Antimicrobial resistance (AMR) is the reduced effectiveness of an antibiotic, antimalarial, antifungal, or antiviral prescription medication in treating microorganisms that were previously sensitive to the drug in question. AMR results from the overuse or misuse of antimicrobial agents and emerges as a public health problem when pathogens mutate or develop genetic resistance to these agents.
Antimicrobial resistance is a worldwide problem that affects both sexes, all age groups, and all races. In the United States, between 5% and 10% of all hospital inpatients develop nosocomial infections each year. The number of patients who have died from such infections rose from 13,300 in 2002 to 99,000 in 2013.
Worldwide, multidrug resistant tuberculosis (MDR-TB) caused at least 240,000 deaths in 2016 according to the World Health Organization (WHO). Other diseases that are becoming increasingly resistant to standard treatments include HIV infection, malaria, and gonorrhea. Those at greatest risk include persons with weakened immune systems, those who have had organ transplants, and men who have sex with men.
Antimicrobial resistance is the end result of a combination of natural processes and human behaviors, including the misuse of antimicrobial drugs.
Biological causes of antimicrobial resistance include:
Human behaviors responsible for antimicrobial resistance include the overuse and misuse of antimicrobials:
Microbes have several different mechanisms for resisting antimicrobial drugs:
Mycobacterium tuberculosis. M. tuberculosis is a bacterium that causes tuberculosis, a severe infection that may affect other organs as well as the lungs. It usually requires treatment with a six-month course of antibiotics. Multidrug-resistant tuberculosis (MDRTB) is a form of the disease caused by strains of M. tuberculosis that are resistant to rifampin and isoniazid, the most common antibiotics used to treat TB. MDR-TB requires up to two years of therapy with other antibiotics. Extensively drug-resistant TB (XDR-TB) is resistant to treatment with kanamycin, amikacin, or capreomycin as well as rifampin and isoniazid, and is extremely challenging to treat.
Neisseria gonorrhoeae. N. gonorrhoeae, or the gonococcus, is the bacterium responsible for gonorrhea, a sexually transmitted infection (STI). Gonorrhea is the second most common STI in the United States as of 2018. The gonococcus has proved to be unusually competent in developing drug resistance through gene transfer and the use of an efflux pump to prevent antibiotics from entering its cell wall. At present, gonorrhea is usually treated with a combination of two antibiotics, a cephalosporin and either doxycycline or azithromycin. There is evidence, however, that N. gonorrhoeae is becoming increasingly resistant to all known antibiotics. The first case of a so-called “superbug” form of gonorrhea was diagnosed in a prostitute in Japan in 2009. In June 2012, the World Health Organization (WHO) issued a warning that strains of the gonococcus resistant to cephalosporins are now present worldwide.
Enterococcus faecalis. E. faecalis is a gram-positive bacterium that lives in the digestive tracts of humans and other animals. It is also commonly found in root canal-treated teeth. Multidrug-resistant E. faecalis is often found in hospitals, where it can produce life-threatening meningitis and bacteremia as well as urinary tract infections. Penicillin resistance was first noted in E. faecalis in 1983, vancomycin resistance in 1987, and linezolid resistance in the 1990s.
Pseudomonas aeruginosa. P. aeruginosa is a pathogen with a high level of resistance to antibiotics due to its frequent mutations, frequent gene transfers, and the low permeability of its cell wall. Pseudomonas infections are common in hospitals because the bacterium can live in or on hospital equipment, including urinary catheters. It is also a frequent cause of lung infections in patients with cystic fibrosis. Pseudomonas infections are also often spread by hospital workers with poor hand hygiene.
Clostridium difficile. C. difficile is a gram-positive bacterium that causes diarrheal disease, most often in patients whose normal intestinal flora have been altered by the administration of antibiotics for other illnesses. Diarrhea caused by C. difficile is common in hospitals around the world. The first outbreaks of clindamycin-resistant C. difficile diarrhea first occurred in hospitals in the United States in 1989. The most effective treatments for this bacterium are to discontinue the antibiotics that were first given to the patient, or to administer vancomycin.
Escherichia coli. E. coli is the most common single cause of urinary tract infections. A rod-shaped bacterium that lives in the digestive tract, it can cause disease through food contamination; many food product recalls have involved E. coli. Some virulent strains of E. coli are responsible for bacterial pneumonia, hemolytic-uremic syndrome, peritonitis, and meningitis in newborns. Fluoroquinolone-resistant strains of the bacterium have been present in the United States since 1993.
The effects of antimicrobial resistance on public health include stepped-up concern for preventive measures in underdeveloped countries that include relieving overcrowding, ensuring supplies of clean water, and improving sanitation measures. Stronger governmental oversight of access to antibiotics and better surveillance of outbreaks of infectious disease would also be beneficial.
Another public health measure that has been suggested is the establishment of an international action network that would track antibiotic resistance around the world, thus allowing public health workers to identify trends and determine whether education programs and other preventive measures are effective.
Some infectious diseases, such as influenza, can be prevented by administration of vaccines. Flu vaccines, however, must be modified each year because the flu virus mutates so rapidly. Vaccines against S. aureus are theoretically possible, but are still in the research and development stage as of 2018.
Phage therapy refers to the use of bacteriophages—viruses that infect bacteria—to treat bacterial infections. The bacteriophage destroys the bacterium by binding to it and injecting its own genetic material into the bacterium. This process disrupts the bacterium's normal cell processes and forces it to make new virus particles. First used in the former Soviet Union in the 1920s, phage therapy has not been used in the West since the 1930s. The reasons for its disuse have to do with the unavailability of Russian research in the West during the Cold War, and the discovery and increasing use of antibiotics to treat bacterial infections after World War II.
An order of prohibition is an official government action prohibiting the use of a certain drug or class of drugs in animals in order to slow down the development of antimicrobial resistance and preserve the effectiveness of the drug(s) in treating humans. In September 2005, the FDA banned the use of fluoroquinolones in poultry because of the emergence of fluoroquinolone-resistant strains of Campylobacter in humans. These strains were associated with consumption of poultry meat. On April 6, 2012, the Food and Drug Administration's ban on the use of cephalosporins in cattle, swine, chickens, and turkeys went into effect. The order of prohibition applies to the use of cephalosporins used for the treatment of disease in humans or household pets to prevent or treat disease in farm animals.
Human behavioral changes, including limiting the use of existing antibiotics to treat minor illnesses; educating people about the ineffectiveness of antibiotics in treating viral infections; being more careful about hand hygiene at home as well as in hospitals; reducing the use of antibiotics in agriculture; and practicing safe sex to reduce the spread of drug-resistant gonorrhea as well as other STIs, would all help to minimize antimicrobial resistance.
See also Escherichia coli; HIV/AIDS; Tuberculosis.
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World Health Organization (WHO), Avenue Appia 20, Geneva, Switzerland, 1211 Geneva 27, +41 22 791 21 11, Fax: +41 22 791 31 11, http://www.who.int/en/ .
Rebecca J. Frey, PhD