Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting

J Antimicrob Chemother. 2015 Apr;70(4):1219-25. doi: 10.1093/jac/dku479. Epub 2014 Dec 3.

Abstract

Objectives: To evaluate the safety and clinical outcomes of patients who received carbapenem de-escalation as guided by an antimicrobial stewardship programme (ASP) in a setting where ESBL-producing Enterobacteriaceae are endemic.

Methods: Patients receiving meropenem or imipenem underwent a prospective ASP review for eligibility for de-escalation according to defined institutional guidelines. Patients in whom carbapenem was de-escalated or not de-escalated, representing the acceptance and rejection of the ASP recommendation, respectively, were compared. The primary outcome was the clinical success rate; secondary outcomes included the 30 day readmission and mortality rates, the duration of carbapenem therapy, the incidence of adverse drug reactions due to antimicrobials, the acquisition of carbapenem-resistant Gram-negative bacteria and the occurrence of Clostridium difficile-associated diarrhoea (CDAD).

Results: The de-escalation recommendations for 300 patients were evaluated; 204 (68.0%) were accepted. The patient demographics and disease severity were similar. The clinical success rates were similar [de-escalated versus not de-escalated, 183/204 (89.7%) versus 85/96 (88.5%), P=0.84], as was the survival at hospital discharge [173/204 (84.8%) versus 79/96 (82.3%), P=0.58]. In the de-escalated group, the duration of carbapenem therapy was shorter (6 versus 8 days, P<0.001), the rate of adverse drug reactions was lower [11/204 (5.4%) versus 12/96 (12.5%), P=0.037], there was less diarrhoea [9/204 (4.4%) versus 12/96 (12.5%), P=0.015], there was a lower incidence of carbapenem-resistant Acinetobacter baumannii acquisition [4/204 (2.0%) versus 7/96 (7.3%), P=0.042] and there was a lower incidence of CDAD [2/204 (1.0%) versus 4/96 (4.2%), P=0.081].

Conclusions: This study suggests that the ASP-guided de-escalation of carbapenems led to comparable clinical success, fewer adverse effects and a lower incidence of the development of resistance. This approach is safe and practicable, and should be a key component of an ASP.

Keywords: ASP; imipenem; meropenem.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use*
  • Clostridioides difficile / isolation & purification
  • Clostridium Infections / chemically induced
  • Clostridium Infections / epidemiology
  • Clostridium Infections / microbiology
  • Diarrhea / chemically induced
  • Diarrhea / epidemiology
  • Diarrhea / microbiology
  • Drug Therapy / methods
  • Drug Utilization / standards*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Endemic Diseases
  • Female
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Patient Readmission / statistics & numerical data
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • beta-Lactam Resistance*

Substances

  • Anti-Bacterial Agents
  • Carbapenems