title: Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, 117543 Singapore.
authors.forename: Kaung Yuan
authors.initials: KY
authors.lastname: Lew
authors.affiliation: Department of Pharmacy, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng 308433, Singapore.
authors.forename: Tat Ming
authors.initials: TM
authors.lastname: Ng
authors.affiliation: Department of Pharmacy, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng 308433, Singapore.
authors.forename: Michelle
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng 308433, Singapore.
authors.forename: Sock Hoon
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng 308433, Singapore.
authors.forename: Ee Ling
authors.initials: EL
authors.lastname: Lew
authors.affiliation: Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Department of Infectious Disease, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng 308433, Singapore.
authors.forename: Li Min
authors.initials: LM
authors.lastname: Ling
authors.affiliation: Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Department of Infectious Disease, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng 308433, Singapore.
authors.forename: Brenda
authors.initials: B
authors.lastname: Ang
authors.affiliation: Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Department of Infectious Disease, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng 308433, Singapore Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road 119228, Singapore.
authors.forename: David
authors.initials: D
authors.lastname: Lye
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, 117543 Singapore Department of Pharmacy, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng 308433, Singapore christeng@nus.edu.sg.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Teng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000302:isolation & purification; D003015:Clostridium Infections / Q000139:chemically induced / Q000453:epidemiology / Q000382:microbiology; D003967:Diarrhea / Q000139:chemically induced / Q000453:epidemiology / Q000382:microbiology; D004358:Drug Therapy / Q000379:methods; D004363:Drug Utilization / Q000592:standards*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D019353:Endemic Diseases; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission / Q000706:statistics & numerical data; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems
keywords: ASP; imipenem; meropenem