Antimicrobial stewardship is the systematic effort to educate and persuade prescribers of
antimicrobials to follow
evidence-based
Evidence-based practice (EBP) is the idea that occupational practices ought to be based on scientific evidence. While seemingly obviously desirable, the proposal has been controversial, with some arguing that results may not specialize to indivi ...
prescribing, in order to stem
antimicrobial overuse, and thus
antimicrobial resistance. AMS has been an organized effort of
specialists in
infectious diseases
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
, both in Internal Medicine and Pediatrics with their respective peer-organizations,
hospital pharmacists, the
public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the det ...
community and their professional organizations since the late 1990s. It has first been implemented in hospitals. In the U.S., within the context of physicians' prescribing freedom (choice of
prescription drug
A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
s), AMS had largely been voluntary
self-regulation
Self-regulation may refer to:
*Emotional self-regulation
*Self-control, in sociology/psychology
*Self-regulated learning, in educational psychology
*Self-regulation theory (SRT), a system of conscious personal management
*Industry self-regulation, ...
in the form of policies and appeals to adhere to a prescribing self-discipline until 2017, when the
Joint Commission prescribed that hospitals should have an Antimicrobial Stewardship team, which was expanded to the outpatient setting in 2020.
As of 2019, California and Missouri had made AMS programs mandatory by law.
Definition and goals
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
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
, and
* decrease unnecessary costs".
Decreasing the overuse of antimicrobials is expected to serve the following goals:
* improve patient outcomes, especially
patient safety
Patient safety is a discipline that emphasizes safety in health care through the prevention, reduction, reporting and analysis of error and other types of unnecessary harm that often lead to adverse patient events. The frequency and magnitude of a ...
* 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
Invasive candidiasis is an infection (candidiasis) that can be caused by various species of ''Candida'' yeast. Unlike ''Candida'' infections of the mouth and throat (oral candidiasis) or vagina ( ''Candidal'' vulvovaginitis), invasive candidias ...
* guard the patient's
microbiome
A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably well ...
, including the
gut flora
Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut mi ...
, respiratory tract flora,
urogenital tract flora, and
skin flora
Skin flora, also called skin microbiota, refers to microbiota (communities of microorganisms) that reside on the skin, typically human skin.
Many of them are bacteria of which there are around 1,000 species upon human skin from nineteen phyla.P ...
(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
Environmental degradation is the deterioration of the environment (biophysical), environment through depletion of resources such as quality of air, water and soil; the destruction of ecosystems; habitat destruction; the extinction of wildlife; an ...
, such as likely adverse effects of altering
biotas and animal
microbiota
Microbiota are the range of microorganisms that may be commensal, symbiotic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found t ...
s by pervading the
water cycle
The water cycle, also known as the hydrologic cycle or the hydrological cycle, is a biogeochemical cycle that describes the continuous movement of water on, above and below the surface of the Earth. The mass of water on Earth remains fairly cons ...
with antimicrobials in
wastewater
History
Antimicrobial misuse was recognized as early as the 1940s, when
Alexander Fleming
Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish physician and microbiologist, best known for discovering the world's first broadly effective antibiotic substance, which he named penicillin. His discovery in 1928 of w ...
remarked on penicillin's decreasing efficacy, because of its
overuse.
In 1966, the first systematic assessment of antibiotic use in the
Winnipeg
Winnipeg () is the capital and largest city of the province of Manitoba in Canada. It is centred on the confluence of the Red and Assiniboine rivers, near the longitudinal centre of North America. , Winnipeg had a city population of 749,6 ...
, 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.
Others in 1968 estimated that 50% of antimicrobial use was either unnecessary or inappropriate. 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
The Children's Hospital of Winnipeg is a children's hospital in Winnipeg, Manitoba. It is located on the campus of the Health Sciences Centre near downtown Winnipeg and is expressly devoted to the health care of children.
History
The hospital ...
. Researchers observed errors in therapy in 30% of medical orders and 63% of surgical orders. 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
The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''.
Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...
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
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care practi ...
outcomes research Outcomes research is a branch of public health research which studies the end results ( outcomes) of the structure and processes of the health care system on the health and well-being of patients and populations. According to one medical outcomes an ...
.
The term AMS was coined in 1996 by two
internists at
Emory University School of Medicine
The Emory University School of Medicine is the graduate medical school of Emory University and a component of Emory’s Robert W. Woodruff Health Sciences Center. Before it was established as the Emory School of Medicine in 1915, the school fi ...
, John McGowan and Dale Gerding, a specialist on
C. difficile
''Clostridioides difficile'' ( syn. ''Clostridium difficile'') is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as ''C. difficile'', or ''C. diff'' (), is Gram-positive spe ...
. 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
ntimicrobial resistanceand 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."
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."
Ten years later, in 2007, bacterial, antiviral and antifungal resistance had risen to such a degree that the
CDC
The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency, under the United S ...
rang the alarm . The same year, IDSA and SHEA published guidelines for developing an AMS program. Also in 2007, the first pediatric publication used the term AMS.
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 (ASP), 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.
The CDC's NHSN has been monitoring antimicrobial use and resistance in hospitals that volunteer to provide data.
On September 18, 2014, President
Barack Obama
Barack Hussein Obama II ( ; born August 4, 1961) is an American politician who served as the 44th president of the United States from 2009 to 2017. A member of the Democratic Party, Obama was the first African-American president of the U ...
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 AMS 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.
In 2014, the CDC recommended, that all US hospitals have an antibiotic stewardship program (ASP).
On January 1, 2017
Joint Commission regulations went into effect detailing that hospitals should have an AMS team consisting of infection preventionist(s), pharmacist(s), and a practitioner to write protocols and develop projects focused on the appropriate use of antibiotics. Effective January 1, 2020, the Joint Commission antimicrobial stewardship requirements were expanded to
outpatient health care organizations as well. In 2018, a survey of AMS programs in the US showed each 0.50 increase in pharmacist and physician
full-time equivalent
Full-time equivalent (FTE), or whole time equivalent (WTE), is a unit that indicates the workload of an employee, employed person (or student) in a way that makes workloads or class loads comparable across various contexts. FTE is often used to me ...
support predicted a roughly 1.5-fold increase in the programs effectiveness. but in a 2019 survey 45% of responding physicians reported that their institution provided no support for their ASP services.
Locations
AMS is needed wherever antimicrobials are prescribed in human medicine, namely in acute care hospitals, outpatient clinics, and
long-term care institutions, including
hospice
Hospice care is a type of health care that focuses on the palliation of a terminally ill patient's pain and symptoms and attending to their emotional and spiritual needs at the end of life. Hospice care prioritizes comfort and quality of life by ...
.
Guidelines for prudent or judicious use in
veterinary medicine
Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...
have been developed by the Canadian Veterinary Medicine Association in 2008. A particular problem is that veterinarians are both prescribers and dispensers. As of 2012, regulators and the
Federation of Veterinarians of Europe
The Federation of Veterinarians of Europe (FVE) is a non-profit umbrella organisation of veterinary organisations from 38 European countries. It was founded in 1975 and nowadays represents around 200,000 European veterinarians. The FVE strives to ...
had been discussing the separation of these activities.
Participants
Antimicrobial stewardship focuses on prescribers, be it
physician
A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...
,
physician assistant
A physician assistant or physician associate (PA) is a type of Mid-level practitioner, mid-level health care provider. In North America PAs may diagnose illnesses, develop and manage treatment plans, prescribe medications, and may serve as a pri ...
,
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 an infectious diseases or antimicrobial certified pharmacist, ideally but rarely aided by an information technologist. In most cases, both the infectious diseases physician and the infectious diseases pharmacist co-chair the AMS committee and both serve as the directors and champions of the AMS program and committee. The entire committee may include physician representatives, who are top antimicrobial prescribers such as physicians in
intensive care medicine,
Hematology
Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the produc ...
-
Oncology
Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...
,
cystic fibrosis
Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...
clinicians or
hospitalist
Hospital medicine is a medical specialty that exists in some countries as a branch of family medicine or internal medicine, dealing with the care of acutely ill hospitalized patients. Physicians whose primary professional focus is caring for ho ...
s, a
microbiologist
A microbiologist (from Ancient Greek, Greek ) is a scientist who studies microscopic life forms and processes. This includes study of the growth, interactions and characteristics of Microorganism, microscopic organisms such as bacteria, algae, f ...
, 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
The National Foundation for Infectious Diseases (abbreviated NFID) is a 501(c)(3) non-profit organization dedicated to educating the public and medical community about infectious diseases. It was established in 1973 and is based in Bethesda, Mar ...
PIDS, and
Society of Infectious Disease Pharmacists, published joint guidance for the knowledge and skills required for antimicrobial stewardship leaders.
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
A business plan is a formal written document containing the goals of a business, the methods for attaining those goals, and the time-frame for the achievement of the goals. It also describes the nature of the business, background information on t ...
to the executive officers of the hospital administration.
AMS program components
In the US, the
CDC
The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency, under the United S ...
recommends essential components of AMS programs (ASP) for acute care hospitals, small and critical access hospitals, resource-limited facilities, long-term care facilities, and outpatient facilities.
As of 2014, thirteen internet-based institutional ASP resources in US academic medical centers had been published. An ASP has the following tasks, in line with
quality improvement
Quality management ensures that an organization, product or service consistently functions well. It has four main components: quality planning, quality assurance, quality control and quality improvement. Quality management is focused not only ...
theory:
Baseline assessment
Parts of the baseline assessment are to:
*Measure baseline antimicrobial use, dosing, duration, costs and use patterns.
*Study type of microbial isolates, susceptibilities, and trends thereof
*Identify clinician
indication
Indication may refer to:
* A synonym for sign
* Human interface, highlighting the single object pointed to as a cursor is moved, without any other user action such as clicking, is indication
* Indication (medicine). A valid reason to use a certain ...
for prescriptions.
In hospitals and clinics using electronic medical records, information technology resources are crucial to focusing on these questions. As of 2015, commercial computer surveillance software programs for microbiology and antimicrobial administrations appear to outnumber "homegrown" institutional programs, and include, but are not limited to TREAT Steward, TheraDoc, Sentri7, and Vigilanz.
Goals of desirable antimicrobial use
For the desired antimicrobial use, goals need to be formulated:
*Define "appropriate", rational antimicrobial use for the institution, individual patient units, and define empiric treatment versus culture-directed antimicrobial treatment.
*Establish treatment guidelines for clinical syndromes. These can be disseminated in the form of memos, in-services or grand rounds and may be most effective in the form of decision-making tools at the point of ordering the prescription.
Interventions on antimicrobial prescribing
The actual interventions on antimicrobial prescribing consist of numerous elements
Provide feedback, continuing education
*Survey prescriber knowledge about antibiotics, antifungal or antiviral drugs.
*Provide targeted education about particular antibiotics, or one specific antimicrobial at a time, as well as empiric treatment for syndromes versus culture directed treatment.
*Assist in making duration more visible to prescribers. Some institutions use automatic stop orders.
*Decreasing diagnostic uncertainty by appropriate testing, including rapid diagnostic methods. The most effective strategy to decrease diagnostic uncertainty would be to align the focus with other safety projects, and QI measures (e.g. blood management, adverse effects etc.).
Biomerieux has published case studies of countries that introduced AMS.
Interventions
The day-to-day work of the core AMS members is to screen patients'
medical records in a prospective audit 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.
Outcomes to measure
In 2010, two pediatric infectious disease physicians suggested to look at the following variables to judge the outcome of AMS interventions:
* 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 review of 825 studies evaluating any AMS intervention in a community or hospital setting revealed a low overall quality of antimicrobial stewardship studies, most not reporting clinical and microbiological outcome data.
A 2014 global stewardship survey identified barriers to the initiation, development and implementation of stewardship programmes internationally.
Controversies
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
The defined daily dose (DDD) is a statistical measure of pharmaceutical drug, drug consumption, defined by the World Health Organization (WHO) Collaborating Centre for Drug Statistics Methodology. It is defined in combination with the Anatomical T ...
(DDD). The former is more commonly used in the US, the latter is more commonly used in Europe.
*Data source for antimicrobial use: Where available, the electronic
Medication Administration Record (eMAR) is the most accurate correlate for doses given, but it may be difficult to analyze, because of hold orders and patient refusal, as opposed to administrative data or pharmacy billing data, which 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 disease or pharmacology consultants 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.
*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.
*Although education consistently shows improvement in participants' knowledge and attitudes, the results do not always translate to better AMS practice.
*Unintended consequences of antimicrobial stewardship programs may include disagreement of infectious disease specialists with colleagues, jeopardizing provider autonomy and provider efficiency.
See also
*
Antibiotic resistance
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
*
Broad vs narrow-spectrum antibiotics
References
{{Reflist, 30em
External links
Antimicrobial Stewardship: Implementation Tools & ResourcesSociety for Healthcare Epidemiology of America (SHEA)
CDC
Antimicrobial Stewardship Project at the
Center for Infectious Disease Research and Policy (CIDRAP), University of Minnesota
Promoting Antimicrobial Stewardship in Human MedicineInfectious Diseases Society of America (IDSA)
Surveillance of antimicrobial useWHO
Commitments to Responsible Use of Antimicrobials in HumansWHO 13–14 November 2014
Alliance for the Prudent Use of Antibiotics (APUA) Tufts University Boston, MA
Protect Antibiotics ToolkitHealth Care Without Harm
Global Resource Action Center for the Environment (GRACE)Antibiotics in Our Food System
US Geological Survey, Toxic Substances Hydrology Program Antibiotics in Groundwater Change Bacterial Ecology
Preserve Antibiotics.orgThe Clinician Champions in Comprehensive Antibiotic Stewardship (CCCAS) Collaborative
Treat SystemsCommercial software tool supporting Antimicrobial Stewardship, Denmark
Antimicrobial resistance
Health care quality