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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 deescalation 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. [ABSTRACT FROM AUTHOR]