022-01876-x

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