Ceftazidime-Avibactam in the Treatment of Patients with Bacteremia or Nosocomial Pneumonia: A Systematic Review and Meta-analysis

Ryan K Shields; Juan P Horcajada; Shweta Kamat; Paurus M Irani; Margaret Tawadrous; Tobias Welte

doi:10.1007/s40121-024-00999-y

Ceftazidime-Avibactam in the Treatment of Patients with Bacteremia or Nosocomial Pneumonia: A Systematic Review and Meta-analysis

Infect Dis Ther. 2024 Jul;13(7):1639-1664. doi: 10.1007/s40121-024-00999-y. Epub 2024 May 31.

Authors

Ryan K Shields¹, Juan P Horcajada^{2

3}, Shweta Kamat⁴, Paurus M Irani⁵, Margaret Tawadrous⁶, Tobias Welte⁷

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
² Department of Infectious Diseases, Hospital Del Mar, Institut Hospital Del Mar d'Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
³ Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III CIBERINFEC, Madrid, Spain.
⁴ Pfizer Ltd., Mumbai, India. shweta.kamat@pfizer.com.
⁵ Pfizer Ltd., Surrey, UK.
⁶ Pfizer Inc., New York, USA.
⁷ Department of Respiratory Medicine and Infectious Disease, Member of the German Center of Lung Research, Hannover School of Medicine, Hannover, Germany.

Abstract

Introduction: Ceftazidime-avibactam (CAZ-AVI) is a combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam that is approved for the treatment of pediatric (≥ 3 months) and adult patients with complicated infections including hospital-acquired and ventilator-associated pneumonia (HAP/VAP), and bacteremia. This systematic literature review and meta-analysis (PROSPERO registration: CRD42022362856) aimed to provide a quantitative and qualitative synthesis to evaluate the effectiveness of CAZ-AVI in treating adult patients with bacteremia or nosocomial pneumonia caused by carbapenem-resistant Enterobacterales (non metallo-β-lactamase-producing strains) and multi-drug resistant (MDR) Pseudomonas aeruginosa infections.

Methods: The databases included in the search, until November 7, 2022, were Embase and PubMed. A total of 24 studies (retrospective: 22, prospective: 2) with separate outcomes for patients with bacteremia or pneumonia were included.

Results: The outcomes assessed were all-cause mortality, clinical cure, and microbiological cure. Qualitative (24 studies) and quantitative (8/24 studies) syntheses were performed. The quality of the studies was assessed using the MINORS checklist and the overall risk of bias was moderate to high.

Conclusions: In studies included in the meta-analysis, lower all-cause mortality for patients with bacteremia (OR = 0.30, 95% CI 0.19-0.46) and improved rates of clinical cure for patients with bacteremia (OR = 4.90, 95% CI 2.60-9.23) and nosocomial pneumonia (OR = 3.20, 95% CI 1.55-6.60) was observed in the CAZ-AVI group compared with the comparator group. Data provided here may be considered while using CAZ-AVI for the treatment of patients with difficult-to-treat infections.

Systematic review registration: PROSPERO CRD42022362856.

Keywords: Bacteremia; Ceftazidime-avibactam; Clinical cure; Hospital-associated pneumonia; Mortality; Nosocomial pneumonia; Ventilator-associated pneumonia.