Treating complicated carbapenem-resistant enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation

Fiorella Krapp*, Jennifer L. Grant, Sarah H. Sutton, Egon A. Ozer, Viktorija O. Barr

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Ceftazidime/avibactam (CAZ/AVI) is the first antimicrobial agent with activity against carbapenem-resistant Enterobacteriaceae (CRE) approved by the US Food and Drug Administration (FDA). Notably, human clinical outcome data for this indication are limited. Therefore, a retrospective study was performed to evaluate the clinical outcomes and bacterial genomic characteristics of patients hospitalised at a tertiary medical centre with CRE infections treated for the first time with CAZ/AVI. From a total of 44 patients with CRE infections, 6 patients were treated with CAZ/AVI. The duration of CAZ/AVI treatment ranged from 7 days to 28 days. Five patients achieved clinical cure, however two relapsed with the same carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain within 3 weeks of completion of CAZ/AVI treatment. In addition, one patient with CR-Kp pneumonia experienced clinical failure despite having a documented CAZ/AVI-susceptible CR-Kp strain [minimum inhibitory concentration (MIC) = 2 mg/L]. Consequently, the overall rate of unsuccessful outcome in this small cohort of patients was 50%. All strains carried KPC-3, OXA-9 and different TEM and SHV β-lactamases, but none carried the intrinsically avibactam-resistant class B metallo-β-lactamases. No obvious differences in antibiotic resistance genes were observed. This study provides an early glimpse of the clinical outcomes of patients with CR-Kp infections treated with CAZ/AVI. Findings of clinical failure and relapse in patients with no prior exposure to CAZ/AVI and with documented susceptibility to CAZ/AVI highlight the urgent need for well-designed clinical studies evaluating the effectiveness of CAZ/AVI in the treatment of CRE infections.

Original languageEnglish (US)
Pages (from-to)770-773
Number of pages4
JournalInternational Journal of Antimicrobial Agents
Volume49
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

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Keywords

  • Carbapenem-resistant Enterobacteriaceae
  • Ceftazidime/avibactam
  • Klebsiella pneumoniae
  • Multidrug resistance
  • β-Lactamase inhibitor

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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