Efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs): A meta-analysis of randomized controlled trials

Zhang, Yue; Tao, Lina; Qu, Xiaoyu; Niu, Junqi; Ding, Yanhua; Zhang, Sixi

doi:10.1590/1806-9282.64.03.253

Cited by 11 publications

(4 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the subgroup of patients with UTI, higher microbiological cure rates were demonstrated with CAZ-AVI at TOC. Similar results of higher microbiological cure with CAZ-AVI were also reported in a meta-analysis by Zhang et al, compiling trials of patients with cUTI and cIAI (81). Though no significant difference was demonstrated for the outcome of any adverse events (AEs), the rate of serious AEs (SAEs) was significantly higher with CAZ-AVI versus comparator, mostly carbapenem.…”

Section: Clinical Datasupporting

confidence: 80%

New β-Lactam–β-Lactamase Inhibitor Combinations

et al. 2020

View full text Add to dashboard Cite

SUMMARY The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel β-lactam–β-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitro activities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa. Ceftazidime-avibactam is a potential drug for treating Enterobacterales producing extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), AmpC, and some class D β-lactamases (OXA-48) in addition to carbapenem-resistant Pseudomonas aeruginosa. Ceftolozane-tazobactam is a treatment option mainly for carbapenem-resistant P. aeruginosa (non-carbapenemase producing), with some activity against ESBL-producing Enterobacterales. Meropenem-vaborbactam has emerged as treatment option for Enterobacterales producing ESBL, KPC, or AmpC, with similar activity as meropenem against P. aeruginosa. Imipenem-relebactam has documented activity against Enterobacterales producing ESBL, KPC, and AmpC, with the combination having some additional activity against P. aeruginosa relative to imipenem. None of these drugs present in vitro activity against Enterobacterales or P. aeruginosa producing metallo-β-lactamase (MBL) or against carbapenemase-producing Acinetobacter baumannii. Clinical data regarding the use of these drugs to treat MDR bacteria are limited and rely mostly on nonrandomized studies. An overview on eight BLBLIs in development is also provided. These drugs provide various levels of in vitro coverage of carbapenem-resistant Enterobacterales, with several drugs presenting in vitro activity against MBLs (cefepime-zidebactam, aztreonam-avibactam, meropenem-nacubactam, and cefepime-taniborbactam). Among these drugs, some also present in vitro activity against carbapenem-resistant P. aeruginosa (cefepime-zidebactam and cefepime-taniborbactam) and A. baumannii (cefepime-zidebactam and sulbactam-durlobactam).

show abstract

Section: Clinical Datasupporting

confidence: 80%

New β-Lactam–β-Lactamase Inhibitor Combinations

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In addition, results of individual RCTs have been pooled into secondary research studies, including meta-analyses and post-hoc analyses, for supporting the hypothesis that CAZ-AVI is superior to SoC for infection due to bacteria with special AMR profile. 6,[24][25][26] As it is typical when multiple meta-analyses are produced, the conclusions and the emphasis placed on the results vary among them and their results may become conflicting and even misleading. [27][28] In particular, some studies confirmed no significant difference between treatment arms, [29][30] some studies claimed better efficacy of the experimental intervention for MDR bacteria [25][26] while other studies suggested that the experimental intervention was more toxic than the comparator.…”

Section: Ceftazidime/avibactam: An Overview Of Current Knowledge Frommentioning

confidence: 99%

“…6,[24][25][26] As it is typical when multiple meta-analyses are produced, the conclusions and the emphasis placed on the results vary among them and their results may become conflicting and even misleading. [27][28] In particular, some studies confirmed no significant difference between treatment arms, [29][30] some studies claimed better efficacy of the experimental intervention for MDR bacteria [25][26] while other studies suggested that the experimental intervention was more toxic than the comparator. 24 Non-inferiority randomized controlled trials for antibiotics: ethical and clinical practice implications NI-RCTs are typically presented as a pragmatic design that can compare a new intervention against an established SoC.…”

Section: Ceftazidime/avibactam: An Overview Of Current Knowledge Frommentioning

confidence: 99%

“…55 One-sided significance has been chosen as the experimental arm will include an approved drug, which proved to be non-inferior to SoC, and has (yet unproven) potential for superiority in selected sub-set of patients such as those with CR-GBNs infections. 6,[24][25][26] To optimize statistical power, all analyses are carried out on all participants for whom eligibility criteria can be ascertained after randomization (i.e. a CR-GNB has been isolated from a blood sample taken before treatment allocation).…”

Section: Ceftazidime/avibactam: An Overview Of Current Knowledge Frommentioning

confidence: 99%

See 1 more Smart Citation

Non-inferiority versus superiority trial design for new antibiotics in an era of high antimicrobial resistance: the case for post-marketing, adaptive randomised controlled trials

Lanini

Ioannidis

Vairo

et al. 2019

The Lancet Infectious Diseases

View full text Add to dashboard Cite

Antimicrobial resistance (AMR) is one of the most important threats to global health security. A range of Gram-negative bacteria (GNB) associated with high morbidity and mortality rates are now resistant to virtually all available antibiotics. In this context of urgency to develop novel drugs, new antibiotics for multi drug resistant (MDR) GNB (namely, ceftazidime-avibactam, plazomicin and meropenem-varbobactam) have been approved by regulatory authorities on grounds of non-inferiority trials which provided no direct evidence of their efficacy against MDR such as Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cepacia and Acinetobacter baumannii. The use of noninferiority and superiority trials and selection of appropriate and optimal study designs remains a major challenge in the development, registration, and post-marketing implementation of new antibiotics. Using as an example, the development process of ceftazidime-avibactam, we propose a strategy for a new research framework based on adaptive randomized clinical trials (aRCTs). The operational research strategy has the aim of assessing the efficacy of new antibiotics in special groups of patients, such as those infected with MDR bacteria, who were not included in earlier phase studies, and for whom it is important to establish an appropriate standard of care. 82. Highlights of prescribing information Vabomere™ (meropenem and vaborbactam) Food and Drug

show abstract

Evaluation of the efficacy and safety of ceftazidime/avibactam in the treatment of Gram-negative bacterial infections: a systematic review and meta-analysis

Zhong

Zhao

Zhang

et al. 2018

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

Efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs): A meta-analysis of randomized controlled trials

Abstract: Efficacy and safEty of cEftazidimE-avibactam in thE trEatmEnt of complicatEd intra-abdominal infEctions (ciais)

Cited by 11 publications

References 26 publications

New β-Lactam–β-Lactamase Inhibitor Combinations

New β-Lactam–β-Lactamase Inhibitor Combinations

Non-inferiority versus superiority trial design for new antibiotics in an era of high antimicrobial resistance: the case for post-marketing, adaptive randomised controlled trials

Evaluation of the efficacy and safety of ceftazidime/avibactam in the treatment of Gram-negative bacterial infections: a systematic review and meta-analysis

Contact Info

Product

Resources

About