About this course:
This learning activity aims to provide a comprehensive overview of antimicrobial and antibiotic resistance, including prevalence, drug-resistant organisms, antimicrobial stewardship (AMS) programs, prescribing guidelines, and barriers to appropriate antimicrobial use.
Antimicrobial Resistance for LPNs and RNs
This learning activity aims to provide a comprehensive overview of antimicrobial and antibiotic resistance, including prevalence, drug-resistant organisms, antimicrobial stewardship (AMS) programs, prescribing guidelines, and barriers to appropriate antimicrobial use.
Upon completion of this module, learners will be able to:
- differentiate between antimicrobial and antibiotic resistance
- recognize how microorganisms become drug-resistant
- identify and classify drug-resistant organisms
- generalize the goals and core elements of AMS programs
- explain the barriers to appropriate antimicrobial prescribing
Since their discovery, antimicrobials—especially antibiotics—have effectively treated infections. Antibiotics have decreased the morbidity and mortality that commonly occurred due to bacterial infections before their discovery. Unfortunately, widespread misuse of antimicrobials and inappropriate prescribing habits have led to the emergence of antimicrobial and antibiotic resistance. Antibiotic resistance is considered among the most significant health threats faced in modern times (Agency for Healthcare Research and Quality [AHRQ], 2022; Centers for Disease Control and Prevention [CDC], 2019).
Antibiotic Resistance versus Antimicrobial Resistance
Antimicrobial resistance (AMR) is a broad term that describes what occurs when bacteria, fungi, viruses, and parasites become resistant to the medications used to combat infections such as malaria (parasite), human immunodeficiency virus (HIV; virus), or candida (fungus). According to the World Health Organization (WHO), AMR is in the top 10 most significant threats to global public health. Antibiotic resistance occurs when bacteria mutate in response to antibiotics, making treatment with them ineffective in combatting bacterial infections. AMR and antibiotic resistance intensify the difficulty of treating certain microorganisms, increasing the likelihood of disease spread and patients experiencing adverse outcomes, including mortality (WHO, 2021).
Development of Resistance
Antibiotic resistance occurs when a bacterium evolves and adapts to evade the effects of an antibiotic. This happens through different mechanisms. These changes make treatment with previously effective antibiotics against the bacterium ineffective. This phenomenon is complicated to address since any adaptation is transferred to new bacteria as division occurs. Four categories are commonly used to classify the mechanisms that bacteria use to develop antibiotic resistance (Habboush & Guzman, 2022).
- Intrinsic resistance occurs when bacteria change their structure to evade certain antibiotics. One example of this phenomenon is bacteria that have evolved to survive without a cell wall and are not affected by treatment with penicillin, which works by affecting the wall-building mechanism of bacteria.
- Acquired resistance occurs when a bacterium that was previously susceptible to a particular antibiotic becomes resistant to its effects. This can occur through genetic changes within bacteria or DNA transfer from a bacterium already resistant to the antibiotic. One example of this phenomenon is Mycobacterium tuberculosis (M. TB), which has become resistant to rifamycin (Aemcolo) through chromosomal mutations of the genes required for rifamycin (Aemcolo) prodrug activation.
- Genetic changes occur when bacteria's DNA changes, altering protein production. This changes the components of the bacterium, including receptors, making the bacteria unrecognizable to antibiotics developed to identify that bacterium based on certain identifying factors and attaching to those specific receptors. An example of this phenomenon is the resistance of Escherichia coli (E. coli) and Haemophilus influenzae to trimethoprim (Primsol).
- DNA transfer leads to resistance when bacteria share genetic materials with other bacteria. Resistant DNA can be transferred from one bacterium to another through horizontal gene transfer, leading to resistance in the receiving bacteria. Bacteria can acquire external genetic material in 3 stages: transformation through naked DNA incorporation, transduction through phagocytosis, and conjugation through direct contact. An example of DNA transfer is Staphylococcus aureus (S. aureus), which has become resistant to methicillin (Staphcillin).
The Threat of Resistant Pathogens
The CDC completes an antibiotic-resistant threat report to monitor the effects of antibiotic resistance in the US. The last two reports were released in 2013 and 2019. From 2013 to 2019, the number of deaths caused by antibiotic resistance decreased by 18%, with a 28% decrease in antibiotic-resistant deaths that occurred in a hospital. There was also a decrease in infections caused by vancomycin-resistant Enterococcus (41%), carbapenem-resistant Acinetobacter (33%), multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa, 29%), drug-resistant Candida (25%), and methicillin-resistant S. aureus (MRSA, 21%). Unfortunately, despite these improvements, there have still been over 2.8 million antibiotic-resistant infections and over 35,000 deaths due to antibiotic resistance each year since 2013. In addition to these cases, there have been 223,900 infections and 12,800 deaths from Clostridium difficile (C. difficile) each year. Infections with erythromycin-resistant invasive group A Streptococcus have increased by 315%, drug-resistant Neisseria gonorrhoeae (N. gonorrhoeae) by 124%, and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae by 50% since 2013. Antibiotic resistance can increase the length of hospital stay and healthcare costs. On average, the treatment of antimicrobial-resistant infections is $18,000 to $29,000, with an increase in the length of hospital admission by 6.4 to 12.7 days (AHRQ, 2022; CDC, 2019; Shrestha et al., 2022).
The CDC published a report in 2019 that classifies the threat level of resistant organisms. This report does not include drug-resistant viruses or parasites (CDC, 2019). The threat levels and correlating microorganisms are as follows:
- urgent threat
- carbapenem-resistant Acinetobacter
- Candida auris (C. auris)
- C. difficile
- carbapenem-resistant Enterobacteriaceae (CRE)
- drug-resistant N. gonorrhoeae
- serious threat
- drug-resistant Campylobacter
- drug-resistant Candida
- ESBL-producing Enterobacteriaceae
- vancomycin-resistant Enterococci (VRE)
- multidrug-resistant P. aeruginosa
- drug-resistant nontyphoidal Salmonella
- drug-resistant Salmonella serotype Typhi
- drug-resistant Shigella
- drug-resistant Streptococcus pneumoniae (S. pneumoniae)
- drug-resistant tuberculosis (TB)
- concerning threat
- erythromycin-resistant group A Streptococcus
- clindamycin-resistant group B Streptococcus
- watch list
- azole-resistant Aspergillus fumigatus (A. fumigatus)
- drug-resistant Mycoplasma genitalium (M. genitalium)
- drug-resistant Bordetella pertussis (B. pertussis; CDC, 2019; Shrestha et al., 2022)
Antibiotic Usage Rates
Antibiotic resistance is linked to poor prescribing
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Overprescribing and misusing antibiotics occur primarily in outpatient care settings. Out of all antibiotic prescribing in primary care clinics, emergency departments, and other outpatient settings, 33% of prescriptions are inappropriate, equating to over 47 million prescriptions yearly. The CDC's 2021 outpatient antibiotic prescription report shows prescribing rates for oral antibiotics per 1,000 people. In 2021, over 211.1 million prescriptions were written for antibiotics, equaling 636 prescriptions for every 1,000 people. Individuals under 20 years old were prescribed antibiotics 37.2 million times, equal to a rate of 601 per 1,000 people. Those 20 and older were prescribed antibiotics 173.7 million times, or a rate of 643 per 1,000 people. Females of any age were prescribed antibiotics more frequently than males. Antibiotics were prescribed 130.1 million times at a rate of 777 per 1,000 females compared to 80.7 million times for males at a rate of 491 per 1,000 people. The most common class of antibiotics prescribed is penicillins, with 46.4 million prescriptions and a rate of 140 per 1,000 people, followed by cephalosporins, with 31.4 million prescriptions and a rate of 95 per 1,000 people, then macrolides, with 29.9 million prescriptions and a rate of 90 per 1,000 people, tetracyclines with 25.0 million prescriptions and a rate of 75 per 1,000 people, and B-lactams with 22.6 million prescriptions and a rate of 68 per 1,000 people. Several specific antibiotics are also prescribed more frequently than others. Amoxicillin (Amoxil) is the most commonly prescribed antibiotic, with 42.9 million prescriptions and a rate of 129 per 1,000 people, followed by azithromycin (Zithromax) with 28.7 million prescriptions and a rate of 86 per 1,000 people, then amoxicillin-clavulanic acid (Augmentin) with 22.6 million prescriptions and a rate of 68 per 1,000 people, doxycycline (Vibramycin) with 21.7 million prescriptions and a rate of 65 per 1,000 people, and cephalexin (Keflex) with 20.5 million prescriptions and a rate of 62 per 1,000 people (CDC, 2022; PEW Charitable Trust, 2020).
Prescribing habits and rates of antibiotic use vary based on provider credentials or specialty and geographical location. Advanced practice registered nurses (APRNs) and physician assistants (PAs) prescribe the most antibiotics, with 69.8 million prescriptions at a rate of 403 per 1,000 people, followed by primary care physicians (PCPs) with 61.2 million antibiotic prescriptions and a rate of 258 per 1,000 people. Providers working in different specialties also have varying rates of antibiotic prescribing. Those working in dermatology have the highest rate of antibiotic prescribing with a rate of 505 per 1,000 people, equating to 5.7 million prescriptions, followed by emergency medicine with a prescribing rate of 332 per 1,000 people and 10.7 million prescriptions, dentistry with a rate of 208 per 1,000 people and 25.5 million prescriptions, surgical specialties with a rate of 183 per 1,000 people and 16.3 million prescriptions, and obstetrics and gynecology with a rate of 122 per 1,000 people and 4.6 million prescriptions. All other disciplines not listed prescribed 17.1 million antibiotics with a rate of 82 per 1,000 people. Antibiotic prescribing rates differ between states and geographical regions. The southern US has the highest antibiotic prescribing rate of 756 per 1,000 people, equating to 96.1 million prescriptions, followed by the midwest at a rate of 643 per 1,000 people and 44.3 million prescriptions, the northeast at a rate of 627 per 1,000 people and 35.8 million prescriptions, and lastly the west at a rate of 441 per 1,000 people or 34.7 million prescriptions (CDC, 2022).
Medications and Resistant Organisms
Since penicillin was discovered in 1928 and utilized clinically to treat bacterial infections, bacteria and other microorganisms have been adapting to become resistant to the drugs commonly used to destroy them. Table 1 lists common medications and the organisms that have developed resistance to their use (CDC, 2019).
Antibiotics and Resistant Organisms
Penicillin-resistant S. aureus
Penicillin-resistant S. pneumoniae
Penicillinase-producing N. gonorrhoeae
Plasmid-mediated vancomycin-resistant Enterococcus faecium (E. faecium)
Vancomycin-resistant S. aureus
Amphotericin B (AmBisome)
Amphotericin B-resistant C. auris
ESBL-producing E. coli
Azithromycin-resistant N. gonorrhoeae
Klebsiella pneumoniae (K. pneumoniae) carbapenemase (KPC)-producing K. pneumoniae
Ciprofloxacin-resistant N. gonorrhoeae
Daptomycin-resistant methicillin-resistant S. aureus
Ceftazidime-avibactam-resistant KPC-producing K. pneumoniae
Few new antibiotics are being developed, which further exacerbates the problem of antibiotic resistance. Between 1935 and 2003, 14 new classes of antibiotics were developed and approved for use; however, since 2017, only 11 new antibiotics have been released. This decrease in innovation is attributed to the cost and risk of antibiotic development. Antibiotics are also not as profitable as medications used to treat more common chronic diseases. Due to the lack of new antibiotic alternatives being produced, antibiotic resistance limits treatment options, making antibiotic stewardship essential to decrease the emergence of new drug-resistant organisms with limited alternative treatment options (Shrestha et al., 2022).
Antimicrobial Stewardship Programs
In response to the poor prescribing habits of providers across all patient care settings, the Centers for Medicare and Medicaid Services (CMS), CDC, Society for Healthcare Epidemiology of America (SHE), PEW Charitable Trust, and the Joint Commission (TJC) developed antimicrobial use standards for hospitals, long-term care facilities, and outpatient care settings. CMS also requires all hospitals to have an AMS program in place. RNs must understand their essential role in educating patients on correct antibiotic use when initiating treatment (Shrestha et al., 2022).
Antimicrobial Stewardship Program Goals
AMS programs have established goals to address antimicrobial resistance (Shrestha et al., 2022). The goals are outlined as follows:
- educate providers on the 5 Ds of antimicrobial use:
- the right drug
- the right dose
- the right drug-route
- the right treatment duration
- timely de-escalation to a pathogen-specific treatment based on culture results
- prevent the overuse and inappropriate use of antimicrobials in various clinical settings, including hospitals, outpatient clinics, and the community
- reduce the prevalence of antibiotic-related secondary infections (e.g., C. difficile)
- minimize the emergence of new resistant organisms
- improve patient outcomes
- reduce healthcare spending on the treatment of infections with resistant organisms (Shrestha et al., 2022)
In addition to the AMS program goals, there are associated core elements of AMS programs that must be present (CDC, 2021a; Shrestha et al., 2022).
- Leadership commitment: for AMS programs to be successful, there must be leadership support. Leaders can show their commitment by championing the development and implementation of practice changes. Leaders should also act as a point of contact for the chair of the AMS program to troubleshoot obstacles, facilitate relationships, and provide additional resources as needed. Regular meetings should be held between the organizational leadership and the AMS program leadership to discuss progress, barriers, and expectations. Organizational leadership can also support AMS programs by including language in job expectations that demonstrate the individual responsibility to participate in AMS. Leadership also can bring together other departments that can support the AMS program, including providers, pharmacy, infection prevention and control, quality improvement, microbiology, information technology, and nursing.
- Accountability and drug expertise: institutions must appoint an AMS program leader, or co-leaders, who will take responsibility and accountability for the program. Having a designated leader increases the success rate of the program. Often, having an infectious disease physician experienced with AMS programs and a clinical pharmacist as co-leaders improves the success rate of newly implemented AMS programs. A 2019 NHSN hospital survey determined that physicians and pharmacists co-led 59% of hospital AMS programs. If the leader is not a prescriber, it is essential that an individual that does have prescribing capabilities be appointed to support the leader and act as a point of contact on behalf of the medical staff. Pharmacists have the drug knowledge to support and lead the implementation of the stewardship program. Pharmacists can facilitate appropriate prescribing by verifying true medication allergies, avoiding duplication of antimicrobial coverage, reassessing the need for antimicrobial treatment, avoiding the treatment of certain infections such as asymptomatic bacteriuria, and ensuring that treatment is given for the shortest duration possible while maintaining effectiveness.
- Action: for an AMS program to succeed, new policies and procedures must be implemented to optimize appropriate antibiotic use. Some of these policies include:
- incorporating a requirement that antibiotic use must be reassessed after 48 hours of initiation to ensure the appropriateness of the medication being used
- utilizing pharmacists for dosing modifications based on laboratory testing to measure drug levels and organ function (i.e., hepatic and renal)
- creating infection-specific prescribing protocols that are based on community infection data regarding common strains of infection (e.g., community-acquired pneumonia)
- Tracking and reporting: tracking antibiotic prescribing habits can help determine whether prescribers are following diagnostic guidelines and policies for antibiotic use. Further education may be indicated based on antibiotic use monitoring results.
- Education: frequent education is required to keep prescribers updated on changes in prescribing practices, emerging antibiotic-resistant organisms, and the management of infectious diseases.
Antibiotic Stewardship Programs
One aspect of AMS is the appropriate use of antibiotics to address antibiotic resistance. Antibiotic stewardship programs have been used in hospitals and outpatient care settings to address antibiotic resistance (CDC, 2021a, 2021b).
Hospital Antibiotic Stewardship Programs
Hospital antibiotic stewardship programs follow the same guidelines and are composed of the same elements and goals as hospital AMS programs. The only difference is that AMS programs encompass preventing resistance to viruses, parasites, fungi, and bacteria, while antibiotic stewardship programs focus on preventing bacterial resistance to antibiotics (CDC, 2021a).
Outpatient Antibiotic Stewardship Programs
Outpatient antibiotic stewardship programs focus on improving antibiotic prescribing habits in primary care clinics, emergency departments, urgent care clinics, dental offices, and ambulatory specialty medical offices and care centers. There are four core elements of outpatient antibiotic stewardship programs that act as a framework for changing the use of antibiotics (CDC, 2021b). These core elements are:
- commitment: demonstrate a dedication to improving prescribing practices and adherence to best practice guidelines
- action for policy and practice: implement policy and procedures that set guidelines aimed at improving antibiotic prescribing practices
- tracking and reporting: monitor antibiotic prescribing and provide education and constructive feedback to improve prescribing practices
- education and expertise: provide education to providers to optimize antibiotic use and prevent resistance (CDC, 2021b)
The initial step in implementing an antibiotic stewardship program is identifying the conditions that providers most frequently treat with antibiotics either inappropriately or ineffectively. This includes prescribing the wrong drug, dose, or duration; underprescribing; or overprescribing. Conditions that cause this phenomenon are known as high-priority conditions due to their impact on antibiotic resistance. Conditions that providers frequently overprescribe antibiotics to treat include viral pharyngitis, acute bronchitis, and non-specific respiratory infections. A condition that is frequently diagnosed and treated with antibiotics even when the diagnostic criteria are not met is streptococcal pharyngitis, which is often diagnosed and treated without testing for group A Streptococcus. Underprescribing commonly occurs in the case of sexually transmitted infections (STIs), which are often not diagnosed and treated promptly. Antibiotics are commonly prescribed for acute otitis media (AOM) or uncomplicated sinusitis despite the best practice being to take a watch-and-wait approach (CDC, 2021b).
Once high-priority conditions are identified, program leaders should determine why best practices regarding antibiotic use and disease management are not followed. Causes include a lack of knowledge of the providers on clinical guidelines, wanting to meet patient expectations regarding treatment options and increase their satisfaction, and the pressure from management to see too many patients per day, limiting the time spent diagnosing and treating each patient. To address these barriers, healthcare facilities should establish prescribing guidelines based on established best practices based on patient presentation and diagnostic guidelines (CDC, 2021b).
Outpatient Treatment Guidelines
Treatment recommendations are published on prescribing antibiotics appropriately in outpatient settings. These guidelines take into consideration patient presentation, including assessment findings and symptoms. Based on the clinical data, appropriate treatment options are outlined for providers to follow (CDC, 2017a, 2017b).
Barriers to Antibiotic Stewardship
Many clinical barriers must be overcome to implement stewardship programs and improve prescribing habits (CDC, 2019). These barriers include:
- a lack of personal recognition of poor prescribing: when polled, 60% of prescribers believed that they prescribed antimicrobials more appropriately than their peers and therefore did not have any reason to improve their prescribing habits
- pressure from patients to prescribe antimicrobials despite best practices: 47% of providers reported feeling moderate pressure, and 37% felt high to very high pressure from their patients to prescribe antibiotics even when not clinically indicated
- situational factors such as the day of the week: on Fridays, there are limited resources, as any tests run may not result by the time the office closes, or the wait-and-see approach may require intervention over the weekend when the office is not open
- lack of time to participate in AMS education or educate patients on the difference between viral infections and bacterial infections
- inconsistent implementation of CDC recommendations when encountering communicable diseases, such as maintaining isolation precautions
- poor hygiene practices that increase the spread of communicable diseases between patients using healthcare providers (HCPs) as carriers (CDC, 2019; Jeffs et al., 2020; PEW Charitable Trust, 2020)
HCPs should educate community members on how they can assist in the reduction of unnecessary antibiotic use leading to resistance (WHO, 2020). Individuals can help address the growing issue of antibiotic resistance by:
- only taking antibiotics when they are prescribed to them by an HCP for their specific illness and never taking antibiotics prescribed to another individual or leftover antibiotics from a previous illness
- refraining from demanding a specific treatment when seeking medical attention for an illness
- utilizing antibiotics as prescribed and following all instructions for administration (i.e., dietary considerations and duration of treatment; WHO, 2020)
Tools to Combat Resistance
The CDC and public health departments have specific tests that can be used to determine antibiotic resistance to select effective treatment against the organism. Most of these tests are effective but have a high cost and are time-consuming to perform. These tests also cannot distinguish between an infection caused by fungi or bacteria and a viral infection or identify emerging markers for drug resistance. Information on the organism's resistance could facilitate more specific treatment for patients in less time, leading to improved patient outcomes (CDC, 2019).
Vaccines are used to prevent primary infections, which can decrease the risk of subsequent infections and antibiotic use. When the WHO increased the number of pneumococcal conjugate vaccines administered to children, the rate of infection with S. pneumoniae—including resistant strains—decreased. This reduced the annual number of deaths related to S. pneumoniae by 250,000. Pneumonia caused by resistant bacteria, such as MRSA, is the leading cause of morbidity and mortality in patients diagnosed with the flu. Vaccinating against the flu decreases the prevalence of bacterial pneumonia. Vaccinating livestock destined for human consumption has also been shown to decrease the prevalence of particular infections in people. The vaccination of poultry against Salmonella typhimurium has decreased the incidence of Salmonella infections in people. Unfortunately, developing and distributing an effective vaccine is a lengthy and costly process (CDC, 2019).
Antibodies can be administered to infected individuals to provide an immediate immune response to a foreign organism. Antibody-based treatment has been developed to target infection with C. difficile and bacterial-associated pneumonia (CDC, 2019).
Bacteriophages are viruses that can enter and replicate within a bacterium. Researchers have utilized this process and genetically modified phages to kill specific bacteria. Patients in critical condition due to infection with a multidrug-resistant organism have fully recovered after the administration of engineered phages. Further use in patients with severe burns, infection of a left ventricular assist device (LVAD), endocarditis, or bacteremia is being researched. Unfortunately, bacteria may become resistant to phages, requiring a change in the phage therapy utilized (CDC, 2019).
Fecal Microbiota Transplant or Live Biotherapeutics
Fecal microbiota transplant (FMT) or live biotherapeutics (LB) have been used to restore healthy microbes to a digestive tract that has had the normal flora colonized for any reason. This includes damage that occurs following the use of antibiotics. The introduction of beneficial bacteria can help prevent infection with C. difficile and decrease the length of infection with a resistant organism (CDC, 2019).
Agency for Healthcare Research and Quality. (2022). AHRQ safety program for improving antibiotic use: Final report. US Department of Health and Human Services. https://www.ahrq.gov/sites/default/files/wysiwyg/antibiotic-use/overall-antibiotic-stewardship-project-final-report.pdf
Centers for Disease Control and Prevention. (2017a). Adult outpatient treatment recommendations. US Department of Health and Human Services. https://www.cdc.gov/antibiotic-use/clinicians/adult-treatment-rec.html
Centers for Disease Control and Prevention. (2017b). Pediatric outpatient treatment recommendations. US Department of Health and Human Services. https://www.cdc.gov/antibiotic-use/clinicians/pediatric-treatment-rec.html
Centers for Disease Control and Prevention. (2019). Antibiotic threats in the United States, 2019. US Department of Health and Human Services. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
Centers for Disease Control and Prevention. (2021a). Core elements of hospital antibiotic stewardship programs. US Department of Health and Human Services. https://www.cdc.gov/antibiotic-use/core-elements/hospital.html
Centers for Disease Control and Prevention. (2021b). Core elements of outpatient antibiotic stewardship. US Department of Health and Human Services. https://www.cdc.gov/antibiotic-use/core-elements/outpatient.html
Centers for Disease Control and Prevention. (2022). Outpatient antibiotic prescriptions - United States, 2021. US Department of Health and Human Services. https://www.cdc.gov/antibiotic-use/data/report-2021.html
Habboush, Y., & Guzman, N. (2022). Antibiotic resistance. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK513277
Jeffs, L., McIsaac, W., Zahradnik, M., Senthinathan, A., Dresser, L., McIntyre, M., Tannenbaum, D., Bell, C., & Morris, A. (2020). Barriers and facilitators to the uptake of an antimicrobial stewardship program in primary care: A qualitative study. PLOS One, 15(3), e0223822. https://doi.org/10.1371/journal.pone.0223822
PEW Charitable Trust. (2020). National survey reveals barriers to outpatient antibiotic stewardship efforts: Physicians don't recognize their own inappropriate prescribing, are skeptical of some stewardship strategies. https://www.pewtrusts.org/en/research-and-analysis/issue-briefs/2020/08/national-survey-reveals-barriers-to-outpatient-antibiotic-stewardship-efforts
Shrestha, J., Zahra, F., & Cannady, P., Jr. (2022). Antimicrobial stewardship. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK572068
World Health Organization. (2020). Antibiotic resistance: Key facts. https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance
World Health Organization. (2021). Antimicrobial resistance. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance