Antibiotic misuse, sometimes called antibiotic abuse or antibiotic overuse, refers to the misuse or overuse of antibiotics, with potentially serious effects on health. It is a contributing factor to the development of antibiotic resistance, including the creation of multidrug-resistant bacteria, informally called "super bugs": relatively harmless bacteria (such as Staphylococcus , Enterococcus and Acinetobacter ) can develop resistance to multiple antibiotics and cause life-threatening infections. [1]
Antibiotics have been around since 1928 when penicillin was discovered by Alexander Fleming. In the 1980s, antibiotics that were determined medically important for treatment of animals could be approved under veterinary oversight. In 1996, the National Antimicrobial Resistance Monitoring System (NARMS) was established. [2] Starting in 2010, publications regarding antimicrobial drugs in food became an annual report. Starting in 2012, there was publicly solicited input on how data is to be collected and reported for matters relating to the use of antimicrobials for food-producing animals. Resulting from this, the FDA revised its sampling structure within NARMS with the goal of obtaining more representative livestock data for the key organisms under surveillance. [2] "NARMS partners at CDC and USDA have published over 150 peer-reviewed research articles examining the nature and magnitude of antimicrobial resistance hazards associated with antibiotic use in food-producing animals." In 2014, the FDA began working with the United States Department of Agriculture (USDA) and the Centers of Disease Control and Prevention (CDC) to explore additional mechanisms to obtain data that is representative of antibiotic use in food-producing animals. In 2015, the FDA issued the Veterinary Feed Directive (VFD) final rule, under which veterinarians must authorize the use of antimicrobials within feed for the animals they serve. [2]
In addition to antibiotic regulation in food production, there have been numerous policies put in place to regulate antibiotic distribution in healthcare, specifically in hospital settings. In 2014, the CDC officially recognized the need for antimicrobial stewardship within all U.S. hospitals in their publication of the Core Elements of Hospital Antibiotic Stewardship Programs. These programs outline opportunities for reducing unnecessary antibiotic usage, and provide guidelines for antibiotic prescription for common infections. The CDC highlighted post-prescription tactics for antibiotic regulation, such as reassessing dosages and the class or type of antibiotic used, in order to optimally treat each infection. [3] The CDC also emphasized the need for evidence-based prescribing, a practice that focuses on the utilization of evidence and research to make informed medical decisions; [4] these sentiments were echoed by the American Dental Association (ADA) which works to provide detailed guidelines for dentists considering prescribing their patients antibiotics. [5] In 2019, the CDC published a report concerning the issue and updating the public on the effectiveness of past policy. This report, titled Antibiotic Resistance Threats in the United States, 2019, indicated which pathogens posed the greatest threat of resistance, and highlighted the importance of infection prevention, providing recommendations for prevention strategies. [6]
There has also been a substantial effort to educate not only prescribers, but patients too on the issue of antibiotic misuse. The World Health Organization (WHO) has designated a "World Antimicrobial Awareness Week" in November. In 2021, the week's theme was "Spread Awareness, Stop Resistance" and the organization published many different forms of media including podcasts, articles, and infographics to raise awareness for the issue. [7] In the United States, the CDC has published posters and other materials for the purpose of educating the public on antibiotic resistance. [8] State health departments, such as Colorado's Department of Public Health & Environment, have partnered with the CDC to distribute these materials to healthcare providers. [9]
Antibiotics treats bacterial infections rather than viral infections.
Common situations in which antibiotics are overused include the following: [10]
Antibiotics can cause severe reactions and add significantly to the cost of care. [21] In the United States, antibiotics and anti-infectives are the leading cause of adverse effect from drugs. In a study of 32 States in 2011, antibiotics and anti-infectives accounted for nearly 24 percent of ADEs that were present on admission, and 28 percent of those that occurred during a hospital stay. [22]
If antimicrobial resistance continues to increase from current levels, it is estimated that by 2050 ten million people would die every year due to lack of available treatment [23] and the world's GDP would be 2 – 3.5% lower in 2050. [24] If worldwide action is not taken to combat antibiotic misuse and the development of antimicrobial resistance, from 2014 – 2050 it is estimated that 300 million people could die prematurely due to drug resistance and $60 – 100 trillion of economic output would be lost. [24] If the current worldwide development of antimicrobial resistance is delayed by just 10 years, $65 trillion of the world's GDP output can be saved from 2014 to 2050. [24]
Prescribing by an infectious disease specialist compared with prescribing by a non-infectious disease specialist decreases antibiotic consumption and reduces costs. [25]
Though antibiotics are required to treat severe bacterial infections, misuse has contributed to a rise in bacterial resistance. [26] The overuse of fluoroquinolone and other antibiotics fuels antibiotic resistance in bacteria, which can inhibit the treatment of antibiotic-resistant infections. [27] [28] [29] Their excessive use in children with otitis media has given rise to a breed of bacteria resistant to antibiotics entirely. [30] Additionally, the use of antimicrobial substances in building materials and personal care products has contributed to a higher percentage of antibiotic resistant bacteria in the indoor environment, where humans spend a large majority of their lives. [31]
Widespread use of fluoroquinolones as a first-line antibiotic has led to decreased antibiotic sensitivity, with negative implications for serious bacterial infections such as those associated with cystic fibrosis, where quinolones are among the few viable antibiotics. [32] [33] [34]
Antibiotics have no effect on viral infections such as the common cold. They are also ineffective against sore throats, which are usually viral and self-resolving. [35] Most cases of bronchitis (90–95%) are viral as well, passing after a few weeks—the use of antibiotics against bronchitis is superfluous and can put the patient at risk of developing adverse reactions. [36] If you take an antibiotic when you have a viral infection, the antibiotic attacks bacteria in your body, bacteria that are either beneficial or at least not causing disease. This misdirected treatment can then promote antibiotic-resistant properties in harmless bacteria that can be shared with other bacteria, or create an opportunity for potentially harmful bacteria to replace the harmless ones. [37]
Official guidelines by the American Heart Association for dental antibiotic prophylaxis call for the administration of antibiotics to prevent infective endocarditis. Though the current (2007) guidelines dictate more restricted antibiotic use, many dentists [38] and dental patients [39] follow the 1997 guidelines instead, leading to overuse of antibiotics. [40]
A study by Imperial College London in February 2017 found that of 20 online websites, 9 would provide antibiotics (illegally) without a prescription to UK residents. [41]
Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse. [42] [43] Antibiotics should also be used at the lowest dose for the shortest course. For example, research in the UK has shown that a 3-day course of antibiotics (amoxicillin) was as effective as 7-day course for treating children with pneumonia. [44] [45]
There has been significant use of antibiotics in animal husbandry. The most abundant use of antimicrobials worldwide is in livestock; they are typically distributed in animal feed or water for purposes such as disease prevention and growth promotion. [46] Debates have arisen surrounding the extent of the impact of these antibiotics, particularly antimicrobial growth promoters, on human antibiotic resistance. Although some sources assert that there remains a lack of knowledge on which antibiotic use generates the most risk to humans, [47] policies and regulations have been placed to limit any harmful effects, such as the potential of bacteria developing antibiotic resistance within livestock, and that bacteria transferring resistance genes to human pathogens [48] Many countries already ban growth promotion, and the European Union has banned the use of antibiotics for growth promotion since 2006. [49] On 1 January 2017, the FDA enacted legislation to require that all human medically important feed-grade antibiotics (many prior over-the-counter-drugs) become classified as Veterinary Feed Directive drugs (VFD). This action requires that farmers establish and work with veterinaries to receive a written VFD order. [50] The effect of this act places a requirement on an established veterinarian-client-patient relationship (VCPR). Through this relationship, farmers will receive an increased education in the form of advice and guidance from their veterinarian. Resistant bacteria in food can cause infections in humans. Similar to humans, giving antibiotics to food animals will kill most bacteria, but resistant bacteria can survive. When food animals are slaughtered and processed, resistant germs in the animal gut can contaminate the meat or other animal products. Resistant germs from the animal gut can also get into the environment, like water and soil, from animal manure. If animal manure or water containing resistant germs are used on fruits, vegetables, or other produce as fertilizer or irrigation, then this can spread resistant germs. [51]
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the ones which cause the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance to the point that one or more drugs used to fight them are no longer effective. Fungi evolve antifungal resistance, viruses evolve antiviral resistance, protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Together all of these come under the umbrella of antimicrobial resistance.
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken by mouth, as eye drops, as ear drops, or intravenously.
Levofloxacin, sold under the brand name Levaquin among others, is a broad-spectrum antibiotic of the fluoroquinolone drug class. It is the left-handed isomer of the medication ofloxacin. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori, urinary tract infections, Legionnaires' disease, chronic bacterial prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. It is available by mouth, intravenously, and in eye drop form.
Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.
Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken by mouth or injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prostatitis, plague, and certain types of infectious diarrhea. Other uses, along with other medications, include treating multidrug resistant tuberculosis. An eye drop may be used for a superficial bacterial infection of the eye and an ear drop may be used for otitis media when a hole in the ear drum is present.
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites.
Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.
Pefloxacin is a quinolone antibiotic used to treat bacterial infections. Pefloxacin has not been approved for use in the United States.
Multidrug resistant Gram-negative bacteria are a type of Gram-negative bacteria with resistance to multiple antibiotics. They can cause bacteria infections that pose a serious and rapidly emerging threat for hospitalized patients and especially patients in intensive care units. Infections caused by MDR strains are correlated with increased morbidity, mortality, and prolonged hospitalization. Thus, not only do these bacteria pose a threat to global public health, but also create a significant burden to healthcare systems.
Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry, specifically poultry production.
Antibiotics are commonly used in commercial swine production in the United States and around the world. They are used for disease treatment, disease prevention and control, and growth promotion. When used for growth promoting purposes, antibiotics are given at low concentrations for long periods of time. Low concentration of antibiotics, also referred to as subtherapeutic (STA), are given as feed and water additives which improve daily weight gain and feed efficiency through alterations in digestion and disease suppression. Additionally, the use of STA in swine results in healthier animals and reduces the “microbial load” on meat resulting in an assumed decrease in potential Foodborne illness risk. While the benefits of subtherapeutic antibiotic administration are well-documented, there is much concern and debate regarding the development of bacterial antibiotic resistance associated with their use.
Neisseria gonorrhoeae, the bacterium that causes the sexually transmitted infection gonorrhea, has developed antibiotic resistance to many antibiotics. The bacteria was first identified in 1879.
Enzybiotics are an experimental antibacterial therapy. The term is derived from a combination of the words “enzyme” and “antibiotics.” Enzymes have been extensively utilized for their antibacterial and antimicrobial properties. Proteolytic enzymes called endolysins have demonstrated particular effectiveness in combating a range of bacteria and are the basis for enzybiotic research. Endolysins are derived from bacteriophages and are highly efficient at lysing bacterial cells. Enzybiotics are being researched largely to address the issue of antibiotic resistance, which has allowed for the proliferation of drug-resistant pathogens posing great risk to animal and human health across the globe.
Antibiotic use in livestock is the use of antibiotics for any purpose in the husbandry of livestock, which includes treatment when ill (therapeutic), treatment of a group of animals when at least one is diagnosed with clinical infection (metaphylaxis), and preventative treatment (prophylaxis). Antibiotics are an important tool to treat animal as well as human disease, safeguard animal health and welfare, and support food safety. However, used irresponsibly, this may lead to antibiotic resistance which may impact human, animal and environmental health.
Antimicrobial stewardship (AMS) refers to coordinated efforts to promote the optimal use of antimicrobial agents, including drug choice, dosing, route, and duration of administration.
ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. The acronym is sometimes extended to ESKAPEE to include Escherichia coli. This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs, blood, urinary tract, and in other body regions after surgery. S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.
Antimicrobial resistance (AMR) directly kills about 1,600 people each year in Australia. This is a currently serious threat to both humans and animals in the country. Antimicrobial resistance occurs when a microorganism evolves and gains the ability to become more resistant or completely resistant to the medicine that was previously used to treat it. Drug-resistant bacteria are increasingly difficult to treat, requiring replacement or higher-dose drugs that may be more expensive or more toxic. Resistance can develop through one of the three mechanisms: natural resistant ability in some types of microorganisms, a mutation in genes or receiving the resistance from another species. Antibodies appear naturally due to random mutations, or more often after gradual accumulation over time, and because of abuse of antibiotics. Multidrug-resistance, or MDR, are the microorganisms that are resistant to many types of antimicrobials. "Superbugs" is the term also used for multidrug-resistant microbes, or totally drug-resistant (TDR).
Antibiotic use in the United States poultry farming industry is the controversial prophylactic use of antibiotics in the country's poultry farming industry. It differs from the common practice in Europe, where antibiotics for growth promotion were disallowed in the 1950s.
From 1995 to 2002, inappropriate antibiotic prescribing for acute respiratory infections, which are usually caused by viruses and thus are not responsive to antibiotics, declined from 61% to 49%. However, the use of broad-spectrum antibiotics such as the fluoroquinolones, jumped from 41% to 77% from 1995 to 2001. Overuse of these antibiotics will eventually render them useless for treating antibiotic-resistant infections, for which broad-spectrum antibiotics are supposed to be reserved.
Gatifloxacin and moxifloxacin have no proven clinical advantages over other fluoroquinolones, macrolides, or amoxicillin. Based on cost, they are not first-choice drugs for their approved indications.