Efficacy and safety of ceftazidime-avibactam compared to other antimicrobials for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae strains, a systematic review and meta-analysis

Microb Pathog. 2023 Jun:179:106090. doi: 10.1016/j.micpath.2023.106090. Epub 2023 Mar 31.

Abstract

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a significant public health issue. CRKP infections can increase the mortality of severely ill hospitalised patients and elevate the financial burden of their hospitalisation globally. Colistin and tigecycline are the main antimicrobials which have been widely used for the treatment of CRKP infections. However, novel antimicrobials have been recently launched. Ceftazidime-avibactam (CAZ-AVI) seems one of the most efficient ones.

Aim: The aim of the current systematic literature review and meta-analysis is to assess the efficacy and safety of CAZ-AVI compared to other antimicrobials in adult patients (aged >18) with CRKP infection.

Methods: All data were retrieved using PubMed/Medline, the Web of Science and Cochrane library. The main outcome was the effective treatment of CRKP infection or the microbiological eradication of CRKP in the culture of biological samples. Secondary outcomes included the impact on 28- or 30-day mortality and adverse effects, if available. Pooled analysis was conducted using Review Manager v. 5.4.1 software (RevMan). The level of statistical significance was set at p < 0.05.

Results: CAZ-AVI was proved more effective than other antimicrobials against CRKP infections and CRKP bloodstream infections (p < 0.00001 and p < 0.0001, respectively). Patients in the CAZ-AVI arm displayed statistically lower 28- and 30-day mortality rates (p = 0.002 and p < 0.00001, respectively). Concerning the microbiological eradication, no meta-analysis was feasible due to high heterogeneity.

Conclusion: The promotion of CAZ-AVI for treating CRKP infections over other antimicrobials seems favourable. However, there is a long way ahead to reveal additional scientific findings to further strengthen this statement.

Keywords: Antimicrobial resistance; Carbapenem-resistant Klebsiella pneumoniae; Ceftazidime-avibactam; Nosocomial infections.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents*
  • Carbapenem-Resistant Enterobacteriaceae*
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Ceftazidime / pharmacology
  • Ceftazidime / therapeutic use
  • Drug Combinations
  • Humans
  • Klebsiella Infections* / drug therapy
  • Klebsiella Infections* / microbiology
  • Klebsiella pneumoniae
  • Microbial Sensitivity Tests
  • beta-Lactamases

Substances

  • avibactam, ceftazidime drug combination
  • Anti-Bacterial Agents
  • Ceftazidime
  • Drug Combinations
  • Anti-Infective Agents
  • Carbapenems
  • beta-Lactamases