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Salem Health: Infectious Diseases & Conditions, 2nd Edition

Antibiotic resistance

by Nicole M. Van Hoey, , Pharm.D.

Category: Treatment

Also known as: Antimicrobial resistance, bacterial resistance, drug resistance

Common Bacteria Resistant to Antibiotics, with Associated Infections

  • Bacillus anthracis (anthrax)

  • Enteroccocci (vancomycin-resistant enterococci infections)

  • Group B Streptococcus (group B strep)

  • Klebsiella pneumoniae (klebsiella infections)

  • Mycobacterium tuberculosis (tuberculosis)

  • Neisseria gonorrhoeae (gonorrhea)

  • Neisseria meningitidis (bacterial meningitis)

  • Salmonella typhi (typhoid fever)

  • Shigella (shigellosis)

  • Staphylococcus aureus (Methicillin-resistant staph infections)

  • Streptococcus pneumoniae (various infections)

Definition

Microbes, typically bacteria, change and resist the activity of antibiotic Antibiotics drug resistance Antibacterial drugs drug resistance medications, which attempt to slow bacterial growth or kill bacterial cells. This resistance is called antibiotic resistance. Antibiotic resistance Bacterial infections Antibiotic resistance Treatment Antibiotic resistance Treatment antibiotic resistance

Development History

The first antibiotics, penicillin Beta-lactam antibiotics bacterial resistance to and the aminoglycoside streptomycin, were identified in the 1940s, and bacteria adapted quickly to block the drugs’ effects. Resistance to beta-lactam antibiotics was noted in 1944 and accounted for more than three-quarters of hospital Nosocomial infections antibiotics acquired infections in 1950. The long-term risk of resistance was acknowledged as early as 1956.

Excitement about the treatment potential of these early antibiotics, which were introduced in the 1940s and 1950s, contributed to the drugs’ rapid, widespread use. Antibiotic use became more promoted and more commonplace in the 1950s and 1960s and was often prescribed empirically and inappropriately, without regard to long-term resistance effects such as increased virulence Virulence and multiple resistance mechanisms.

By the 1960s, methicillin-resistant Staphylococcus aureus Methicillin-resistant Staphylococcus aureus (MRSA) was identified, and MRSA rates continued to increase in the United States into the twenty-first century from just greater than 2 percent in 1975 to nearly 60 percent in 2003. As reported by the Centers for Disease Control and Prevention (CDC) in 2013, however, the MRSA rates in the United States fell between 2005 and 2011 by 31 percent. As MRSA spread through hospital populations and even into animal and community groups, the last-resort glycopeptide antibiotic vancomycin was used more frequently. In September, 2007, vancomycin-resistant Vancomycin-resistant Staphylococcus aureus and vancomycin-intermediate S. aureus were identified in the United States. Bacteria have developed physical methods and genetic mutations to prevent, reduce, or inactivate antibiotic activity against them.

Mechanisms of Resistance

Microbes have eight identified major mechanisms of drug resistance that are typically based on an attack of the drug structure, drug-bacteria interaction, or drug quantity around the bacterial cell. More than one mechanism can be used at a time to develop widespread resistance, and different mechanisms are more effective for different antibiotic classes. Once the bacteria develop resistance to an antibiotic, the benefit is passed on to others in the same drug class through genetic mutations in the infectious deoxyribonucleic acid (DNA). Thus, the mutations and resistance spread among people as the bacterial disease is spread. This concept of antibiotic-resistant bacteria in people who have not been directly exposed to the antibiotic supports the urgency of counteracting resistance throughout the human population.

Bacterial resistance develops because of changes to enzymes, target sites, or cell-wall components. Examples of enzyme-mediated resistance are the development of beta-lactamase, which targets beta-lactam antibiotics for inactivation, and the development of a new enzyme that is not affected by antibiotics. Reduced bacterial cell-wall permeability, particularly with gram-negative bacteria, is also a common resistance method; drug efflux Drug efflux, which occurs when bacteria pump antibiotics from the bacterial cell, is most common with tetracycline antibiotics. Changes to the target site on the bacteria, in which antibiotics cannot recognize the binding site and attack bacteria, are less common with beta-lactams and more common with quinolones and macrolides. In some cases, bacteria may otherwise block the target site to prevent antibiotic binding; this occurs against tetracycline antibiotics in particular. Bacteria may increase the amount of binding sites on the wall too, so that antibiotics cannot achieve sufficient proportional concentrations for activity, especially with sulfonamide treatment and with glycopeptides such as vancomycin.

Cellular adaptations that help bacteria avoid any interaction with antibiotics and binding of antibiotics elsewhere on the bacteria to prevent action on the bacterial cell target also incur drug resistance; the latter method is specific to glycopeptides like vancomycin.

Methods to Reduce Resistance

Early attempts to decrease resistance started in the 1980s, when hospitals began instituting guidelines to cycle, or rotate, antibiotic use for certain diseases. Cyclic administration of antibiotics consists of restricting the prescribing of the most commonly used antibiotic and favoring an alternative antibiotic treatment instead.

Research in the late twentieth and early twenty-first centuries has identified no real evidence of success at minimizing resistance with cycling, and many factors about resistance and efficacy are still unknown. However, restricted antibiotic use in the Netherlands and in Scandinavia resulted in decreased hospital occurrences of MRSA, which supports closely monitored antibiotic prescribing as a means to reduce resistance buildup.

A clear correlation between occurrence of resistance and empiric use of antibiotics, reported in the May, 2010, issue of the British Medical Journal, has supported the longstanding belief that nonempiric treatment (treatment that is identified on the basis of factual data that shows efficacy, such as a sensitivity analysis) will reduce the likelihood of increasing antibiotic resistance because of ineffective antibiotic use. Although occurrence reductions have not been proven, the rate of resistance development is likely to be lower when antibiotics are used properly.

The prohibition of the use of human antibiotics Antibiotics livestock in animals is debated among health experts. The use of antibiotics in animal husbandry to prevent infections in livestock, such as cattle, pigs, and chickens, can increase the rate of resistant bacteria development by introducing primary antibiotics before they even infect humans. Although animal use of antibiotics began in the 1950s to improve the health and quantity of livestock for food use, the practice is now banned in the European Union and in countries around the world. However, the United States has not banned antibiotic use in animals; the US Food and Drug Administration (USDA), though, has emphasized the importance of reducing antibiotics in meat consumed by humans to reduce drug resistance for treatment of human infections. According to the USDA, however, over 32 million pounds of antibiotics sold in the United States in 2012 were used for food animals, which was a 16 percent increase since 2009. The Food and Drug Administration (FDA) released two policy documents in 2013 that addressed the use of antibiotics in food animal production. Despite criticisms, many are optimistic that the issue is being addressed.

Impact

Drastic changes to bacteria can occur in a relatively short time (often within one decade) to reduce antibiotic efficacy, and much needs to be done in identifying the means to long-term resistance. To preserve the effectiveness of antibiotics, doctors must prescribe them with more care and attention. Sensitivity analyses, which identify the antibiotics that retain activity against specific microbes in a particular patient, are increasingly used in hospital settings to determine initial antibiotic therapy and to monitor continued antibiotic use and infection response.

Beginning in 1996, antimicrobial stewardship identified the connection of bacterial resistance with widespread antibiotic use even in persons who had not received the particular resistance-antibiotic treatment. Fewer antibiotics are being developed in the twenty-first century, in part because of the high cost of development. These high costs, fewer successful treatment options, and increased resistance mutations (including multidrug or multimechanism patterns) have increased the urgency to improve antibiotic use and to find nontraditional methods to suppress bacterial infections.

Further Reading

1 

Arias, Cesar A., and Barbara E. Murray. “Antibiotic-Resistant Bugs in the Twenty-first Century: A Clinical Super-Challenge.” New England Journal of Medicine 360.5 (2009): 439–43. Print.

2 

“FDA Annual Summary Report on Antimicrobials Sold or Distributed in 2012 for Use in Food-Producing Animals.” FDA. US Department of Health and Human Services, 2 Oct. 2014. Web. 30 Nov. 2015.

3 

Forsbeg, Kevin J., et al. “The Shared Antibiotic Resistome of Soil Bacteria and Human Pathogens.” Science 337.6098 (2012): 1107–11. Print.

4 

“New FDA Policies on Antibiotic Use in Food Animal Production.” PEW Trusts. Pew Charitable Trusts, 10 Mar. 2015. Web. 30 Nov. 2015.

5 

Polk, Ronald E., and Neil O. Fishman. “Antimicrobial Stewardship.” Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Eds. Gerald L. Mandell, John F. Bennett, and Raphael Dolin. New York: Churchill Livingstone/Elsevier, 2010. Print.

6 

“Public Gets Early Snapshot of MRSA and C. difficile Infections in Individual Hospitals.” CDC. US Department of Health and Human Services, 12 Dec. 2013. Web. 30 Nov. 3015.

7 

Rosenblatt-Farrell, Noah. “The Landscape of Antibiotic Resistance” Environmental Health Perspectives 117.6 (2009): 244–50. Print.

8 

Schmitz, Franz-Josef, and Ad C. Fluit. “Mechanisms of Antibacterial Resistance.” Cohen and Powderly Infectious Diseases. 3rd ed. Eds Jonathan Cohen, Steven M. Opal, and William G. Powderly. Philadelphia: Mosby/Elsevier, 2010. Print.

9 

Taube, Gary. “The Bacteria Fight Back.” Science 321.5887 (2008): 356–61. Print.

10 

Walsh, Christopher. Antibiotics: Actions, Origins, Resistance. Washington: ASM, 2003. Print.

Web Sites of Interest

Centers for Disease Control and Prevention

http://www.cdc.gov/drugresistance

National Institute of Allergy and Infectious Diseases

http://www.niaid.nih.gov/topics/antimicrobialresistance

Todar’s Online Textbook of Bacteriology

http://www.textbookofbacteriology.net

World Health Organization

http://www.who.int/drugresistance

See also: Alliance for the Prudent Use of Antibiotics; Antibiotics: Experimental; Antibiotics: Types; Bacterial infections; Chemical germicides; Drug resistance; Glycopeptide antibiotics; Hospitals and infectious disease; Iatrogenic infections; Ketolide antibiotics; Macrolide antibiotics; Methicillin-resistant staph infection; Microbiology; Public health; Quinolone antibiotics; Reinfection; Secondary infection; Superbacteria; Treatment of bacterial infections; Vancomycin-resistant enterococci infection.

Citation Types

Type
Format
MLA 9th
Van Hoey, Nicole M. "Antibiotic Resistance." Salem Health: Infectious Diseases & Conditions, 2nd Edition, edited by H. Bradford Hawley, Salem Press, 2020. Salem Online, online.salempress.com/articleDetails.do?articleName=Infect2e_0033.
APA 7th
Van Hoey, N. M. (2020). Antibiotic resistance. In H. B. Hawley (Ed.), Salem Health: Infectious Diseases & Conditions, 2nd Edition. Salem Press. online.salempress.com.
CMOS 17th
Van Hoey, Nicole M. "Antibiotic Resistance." Edited by H. Bradford Hawley. Salem Health: Infectious Diseases & Conditions, 2nd Edition. Hackensack: Salem Press, 2020. Accessed September 16, 2025. online.salempress.com.