title: Efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae: an open-label randomized controlled trial.
abstract: Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria (GNB) infections. The study objectives were to evaluate efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae.
  
  
  
  We conducted a randomized controlled trial of adult patients with documented ESBL-producing Enterobacteriaceae infections who had received any group 2 carbapenem for less than 96 h. In the intervention group, the previously-prescribed group 2 carbapenem was de-escalated to ertapenem. In the control group, the group 2 carbapenem was continued.
  
  
  
  During June 2011-December 2014, 32 patients were randomized to the de-escalation group and 34 to the control group. Most common sites of infection were urinary tract infection (42%). Characteristics of both groups were comparable. By using a 15% predefined margin, ertapenem was non-inferior to control group regarding the clinical cure rate (%Δ = 14.0 [95% confidence interval: -2.4 to 31.1]), the microbiological eradication rate (%Δ = 4.1 [-5.0 to 13.4]), and the superimposed infection rate (%Δ = -16.5 [-38.4 to 5.3]). Patients in the de-escalation group had a significantly lower 28-day mortality rate (9.4% vs. 29.4%; P = .05), a significantly shorter median length of stay (16.5 days [4.0-73.25] vs. 20.0 days [1.0-112.25]; P = .04), and a significantly lower defined daily dose of carbapenem use (12.9 ± 8.9 vs. 18.4 ± 12.6; P = .05).
  
  
  
  Ertapenem could be safely used as de-escalation therapy for ESBL-producing Enterobacteriaceae infections, once the susceptibility profiles are known. Future studies are needed to investigate ertapenem efficacy against ESBL-producing Enterobacteriaceae pneumonia to determine its applicability in life-threatening conditions.
  
  
  
  ClinicalTrials.gov identifier: NCT01297842 . Registered on 14 February 2011. First patient enrolled on 27 June 2011.
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pinyo
authors.identifier: 0000-0002-2964-6732
authors.initials: P
authors.lastname: Rattanaumpawan
authors.affiliation: Department of Preventive Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Peerawong
authors.initials: P
authors.lastname: Werarak
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Anupop
authors.initials: A
authors.lastname: Jitmuang
authors.affiliation: Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pattarachai
authors.initials: P
authors.lastname: Kiratisin
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. visanu.tha@mahidol.ac.th.
authors.forename: Visanu
authors.initials: V
authors.lastname: Thamlikitkul
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015780:Carbapenems / Q000627:therapeutic use*; D004755:Enterobacteriaceae / Q000235:genetics / Q000472:pathogenicity*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D000077727:Ertapenem; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D047090:beta-Lactams; D001618:beta-Lactamases; D000077727:Ertapenem
keywords: Carbapenem; De-escalation; ESBL; Enterobacteriaceae; Ertapenem