The word “antibiotic” refers to the compounds that are “against life”. Technically, any drug that can kill infectious agents (like bacteria and fungi) are antibiotics. More specifically, antibiotics are anti-microbial substances or antibacterial or antifungal agents which are used for fighting infections. Based on the mode of action, they may be bacteriostatic which inhibits bacterial growth or bactericidal which kills the bacteria. Antibiotic resistance happens when the infectious bacteria or fungi are no longer susceptible to the action of antibiotics. Infections caused by such antibiotic-resistant bacteria and fungi are difficult to treat as the antibiotic can no longer kill them or prevent them from replicating. This is the reason why antibiotic-resistant infections need extended stays in the hospital, additional follow-up with the doctor and the use of toxic and costly alternatives to combat the infection. The phenomenon of antibiotic resistance can affect people of literally any age group and occupation which makes it one of the most important topics of global concern. Medical advances like cancer therapy, organ transplantation, organ replacement, treatment of several chronic infections, all depend on the ability of antibiotics to fight infections. In such cases, the prevalence of antibiotic resistance could be highly problematic.

History

Penicillin was the first antibiotic to be commercialized in the year 1941 while penicillin-resistant Staphylococcus aureus and Streptococcus pneumonia were identified in the years 1942 and 1967 respectively. Azithromycin was first identified in the year 1980 while azithromycin resistant Neisseria gonorrhoeae was identified in 2011. Amphotericin B was identified in 1959 while the first amphotericin resistant Candida auris was identified in 2016. Similarly, resistant strains have been identified for nearly all the identified antibiotics. This global crisis of antibiotic resistance has been attributed to the excessive overuse and misuse of antibiotics and lack of development of novel drugs.

Benefits of antibiotics

  1. They played a key role in the advancements in medicine and surgery.
  2. They have prevented and cured several bacterial and fungal infections in patients with diabetes, arthritis, cancer, organ transplant, heart surgery, etc.
  3. They changed the outcome of bacterial infections and improved the life span of the several affected individuals.
  4. They decreased food-borne and poverty-induced morbidity and mortality in developing nations.

Causes of antibiotic resistance

  1. Lack of awareness among the medical professionals and the general public.
  2. Poor personal hygiene practices and water sanitation results in infection.
  3. Lack of rapid and reliable tests to determine antibiotic resistance.
  4. Lack of vaccines for key infections.
  5. Lack of antibiotics that can combat multidrug-resistant bacteria.
  6. Lack of a coordinated and global response to antibiotic usage.
  7. Absence of antibiotic resistance surveillance programs to track the resistant cases in a geographical location.
  8. Improper disposal of expired or unused medicines may expose the microbes to several antibiotics and trigger resistance.
  9. Use of antibiotics in livestock animals.
  10. Mutation, selection pressure or gene transfer in the bacteria.

Mechanisms of antibiotic resistance

Antibiotic resistance mechanism

Bacteria have evolved with multiple strategies to exhibit antibiotic resistance. They may either block the antibiotic from reaching the target or may modify or bypass the specific targets to attenuate the effect of antibiotics. For blocking the antibiotic from reaching the target, the bacteria may follow at least four different mechanisms. This includes pumping out the incoming antibiotic, decreasing the membrane permeability to limit the intracellular entry of the antibiotic, enzymatic cleavage of the antibiotic to make it ineffective or enzymatic modification of the antibiotic. Bacteria employ at least three different mechanisms to modify or bypass the target of the antibiotic. This includes camouflaging the target by bringing about a change in the composition or the structure, production of alternative proteins which can be used instead of the ones inhibited by the antibiotic or by reprogramming the target through the production of structural variants of the target.

Consequences of antibiotic resistance

  1. Increased use of antibiotics due to resistance development.
  2. Failure in treating chronic problems like diabetes, cancer, arthritis, etc.
  3. Alternative treatments are less effective, more costly and toxic.
  4. Increased chances of relapse after the treatment.
  5. Increased healthcare cost and longer hospital stays.
  6. Lack of the availability of effective antibiotics.

Antibiotic-resistant bacterial infections

Some of the antibiotic-resistant bacterial infections which pose a big threat across the globe include

  1. Methicillin-resistant Staphylococcus aureus
  2. Vancomycin-resistant Enterococci
  3. Drug-resistant Streptococcus pneumoniae
  4. Drug-resistant Mycobacterium tuberculosis
  5. Carbapenem-resistant Enterobacteriaceae
  6. Multidrug-resistant Pseudomonas aeruginosa
  7. Multidrug-resistant Acinetobacter
  8. Extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae

Prevention of antibiotic resistance

  1. Don’t use antibiotics for viral infections as they are ineffective against viruses.
  2. Always complete the antibiotic treatment procedure. Do not miss the dose or terminate it as soon as you get better.
  3. Don’t self-prescribe antibiotics. Always consult a medical professional.
  4. New antibiotics should be developed
  5. Effective diagnostic tests should be devised to identify the drug-resistant bacteria.
  6. Livestock should not be given antibiotics effective in humans.
  7. Getting vaccinated against the diseases rather than using antibiotics.
  8. Stay safe in the hospital so that you do not succumb to nosocomial infections.
  9. Pharmaceutical effluents and industrial wastewater should be treated properly before release.

Non-antibiotic therapies for antibiotic-resistant pathogens

Scientists are working on non-antibiotic therapies to cut down the use of antibiotics. Such therapies include the use of

  1. Viruses, more precisely bacteriophage which can consume the bacteria.
  2. Monoclonal antibodies to nullify the effect of microbial toxins
  3. Vaccines to prevent the recurrence of infection.
  4. Faecal microbiota transplant
  5. Probiotics, postbiotics and synbiotics
  6. Nanoantibiotics

References

  1. https://www.cdc.gov/drugresistance/about.html
  2. https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance
  3. C Lee Ventola MS, 2015. The antibiotic resistance crisis. Pharmacy and Therapeutics. 40(4): 277-283
  4. https://www.webmd.com/cold-and-flu/antibiotic-resistance
  5. https://www.rxlist.com/antibiotic_resistance/drugs-condition.htm
  6. https://www.medicinenet.com/antibiotic_resistance/article.htm
  7. https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/antibiotic-resistant-bacteria
  8. https://www.fda.gov/consumers/consumer-updates/combating-antibiotic-resistance
  9. https://www.medicalnewstoday.com/articles/283963#prevention
  10. https://amr.biomerieux.com/en/about-amr/how-do-bacteria-become-resistant-to-antibiotics/
  11. Kumar M, Sarma DK, et al., 2021. Futuristic non-antibiotic therapies to combat antibiotic resistance: A review. Frontiers in Microbiology. https://doi.org/10.3389/fmicb.2021.609459.

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