Antibiotic Resistance

What is Antibiotic Resistance?

Antibiotic resistance is a critical and growing public health issue that occurs when bacteria and other microbes evolve to resist the effects of antibiotics, making infections harder to treat. This phenomenon arises primarily due to the overuse and misuse of antibiotics in healthcare, agriculture, and even the environment. For example, prescribing antibiotics for viral infections, failing to complete prescribed doses, or using antibiotics as growth enhancers in livestock accelerates the development of resistant bacteria. Over time, resistant strains such as MRSA (methicillin-resistant Staphylococcus aureus) or multi-drug resistant tuberculosis (MDR-TB) spread which limit treatment options and increase mortality rates.

More than 2.8 million antimicrobial-resistant infections occur annually in the U.S.

Impact on the General Population

When antibiotics lose their effectiveness, infections that were once treatable can become life-threatening. Surgeries, chemotherapy, and other medical procedures that rely on antibiotics to prevent infections become riskier. The World Health Organization (WHO) has identified antibiotic resistance as one of the top 10 global public health threats because it undermines modern medicine's ability to save lives.

Without effective antibiotics, common infections such as urinary tract infections (UTIs), pneumonia, and bloodstream infections become increasingly dangerous. Additionally, hospital-acquired infections become harder to manage, especially in ICUs or post-surgical care settings. The global death toll due to antibiotic-resistant infections could rise dramatically, with estimates predicting up to 10 million deaths annually by 2050 if urgent action isn't taken.

Figure 1. How antibiotic resistance works.

1. Efflux Pumps

   • Some bacteria use tiny "pumps" to push antibiotics out of their cells, stopping the medication from working.

2. Breaking Down Antibiotics

   • Bacteria can produce special enzymes that break apart antibiotics, making them useless.

3. Changing the Target

   • Antibiotics work by attacking specific parts of bacteria, but bacteria can change these parts, so the antibiotic no longer fits or works.

4. Blocking Antibiotics from Entering

   • Bacteria can make their cell walls or membranes harder to get through, so antibiotics can’t even enter to do their job.

5. Modifying Proteins or Cell Walls

   • They can also tweak their structures, like proteins or cell walls, to block the effects of antibiotics.

6. Sharing Resistance Genes

   • Bacteria have "instruction manuals" in their DNA (like plasmids) that they can share with other bacteria, teaching them how to resist antibiotics too.

How Does Antibiotic Resistance Develop?

Antibiotic resistance occurs when bacteria evolve mechanisms to withstand the effects of the drugs designed to kill them or stop their growth. This means that the antibiotic no longer works effectively against the bacteria. Antibiotic resistance is a natural process but it is significantly accelerated by the misuse and overuse of antibiotics.

How does this happen?

1. Bacteria can mutate, which means they can undergo small changes in their DNA. These mutations can occur naturally as a part of bacterial reproduction. A bacterium can survive in the presence of an antibiotic if a mutation confers a survival benefit, such as being able to neutralize or escape the antibiotic.

2. Even without direct mutation, bacteria can acquire antibiotic resistance through horizontal gene transfer. This occurs when bacteria exchange genetic material with each other. There are three main ways this can happen:

   • Conjugation: Bacteria can physically connect through a pilus (a hair-like structure found on the surface of many bacteria which helps them stick to cells or surfaces) and transfer plasmids (small DNA molecules) that carry antibiotic resistance genes.

   • Transformation: Some bacteria can take up fragments of DNA from their surroundings, including resistance genes.

   • Transduction: Viruses that infect bacteria (called bacteriophages) can carry antibiotic resistance genes from one bacterium to another.

3. When antibiotics are used, they create what’s called selective pressure on bacterial populations. This means that the bacteria that have resistance mechanisms will survive and continue to reproduce, while the non-resistant bacteria are killed off. Over time, the resistant bacteria become more dominant in the population.

Types of Antibiotic Resistance Mechanisms

Figure 1. How antibiotic resistance works.

1. Some bacteria produce enzymes that break down or inactivate antibiotics. For example, beta-lactamase is an enzyme that breaks down the beta-lactam ring structure found in penicillin and related antibiotics, rendering them ineffective.

2. Some bacteria have efflux pumps. Efflux pumps are proteins in bacteria cell membranes that actively pump antibiotics out of the cell before the drug can exert its effect. This helps the bacteria avoid the toxic effects of the antibiotic.

3. Bacteria can modify or mutate the molecular target sites where antibiotics usually bind. For example, the antibiotic methicillin targets a specific protein (penicillin-binding protein) involved in bacterial cell wall synthesis. If the bacteria change this target protein, methicillin can no longer bind effectively which makes it useless.

4. Some bacteria alter their outer membranes or cell walls to prevent antibiotics from entering the cell. This can involve the closing off channels or porins that normally allow antibiotics to pass through the bacterial cell wall.

5. Many bacteria can form biofilms. Biofilms are dense, protective layers of bacteria embedded in a sticky matrix of extracellular substances. Biofilms make it harder for antibiotics to penetrate and effectively kill the bacteria. Biofilm-associated infections are common in medical devices like catheters or implants, where bacteria are shielded from the immune system and antibiotics.

Consequences of Antibiotic Resistance

As bacteria become resistant to multiple antibiotics, the available treatments for infections become limited. This causes multidrug-resistant bacteria. In some extreme cases, we have "superbugs," which are bacteria that are resistant to most or all available antibiotics. For example, Methicillin-resistant Staphylococcus aureus (MRSA) and Carbapenem-resistant Enterobacteriaceae (CRE) are two examples of superbugs. Antibiotic resistance can lead to longer hospital stays, more intensive treatments, and an increased risk of complications or death from otherwise treatable infections. It also increases the overall cost of healthcare because more expensive or less effective drugs may be needed to treat resistant infections

Disproportionate Impact on Socioeconomically Disadvantaged Communities

While antibiotic resistance affects the entire population, its impact is magnified among socioeconomically disadvantaged groups due to several systemic and structural barriers. People in low-income communities often lack access to timely and appropriate healthcare. Limited resources mean that many turn to substandard or counterfeit antibiotics that are less effective and contribute to resistance. Additionally, many do not complete treatment courses due to cost constraints which leads to partial elimination of bacteria and subsequent resistance.

• Overcrowding and Poor Sanitation
  Socioeconomically disadvantaged areas frequently face overcrowded living conditions and poor sanitation, creating an environment where resistant bacteria spread easily.

  • Poor access to clean water exacerbates diseases like cholera or diarrheal illnesses, often requiring antibiotics for treatment.

  • Lack of proper waste management allows antibiotics from human, animal, and agricultural sources to contaminate the environment, further driving resistance.

• Lack of Awareness and Education
  In underserved populations, there is often limited public health education about the proper use of antibiotics. Without clear understanding:

  • Antibiotics may be overused (e.g., using them unnecessarily for colds or flu).

  • Misuse, such as sharing antibiotics or stopping treatment early, becomes common.

• Economic Burden
  Antibiotic-resistant infections require longer hospital stays, more expensive treatments, and prolonged recovery periods. For individuals with low incomes:

  • These added healthcare costs can be catastrophic.

  • Lost wages and inability to work due to prolonged illness worsen economic hardships.

• Global Disparities in Healthcare Infrastructure
  In developing nations, healthcare systems often lack resources like proper diagnostics to identify antibiotic-resistant infections. As a result:

  • Broad-spectrum antibiotics are overprescribed as a precaution, contributing to resistance.

  • Patients suffer higher mortality rates due to delays in receiving appropriate treatment.

Broader Societal Implications

Antibiotic resistance exacerbates existing health inequities by disproportionately impacting vulnerable groups:

• Children, the elderly, and immunocompromised individuals are particularly at risk as they rely heavily on antibiotics to fight infections.

Preventing antibiotic resistance requires action at multiple levels, from individuals to healthcare systems and policymakers. On an individual level, people must use antibiotics responsibly by taking them only when prescribed by a healthcare provider, avoiding sharing antibiotics or using leftover medications, and always completing the full course of treatment. Good hygiene practices, such as regular handwashing, safe food handling, and staying up to date on vaccinations, can reduce the risk of infections that require antibiotics. Public education is also essential to help people understand the difference between bacterial and viral infections and the dangers of antibiotic misuse.

Sources

1. “Antibiotic Resistance Outline Diagram, Illustrated Mechanism in Bacteria Cell Stock Vector - Illustration of Mechanism, Health: 231919386.” Dreamstime, www.dreamstime.com/mechanisms-antibiotic-resistance-outline-diagram-illustrated-example-alternation-drug-target-activation-drug-efflux-pumps-image231919386.

2. “Antimicrobial Resistance - Hope.” Hope, 2018, hope.be/hope_working_area/antimicrobial-resistance/. Accessed 16 Dec. 2024.

3. Cleveland Clinic. “Antibiotic Resistance: What Is It, Complications & Treatment.” Cleveland Clinic, 19 Oct. 2023, my.clevelandclinic.org/health/articles/21655-antibiotic-resistance.

4. World Health Organization. “Antimicrobial Resistance.” World Health Organization, World Health Organization, 21 Nov. 2023, www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance.

5. U.S. Food and Drug Administration (FDA). Antimicrobial Resistance. U.S. Food and Drug Administration, 2023, https://www.fda.gov/animal-veterinary/safety-health/antimicrobial-resistance.

6. Centers for Disease Control and Prevention (CDC). Antibiotic Resistance. Centers for Disease Control and Prevention, 2023, https://www.cdc.gov/drugresistance/index.html.

7. National Institutes of Health (NIH). Antibiotic Resistance. National Institutes of Health, 2023, https://www.nih.gov/news-events/nih-research-matters/antibiotic-resistance.