Antimicrobial stewardship

The 2007 definition by the Society for Healthcare Epidemiology of America (SHEA) defines AMS as a "set of coordinated strategies to improve the use of antimicrobial medications with the goal to

• enhance patient health outcomes,
• reduce antibiotic resistance, and
• decrease unnecessary costs".[4]

Decreasing the overuse of antimicrobials is expected to serve the following goals:

• improve patient outcomes, especially patient safety
• decrease adverse drug reactions such as hypersensitivity reactions or kidney or heart damage (e.g., QT prolongation).
• decrease antibiotic-associated disease, such as Clostridium difficile–associated diarrhea, other antibiotic-associated diarrheas, and invasive candidiasis
• guard the patient's microbiome, including the gut flora, respiratory tract flora, urogenital tract flora, and skin flora (this is closely related to the preceding goal of preventing antibiotic-associated disease)
• decrease wasted costs
• slow the increase in antimicrobial resistance
• prevent unforeseen environmental degradation, such as likely adverse effects of altering biotas and animal microbiotas by pervading the water cycle with antimicrobials in wastewater

Antimicrobial misuse was recognized as early as the 1940s, when Alexander Fleming remarked on penicillin's decreasing efficacy, because of its overuse.[5]

In 1966, the first systematic assessment of antibiotic use in the Winnipeg, Manitoba, Canada general hospital was published: Medical records were reviewed during two non-consecutive four-month periods (medicine, psychiatry, urology, gynecology and surgery, orthopedics, neurosurgery, ear, nose and throat, and ophthalmology). Information was coded on punched cards using 78 columns.[6] Others in 1968 estimated that 50% of antimicrobial use was either unnecessary or inappropriate [7] This figure is likely the lower end of the estimate, and continues to be referenced as of 2015.

In the 1970s the first clinical pharmacy services were established in North American hospitals. The first formal evaluation of antibiotic use in children regarding antibiotic choice, dose and necessity of treatment was undertaken at The Children's Hospital of Winnipeg. Researchers observed errors in therapy in 30% of medical orders and 63% of surgical orders.[8] The most frequent error was unnecessary treatment found in 13% of medical and 45% of surgical orders. The authors stated "Many find it difficult to accept that there are standards against which therapy may be judged."

In the 1980s the antibiotic class of cephalosporins was introduced, further increasing bacterial resistance. During this decade infection control programs began to be established in hospitals, which systematically recorded and investigated hospital-acquired infections. Evidence-based treatment guidelines and regulation of antibiotic use surfaced. Australian researchers published the first medical guideline outcomes research.

The term AMS was coined in 1996 by two internists at Emory University School of Medicine, John McGowan and Dale Gerding, a specialist on C. difficile. They suggested "...large-scale, well-controlled trials of antimicrobial use regulation employing sophisticated epidemiologic methods, molecular biological organism typing, and precise resistance mechanism analysis [...] to determine the best methods to prevent and control this problem [antimicrobial resistance] and ensure our optimal antimicrobial use stewardship" and that "...the long-term effects of antimicrobial selection, dosage, and duration of treatment on resistance development should be a part of every antimicrobial treatment decision."[9]

In 1997, SHEA and the Infectious Diseases Society of America published guidelines to prevent antimicrobial resistance arguing that "…appropriate antimicrobial stewardship, that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms." [10]

Ten years later, in 2007, bacterial, antiviral and antifungal resistance had risen to such a degree that the CDC rang the alarm . The same year, IDSA and SHEA published guidelines for developing an AMS program.[11] Also in 2007, the first pediatric publication used the term AMS.[12]

A survey of pediatric infectious disease consultants in 2008 by the Emerging Infectious Disease Network revealed that only 45 (33%) respondents had an AMS program, mostly from before 2000, and another 25 (18%) planned an ASP (data unpublished).

In 2012, the SHEA, IDSA and PIDS published a joint policy statement on AMS.[13]

The CDC's NHSN has been monitoring antimicrobial use and resistance in hospitals that volunteer to provide data.[14]

On September 18, 2014, President Barack Obama issued an Executive Order 13676, "Combating Antibiotic-Resistant Bacteria.' This Executive Order charged a Task Force to develop a 5-Year Action Plan that included steps to reduce the emergence and spread of antibiotic-resistant bacteria and ensure continued availability of effective therapies for infections. Improved antimicrobial stewardship is one of the charges of this Executive Order. The Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) was formed in response to this Executive Order.[15][16]

In 2014, the CDC recommended, that all US hospitals have an antibiotic stewardship program.[17]

The Joint Commission has approved regulations which go into effect January 1, 2017 detailing that hospitals should have an Antimicrobial Stewardship team consisting of Infection preventionist(s), Pharmacist(s), and a Practitioner to write protocols and develop projects focused on the appropriate use of antibiotics.[18] Effective January 1, 2020, The Joint Commission has issued a new standard that antimicrobial stewardship requirements will be expanded to ambulatory (outpatient) health care organizations as well.[19]

AMS is needed wherever antimicrobials are prescribed in human medicine, namely in hospitals, outpatient clinics, and long term care institutions, including hospice.

Guidelines for prudent or judicious use in veterinary medicine have been developed by the Canadian Veterinary Medicine Association in 2008.[20] A particular problem is that veterinarians are both prescribers and dispensers. Regulators and the veterinary community in the European Union have been discussing the separation of these activities.[21]

Antimicrobial stewardship focuses on prescribers, be it physician, physician assistant, nurse practitioner, on the prescription and the microorganism, if any. At a hospital, AMS can be organized in the form of an AMS committee that meets monthly. The day-to-day work is done by a core group, usually an infectious disease physician, who may or may not serve in hospital epidemiology and infection control, or/ and a pharmacist, ideally but rarely aided by an information technologist. The entire committee may include physician representatives, who are top antimicrobial prescribers such as physicians in intensive care medicine, Hematology -Oncology, cystic fibrosis clinicians or hospitalists, a microbiologist, a quality improvement (QI) specialist, and a representative from hospital administration. Six infectious diseases organizations, SHEA, Infectious Diseases Society of America, MAD-ID, National Foundation for Infectious Diseases PIDS, and Society of Infectious Disease Pharmacists, published joint guidance for the knowledge and skills required for antimicrobial stewardship leaders.[22]

For an AMS program to be established the institution has to recognize its value. In the US it has become customary to present a business plan to the executive officers of the hospital administration.

The CDC recommends essential components of AMS programs for acute care hospitals, small and critical access hospitals, resource-limited facilities, long-term care facilities, and outpatient facilities.[23]

As of 2014, thirteen internet-based institutional ASP resources in US academic medical centers had been published.[24] An AMS program has the following tasks, in line with quality improvement theory:

The day-to-day work of the core AMS members is to screen patients' medical records for some of the following questions, in order of importance:

• Appropriate antimicrobial choice based on susceptibility, avoiding redundance ?
• Appropriate dose (mg/kg dosing in children) ?
• Appropriate dosing interval according to age, weight and renal function or drug-drug interaction?
• Appropriate deescalation of antimicrobials after culture results are final ?
• Appropriate administration route and feasibility of drug conversion from intravenous to by mouth (PO)?

If the answer is no, the team needs to effectively communicate a recommendation, which may be in person or in the medical record.

Further tasks are:

• Automatic review of the medical record after 72h empiric use, culture results, other laboratory data
• Advise on appropriate duration of antimicrobial therapy
• Annual report to administration, calculation of cost savings if any.

[27][28] Two pediatric infectious disease physicians have suggested to look at the following variables to judge the outcome of AMS interventions:[29]

• Annual pharmacy acquisition costs
• Antibiotic days/1,000 patient days
• Identifying "drug-bug mismatches"
• IV to oral conversion
• Optimal dosing
• Stopping redundant therapy
• Reducing adverse events
• Overall compliance with ASP recommendations

When examining the relationship between an outcome and an intervention, the epidemiological method of time series analysis is preferred, because it accounts for the dependence between time points. A recent global stewardship survey identified barriers to the initiation, development and implementation of stewardship programmes internationally.[30]

• At this time the optimal metrics to benchmark antimicrobial use are still controversial.
• To measure unit of antimicrobials consumed, one can use 'Days Of Therapy' (DOT) or Defined Daily Dose (DDD). The former is more commonly used in the US, the latter is more commonly used in Europe.
• Data source for the use: The electronic medication administration record (eMAR) is the most accurate correlate for doses given, but may be difficult to analyze, because of hold orders and patient refusal, as opposed to administrative or billing data, that may be easier to obtain.
• The question of "appropriateness of use" is probably the most controversial. Appropriate use depends on the local antimicrobial resistance profile and therefore has different regional answers. Merely the "amount" of antibiotics used is no straightforward metric for appropriateness.
• In regard to the most effective AMS intervention, the answer will depend on the size of the institution and the resources available: The system of "prior approval" of antimicrobials by infectious diseases has been used first historically. It is very time- and labor-intensive, and prescribers do not like its restrictive character. Increasingly "post-prescription review" is used.
• Although education consistently shows improvement in participants' knowledge and attitudes, the results do not always translate to better practice.[31][32]

It can be difficult to decide if a clinical syndrome or a particular drug should be targeted for interventions and education. How to best modify prescriber behavior has been the subject of controversy and research. At issue is how feedback is presented to prescribers, individually, in aggregate, with or without peer comparisons, and whether to reward or punish. As long as the best quality metrics for an AMS program are unknown, a combination of antimicrobial consumption, antimicrobial resistance, and antimicrobial and drug resistant organism related mortality are used.[33]

• Antibiotic resistance
• Broad vs narrow-spectrum antibiotics

• Antimicrobial Stewardship: Implementation Tools & Resources Society for Healthcare Epidemiology of America (SHEA)
• Core Elements of Hospital Antibiotic Stewardship Programs CDC
• Antimicrobial Stewardship Project, at the Center for Infectious Disease Research and Policy (CIDRAP), University of Minnesota
• Promoting Antimicrobial Stewardship in Human Medicine Infectious Diseases Society of America (IDSA)
• Surveillance of antimicrobial use WHO
  • Commitments to Responsible Use of Antimicrobials in Humans WHO 13–14 November 2014
• Alliance for the Prudent Use of Antibiotics (APUA), Tufts University Boston, MA
• Protect Antibiotics Toolkit Health Care Without Harm
• Global Resource Action Center for the Environment (GRACE)
• Center for Science in the Public Interest
• Antibiotics in Groundwater Change Bacterial Ecology US Geological Survey, Toxic Substances Hydrology Program]
• Treat Systems Example of a software tool supporting Antimicrobial Stewardship