Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02313-19. doi: 10.1128/AAC.02313-19. Print 2020 Apr 21.

Abstract

The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections remains unknown. This was a multicenter, retrospective cohort study of adults with CRE infections who received ceftazidime-avibactam or meropenem-vaborbactam for ≥72 hours from February 2015 to October 2018. Patients with a localized urinary tract infection and repeat study drug exposures after the first episode were excluded. The primary endpoint was clinical success compared between treatment groups. Secondary endpoints included 30- and 90-day mortality, adverse events (AE), 90-day CRE infection recurrence, and development of resistance in patients with recurrent infection. A post hoc subgroup analysis was completed comparing patients who received ceftazidime-avibactam monotherapy, ceftazidime-avibactam combination therapy, and meropenem-vaborbactam monotherapy. A total of 131 patients were included (ceftazidime-avibactam, n = 105; meropenem-vaborbactam, n = 26), 40% of whom had bacteremia. No significant difference in clinical success was observed between groups (62% versus 69%; P = 0.49). Patients in the ceftazidime-avibactam arm received combination therapy more often than patients in the meropenem-vaborbactam arm (61% versus 15%; P < 0.01). No difference in 30- and 90-day mortality resulted, and rates of AE were similar between groups. In patients with recurrent infection, development of resistance occurred in three patients that received ceftazidime-avibactam monotherapy and in no patients in the meropenem-vaborbactam arm. Clinical success was similar between patients receiving ceftazidime-avibactam and meropenem-vaborbactam for treatment of CRE infections, despite ceftazidime-avibactam being used more often as a combination therapy. Development of resistance was more common with ceftazidime-avibactam monotherapy.

Keywords: Gram-negative resistance; carbapenem-resistant Enterobacteriaceae; ceftazidime-avibactam; meropenem-vaborbactam.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Azabicyclo Compounds / therapeutic use*
  • Boronic Acids / therapeutic use*
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • Carbapenems*
  • Ceftazidime / therapeutic use*
  • Cohort Studies
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Female
  • Humans
  • Male
  • Meropenem / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / microbiology
  • beta-Lactamase Inhibitors / pharmacology

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Boronic Acids
  • Carbapenems
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • beta-Lactamase Inhibitors
  • vaborbactam
  • avibactam
  • Ceftazidime
  • Meropenem