Ceftazidime-Avibactam Therapy Versus Ceftazidime-Avibactam-Based Combination Therapy in Patients With Carbapenem-Resistant Gram-Negative Pathogens: A Meta-Analysis.

Dan Li,Xiangning Huang,Shanshan Long,Hao Zhou,Fan Fei,Jie Zhang,Hua Yu

doi:10.3389/fphar.2021.707499

Abstract

Objective: To systematically review and compare the efficacy and posttreatment resistance of ceftazidime-avibactam therapy and ceftazidime-avibactam-based combination therapy in patients with Gram-negative pathogens.Methods: PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases were searched from their inception up to March 31, 2021, to obtain studies on ceftazidime-avibactam therapy versus ceftazidime-avibactam-based combination therapy in patients with carbapenem-resistant Gram-negative pathogens. The primary outcome was mortality rate, and the second outcomes were microbiologically negative, clinical success, and the development of resistance after ceftazidime-avibactam treatment.Results: Seventeen studies representing 1,435 patients (837 received ceftazidime-avibactam-based combination therapy and 598 received ceftazidime-avibactam therapy) were included in the meta-analysis. The results of the meta-analysis showed that no statistically significant difference was found on mortality rate (Petos odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.79–1.34), microbiologically negative (OR = 0.99, 95% CI 0.54–1.81), and clinical success (OR =0.95, 95% CI 0.64–1.39) between ceftazidime-avibactam-based combination therapy and ceftazidime-avibactam therapy. Although there was no difference in posttreatment resistance of ceftazidime-avibactam (OR = 0.65, 95% CI 0.34–1.26) in all included studies, a trend favoring the combination therapy was found (according to the pooled three studies, OR = 0.18, 95% CI 0.04–0.78).Conclusions: The current evidence suggests that ceftazidime-avibactam-based combination therapy may not have beneficial effects on mortality, microbiologically negative, and clinical success to patients with carbapenem-resistant Gram-negative pathogens. A trend of posttreatment resistance occurred more likely in ceftazidime-avibactam therapy than the combination therapy. Due to the limited number of studies that can be included, additional high-quality studies are needed to verify the above conclusions.

Highlights

Infections caused by carbapenem-resistant Gram-negative bacilli (CRGN) are challenging and associated with a high mortality rate (CDC, 2019); it spreads rapidly in the past decade causing a huge public health burden (Bassetti et al, 2017; Avendano et al, 2020; Zhen et al, 2021)
The article search and reference inspection were performed by two researchers independently screening the titles and abstracts and examining the full texts and reference lists according to the inclusion and exclusion criteria listed below and (Bassetti et al, 2017) cross-checking each other’s studies
The database search described in Database Search generated 17 eligible articles (Sousa et al, 2018; Kuang et al, 2020; Guimarães et al, 2019; Rathish et al, 2021; Shields et al, 2018; Tumbarello et al, 2019; Ackley et al, 2020; Iannaccone et al, 2020; Castón et al, 2020; Tumbarello et al, 2021; Zhu et al, 2021; King et al, 2017; Temkin et al, 2017; De la Calle et al, 2019; Chen et al, 2020; Jiang et al, 2020; Jorgensen et al, 2020)

Summary

Introduction

Infections caused by carbapenem-resistant Gram-negative bacilli (CRGN) are challenging and associated with a high mortality rate (CDC, 2019); it spreads rapidly in the past decade causing a huge public health burden (Bassetti et al, 2017; Avendano et al, 2020; Zhen et al, 2021). In 2015, CAZ-AVI was first approved for marketing by the US Food and Drug Administration (FDA) for the treatment of adults (age >18) with serious infections including complicated intra-abdominal infection (cIAI) (along with metronidazole) and complicated urinary tract infection (cUTI) (Administration USFaD., 2015). This scenario occurred only when there were limited or no other therapeutic options. A wealth of CAZ-AVI-treating CRGN studies in real-world practice has been reported. This debate occurred in the posttreatment CAZ-AVI scenario (Shields et al, 2018; Tumbarello et al, 2019; Ackley et al, 2020; Castón et al, 2020; Iannaccone et al, 2020; Tumbarello et al, 2021)

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Discussion

Conclusion