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

Zhong, Han; Zhao, Xianyuan; Zhang, Zaili; Z, Gu; Zhang, Chi; Gao, Yuan; Cui, Min

doi:10.1016/j.ijantimicag.2018.07.004

Cited by 47 publications

(34 citation statements)

References 41 publications

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“…In particular, significantly increased cure rates were achieved with CAZ-AVI in infections from resistant causative microorganisms (RR = 1.61; 95% CI, 1.13–2.29); reduced mortality was also reported (RR = 0.29; 95% CI, 0.13–0.63). Similar results were reported for cUTIs and BSI (195).…”

Section: New Antibioticssupporting

confidence: 89%

The “Old” and the “New” Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How

Karaiskos

Lagou

Pontikis

et al. 2019

Front. Public Health

226

166

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The recent expansion of multidrug resistant and pan-drug-resistant pathogens poses significant challenges in the treatment of healthcare associated infections. An important advancement, is a handful of recently launched new antibiotics targeting some of the current most problematic Gram-negative pathogens, namely carbapenem-producing Enterobacteriaceae (CRE) and carbapenem-resistant P. aeruginosa (CRPA). Less options are available against carbapenem-resistant Acinetobacter baumannii (CRAB) and strains producing metallo-beta lactamases (MBL). Ceftazidime-avibactam signaled a turning point in the treatment of KPC and partly OXA- type carbapenemases, whereas meropenem-vaborbactam was added as a potent combination against KPC-producers. Ceftolozane-tazobactam could be seen as an ideal beta-lactam backbone for the treatment of CRPA. Plazomicin, an aminoglycoside with better pharmacokinetics and less toxicity compared to other class members, will cover important proportions of multi-drug resistant pathogens. Eravacycline holds promise in the treatment of infections by CRAB, with a broad spectrum of activity similar to tigecycline, and improved pharmacokinetics. Novel drugs and combinations are not to be considered “panacea” for the ongoing crisis in the therapy of XDR Gram-negative bacteria and colistin will continue to be considered as a fundamental companion drug for the treatment of carbapenem-resistant Enterobacteriaceae (particularly in areas where MBL predominate), for the treatment of CRPA (in many cases being the only in vitro active drug) as well as CRAB. Aminoglycosides are still important companion antibiotics. Finally, fosfomycin as part of combination treatment for CRE infections and P. aeruginosa , deserves a greater attention. Optimal conditions for monotherapy and the “when and how” of combination treatments integrating the novel agents will be discussed.

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Section: New Antibioticssupporting

confidence: 89%

The “Old” and the “New” Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How

Karaiskos

Lagou

Pontikis

et al. 2019

Front. Public Health

226

166

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“…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%

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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

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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

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“…The risk of bias of retrospective studies will be evaluated according to the Newcastle-Ottawa Scale (NOS) (26). The items with regard to patient selection, comparability between groups, and outcome or exposure factor assessment will be estimated (27). The risk of bias of individual studies will be rated as low (NOS scores ≥7), moderate (4≤ NOS scores ≤6), or high (NOS scores ≤3).…”

Section: Quality Assessmentmentioning

confidence: 99%

Current therapeutic options for coronavirus disease 2019 (COVID-19)—lessons learned from severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) therapy: a systematic review protocol

Zhang¹,

Zhong²,

Liu³

et al. 2020

Ann Transl Med

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Background: Coronavirus disease 2019 , also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, first manifested in December 2019, and spread rapidly worldwide.Facing this lethal disease, there is an urgent need to develop potent therapies against SARS-CoV-2 infection. SARS-CoV-2 phylogenetically and symptomatically resembles SARS-CoV and Middle East RespiratorySyndrome Coronavirus (MERS-CoV). Numerous agents have been utilised during the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) epidemics, which may show some benefit against SARS-CoV-2.Methods: MEDLINE, EMBASE, Cochrane Library, CBM Disc, China National Knowledge Infrastructure, Wanfang Data, and the China Science and Technology Journal Database will be searched.Manual searches will be conducted by searching pre-printing websites, clinical trial registers, and screening the reference lists of inclusive studies. The screening of all citations and the selection of inclusive articles will be conducted by two reviewers. Randomised controlled trials (RCTs) and controlled cohort studies reporting antiviral therapies, including ribavirin, remdesivir, lopinavir/ritonavir, arbidol, chloroquine, hydroxychloroquine, and interferon, for SARS, MERS, and COVID-19 will be included. The primary outcomes will be mortality, incidence of acute respiratory distress syndrome, and utilisation of mechanical ventilation and intensive care unit admission. The secondary outcomes will be improvement in symptoms and chest radiography results, virus clearance, changes in blood test results, and serum tests. The quality of the retrieved RCTs and observational studies will be appraised according to the Cochrane risk of bias tool and the Newcastle-Ottawa Scale, respectively. If feasible, we will perform a fixed-or random-effects metaanalysis.Discussion: This systematic review and meta-analysis will summarise all the available evidence for the efficacy and safety of current therapeutic options in SARS-CoV, MERS-CoV, or SARS-CoV-2-infected patients. The findings of this study may inform subsequent antiviral interventions for patients with COVID-19.

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

Cited by 47 publications

References 41 publications

The “Old” and the “New” Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How

The “Old” and the “New” Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How

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

Current therapeutic options for coronavirus disease 2019 (COVID-19)—lessons learned from severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) therapy: a systematic review protocol

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