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The objective of the study was to assess health care providers' (HCPs) knowledge and attitude toward antimicrobial resistance (AMR) and implement an antimicrobial stewardship program (ASP) in a long-term acute care hospital (LTACH).A questionnaire on antibiotic use and resistance was administered to HCP in an LTACH in Detroit, Michigan, between August 2011 and October 2011. Concurrently, a retrospective review of common antibiotic prescription practices and costs was conducted. Then, a tailored ASP was launched at the LTACH followed by 2-phase postimplementation assessment aiming at evaluating the impact of the ASP on antibiotic expenditure.Of all respondents (N = 26), 65% viewed AMR as a national problem, but only 38% perceived AMR as a problem at their facility. Most respondents were familiar with infections caused by resistant organisms such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and extended-spectrum β-lactamase; however, only 35% expressed confidence in treating infected patients. In the preimplementation phase, 15% of antimicrobial doses were inappropriate and 10 of 13 de-escalation opportunities were missed, resulting in additional $23,524.00 expenditure. In the first postimplementation phase, there was a 42% and 58% decrease in the use of daptomycin and tigecycline, respectively, resulting in $55,000 savings. In the second postintervention phase, total antimicrobial cost for treating a cohort of 28 patients in 2016 and 2017 was $26,837.85 and $22,397.15, respectively.Introduction of an ASP in an LTACH improves antimicrobial prescribing practices, reduces cost, and is sustainable.