Antimicrobial stewardship: 
A proactive approach to combating resistance

■ Antimicrobial resistance is on the rise, but development of new and novel antimicrobial drugs is lagging.

■ Antimicrobial stewardship programs (ASPs) can help control resistance and conserve current antimicrobial drugs by maximizing appropriate use and minimizing inappropriate use.

■ ASPs can help control hospital costs, decrease length of stay, and reduce the frequency of adverse drug events.

Since their introduction in the 1940s, antimicrobial agents have significantly reduced the morbidity and mortality associated with microbial infections. Antimicrobial agents are administered for a number of indications, including chemoprophylaxis, empiric therapy, preemptive therapy, specific or targeted therapy, and maintenance or suppressive therapy. Studies suggest that 30% to 50% of all hospitalized patients will receive antibiotics,¹ and antibiotic usage is also widespread in patients who are not hospitalized. However, up to 50% of antibiotic usage is considered to be inappropriate.² Pressure created by heavy antibiotic usage (whether appropriate or inappropriate) results in the emergence/selection of resistant microorganisms.² Rising antimicrobial resistance is a major public health threat; hence, to bring international attention to this global problem, the World Health Organization made combating antimicrobial resistance the theme of World Health Day 2011.³ Not only does antibiotic misuse increase the risk for development of infections with drug-resistant organisms, it also increases the mortality associated with these infections, the length of hospital stay, and health care costs.²


The second half of the 20th century was a remarkable era that saw the introduction of many novel agents to combat microbial infections. The emergence of resistant organisms was often offset by the development of new classes of antimicrobials, so resistance concerns were downplayed.² In contrast, the 21st century has seen a dramatic decline in the development of novel antimicrobial agents.⁴ Only two drugs with novel mechanisms of action (daptomycin [Cubicin] and linezolid [Zyvox]) have been introduced since 2000.⁵ Antimicrobial resistance during this period has mushroomed worldwide both among gram-positive and gram-negative bacteria as well as among fungi.⁴ As a result, the Infectious Diseases Society of America (IDSA) has put forth a global challenge, called the 10  '20 Initiative, with the goal of developing 10 novel antimicrobial agents by the year 2020.⁶ Until novel agents are developed, evaluated, and approved for clinical use (a relatively drawn-out process), preservation of the existing therapeutic armamentarium, primarily by encouraging (or perhaps enforcing) appropriate antimicrobial usage—that is, antimicrobial stewardship—has achieved paramount importance. Additionally, the IDSA has been proactive in issuing guidelines for the development of antimicrobial stewardship programs (ASPs). ASPs along with strict adherence to infection-control practices are the main strategies for reducing the emergence and spread of resistant microorganisms.⁷ 


›THE ANTIMICROBIAL 
STEWARDSHIP TEAM 


The optimal antimicrobial stewardship team consists of core members from multiple disciplines within an institution. Typically, the team is headed by an antimicrobial steward who is either an infectious diseases physician or a clinical pharmacist with infectious disease training. Other core members include a clinical microbiologist, an infection-control practitioner, a hospital epidemiologist, and an information technology specialist. Collaboration among the members of the multidisciplinary antimicrobial stewardship team, the hospital infection-control program, the microbiology laboratory, the pharmacy, as well as the pharmacy and therapeutics and medical practice committees is critical for the success of the ASP. Support from the hospital administration is of paramount importance, particularly in establishing the necessary institutional infrastructure, delegating authority, providing compensation, ensuring compliance, and tracking outcomes. Success also depends on acceptance of and adherence to the ASP recommendations by health care providers, including primary teams, subspecialists, physician assistants, and nurse practitioners.⁷


STEWARDSHIP STRATEGIES 


Antimicrobial stewardship strategies fall into two broad categories: (1) front-end or pre-prescriptive strategies and (2) back-end or post-prescriptive strategies⁵ (Table 1). Elements of each strategy can be combined.⁷


Additional elements, based on resources and local practice behaviors, should 
be considered for integration into the ASP.⁷ Provision of guidelines for antimicrobial usage that reflect hospital-specific resistance patterns, local microbiology, and clinical outcomes can improve clinician education. The use of antimicrobial order forms can assist in implementing orders that ensure appropriate antibiotic selection. Order forms can prompt clinicians to consider factors based on clinical data, adjustments for organ dysfunctions, drug allergies, laboratory tests and pharmacokinetic monitoring, and initiating consultations, thereby increasing compliance with the ASP guidelines. Use of a combination of antimicrobial drugs, rather than monotherapy, to treat multiple drug-resistant infections in selective clinical scenarios can improve the appropriateness of antibiotic therapy and prevent the emergence of resistance. De-escalation of empiric antimicrobial therapy from broad coverage to selective coverage based on culture results can decrease selective pressure on microorganisms and reduce costs. Ensuring optimal dosage adjusted to renal function, hepatic function, patient characteristics, site of infection, and infectious organism can improve the efficacy of the ASP. Conversion of parenteral to oral antibiotics can shorten hospital stays and reduce costs. Computer-assisted surveillance can monitor antimicrobial resistance patterns, identify outbreak of nosocomial infections, and track adverse drug events.⁷