Antimicrobial Stewardship Programs: Effects on Clinical and Economic Outcomes and Future Directions

Historical Background

Modern antibiotics date back to the late 1930s when penicillin and sulfonamides were introduced to the medical market, and resistance to these drug classes was reported just a few years after their introduction. The same bacterial resistance mechanisms that neutralized their efficacy then exist today, and these mechanisms continue to confer resistance among those classes [5].

While “stewardship” was not described as such until the late 1990s [12], institutions have historically been proactive in creating standards around antimicrobial utilization to encourage judicious use of these agents. The earliest form of tracking antibiotic use was in the form of paper charts as “antibiotic logs” [9] and “punch cards” [10] in the 1960s. The idea of a team approach to stewardship dates back to the 1970s, with the example of Hartford Hospital in Hartford, Connecticut, which employed an antimicrobial standards model run by an infectious disease (ID) physician and clinical pharmacists [11]. In 1977, the Infectious Diseases Society of America (IDSA) released a statement that clinical pharmacists may have a substantial impact on patient care, including in ID, contributing to the idea that a team of physicians collaborating with pharmacists presents the best way to combat inappropriate medication use. Pharmacist involvement has since been shown to restrict broad overutilized antimicrobial agents and reduce the rate of C. difficile infection by a significant amount [13].

In 1997 the IDSA and the Society for Healthcare Epidemiology of America (SHEA) published guidelines to assist in the prevention of the growing issue of resistance, mentioning the importance of antimicrobial stewardship [14]. A decade later they released joint guidelines for ASP implementation [15], and the Pediatric Infectious Disease Society (PIDS) joined them in 2012 to publish a joint statement acknowledging and endorsing stewardship [16]. In 2014, the Centers of Disease Control and Prevention (CDC) recommended that every hospital should have an ASP. As of 1 January 2017, the Joint Commission requires an ASP as a standard for accreditation at hospitals, critical access hospitals, and nursing care [17]. Guidelines for implementation of an ASP are currently available through the IDSA and SHEA [1,16].

ASP Interventions

There are 2 main strategies that ASPs have to combat inappropriate antimicrobial use, and each has its own set of systematic interventions. These strategies are referred to as “prospective audit with intervention and feedback” and “prior authorization” [6]. Although most ASPs will incorporate these main strategies, each institution typically creates its own strategies and regulations independently.

Prospective audit with intervention and feedback describes the process of providing recommendations after reviewing utilization and trends of antimicrobial use. This is sometimes referred to as the “back-end” intervention, in which decisions are made after antibiotics have been administered. Interventions that are commonly used under this strategy include discontinuation of antibiotics due to culture data, de-escalation to drugs with narrower spectra, IV to oral conversions, and cessation of surgical prophylaxis [6].

Prior authorization, also referred to as a “front-end” intervention, is the process of approving medications before they are used. Interventions include a restricted formulary for antimicrobials that can be managed through a paging system or a built-in computer restriction program, as well as other guidelines and protocols for dosing and duration of therapy. Restrictions typically focus on broad spectrum antibiotics as well as the more costly drugs on formularies. These solutions reduce the need for manual intervention as technology makes it possible to create automated restriction-based services that prevent inappropriate prescribing [6].

Aside from these main techniques, other strategies are taken to achieve the goal of attaining optimal clinical outcomes while limiting further antimicrobial resistance and adverse effects. Different clinical settings have different needs, and ASPs are customized to each setting’s resources, prescribing habits, and other local specificities [1]. These differences present difficulty with interpreting diverse datasets, but certain themes arise in the literature: commonly assessed clinical outcomes of inpatient ASPs include hospital length of stay (LOS) and readmission, reinfection, mortality, and resistance rates. These outcomes are putatively driven by the more prudent use of antimicrobials, particularly by decreased rates of antimicrobial consumption.

ASP Team Members

While ASPs may differ between institutions, the staff members involved are typically the same, and leadership is always an important aspect of a program. The CDC recommends that ASP leadership consist of a program leader (an ID physician) and a pharmacy leader, who co-lead the team [18]. In addition, the Joint Commission recommends that the multidisciplinary team should include an infection preventionist (ie, infection control and hospital epidemiologist) and practitioner [17]; these specialists have a role in prevention, awareness, and policy [19]. The integration of infection control with stewardship yields the best results [15], as infection control aims to prevent antibiotic use altogether, while stewardship increases the quality of antibiotic regimens that are being prescribed [20].

It is also beneficial to incorporate a microbiologist as an integral part of the team, responsible for performing and interpreting laboratory data (ie, cultures). Nurses should be integrated into ASPs due to the overlap of their routine activities with ASP interventions [21]; other clinicians (regardless of their infectious disease clinical background), quality control, information technology, and environmental services should all collaborate in the hospital-wide systems related to the program where appropriate [18].

Evidence Review