Antimicrobial resistance
Antimicrobial resistance occurs when the antimicrobial agent (antibiotics, anti-viral, antifungal, antiprotozoal) which was used to treat the diseases caused by a microorganism (bacteria, fungi, virus, protozoa) become ineffective in killing or reducing the growth of the microorganism. The microorganism develops new mechanisms that will protect them from the effect of the drug/ antimicrobials. This post provides an overview of antimicrobial resistance- its causes, mechanisms, complications, prevention and much more.
It is important to understand that our body does not become resistant to the drug but the infection causing microorganism becomes resistant to the antimicrobial agent (AMA). Due to resistance there is increased use of last-line therapy antibiotics. AMR results in reduced treatment options.
Resistance can be of two types- natural and acquired.
Causes of antimicrobial resistance
Microorganisms naturally become resistant to medications over the course of time but certain factors can speed up the process. They are
- Inappropriate use of antimicrobial agents (misuse or overuse)
- Using antimicrobials for self-limiting infections.
- Using antibiotics to treat viral infections (cold)
- Prolonged use of antimicrobial agents for infection prophylaxis.
- Using broad spectrum antibiotics when narrow spectrum antibiotics can treat the infection.
- Increase in severely ill hospitalized patients
- Frequent invasive device use
- Frequent invasive procedures
- Poor infection control
Mechanism of antimicrobial resistance
AMR can occur due to the following mechanisms
1. Mutation
A random, spontaneous and heritable genetic change replaces a sensitive strain by a resistant strain. Resistance due to mutation can be a single step or multistep process.
Eg. Enterococci resistance to streptomycin
2. Gene transfer
The gene responsible for resistance is transferred from one microbe to another by conjugation (penicillin resistance of gonococci), transduction (Staphylococcus aureus) or transformation (Pneumococcal resistance to penicillin G).
3. Drug tolerance
Tolerance towards a drug occurs either by loss of affinity to the target site in the microorganism to an antimicrobial agent or by acquisition of an alternative metabolic pathway by the microorganism.
Eg. Penicillin resistant pneumococcal strains.
4. Drug destroying
The resistant microorganism develops an enzyme which inactivates the drug.
Eg. Gonococci produces 𝛃-lactamase which inactivates penicillin-G.
5. Drug impermeability
The antimicrobial agent is not able to enter the microorganism due to the changes made by the organism in their cell wall or due to the efflux pumps which remove or push the drug from the cell.
Eg. Chloroquine resistant P.falciparum.
6. Cross resistance
This commonly occurs in between mechanically or chemically related drugs. Resistance develops towards drugs from the same class or drugs from another class.
Eg. Resistance to a sulfonamide means resistance to other sulfonamides.However, resistance to any one aminoglycoside may not extend to another aminoglycoside- gentamicin resistant MO may still respond to amikacin.Partial cross resistance can sometimes be seen in unrelated drugs like tetracyclines and chloramphenicol.
7. Multiple resistance mechanisms
Some organisms develop resistance due to a combination of various mechanisms.
Who is at risk of antimicrobial resistance?
AMR can affect anyone but the following are more vulnerable.
- Babies especially premature babies
- Old aged people (>65 years)
- People living in crowded areas
- People with compromised immunity
- Long term antimicrobial usage
What are superbugs?
Superbugs are microorganisms that do not respond to the first line antimicrobials used for the treatment of diseases caused by them. Infections caused by superbugs are tedious to treat.
Examples of superbugs
- MRSA- Methicillin resistant staphylococcus aureus.
- VRE- Vancomycin resistant Enterococci
- MRD-TB: Multiple drug resistant Mycobacterium tuberculosis
- Carbapenem resistant Enterobacteriaceae
- Candida auris
- HIV
- Malaria (Plasmodium falciparum)
- Klesbsiella pneumoniae
- Escherichia coli H30-Rx
- Multidrug resistant Acinetobacter
- Extended spectrum beta lactamase (ESBL) producing Enterobacteriaceae
- Multidrug resistant Pseudomonas aeruginosa
Complications of antimicrobial resistance
AMR causes an increase in
- Morbidity
- Mortality
- Length of hospital stay
- Medical costs
AMR also leads to
- Decreased treatment options.
- Treatment with new and costly antimicrobials which can be costly and have more adverse effects.
Measuring antibiotic sensitivity
Microorganism cultures (in vitro) are grown in the presence of antimicrobial agents. The commonly used tests to test resistance or sensitivity are
- Kirby- Bauer test/ Disk diffusion test
- E-test
- Newer tests which examine the mutations in the genes of microorganisms linked to resistance are also being done (HIV).
The culture tests used to isolate the microorganisms and identify the sensitive antimicrobial agents is time consuming. Speeding up the antimicrobial susceptibility tests will help in rapid identification and treatment of the infection.
Prevention of antimicrobial resistance
Antimicrobial resistance is a global health issue and containing it requires implementation of multiple level strategies (local, national and international). This ensures the rational use of antimicrobial agents. Understanding the causes, complications, risk factors, implications and prevention of antimicrobial resistance is of great importance.
The following can be followed to prevent antimicrobial resistance
- Using selective narrow spectrum antibiotics instead of broad spectrum.
- Limiting antimicrobial use and using it only when necessary.
- Isolating people with resistant microbe infections in hospitals.
- Using combination therapy in case of long term use of antimicrobials (eg. TB, HIV)
- Preventing infection by
- Maintaining personal hygiene
- Washing hands with soap and water (for at least 20 seconds).
- Avoiding contact with infected people.
- Wearing masks when necessary
- Getting vaccinated
- Taking medications to prevent infection (in some cases)
- Preventing food borne infections (food hygiene)
- Taking medications the correct way (correct-dose, frequency, duration etc.)
- Resistant microbes must be treated intensively
- Monitoring local resistance patterns in hospitals and the community in order to ensure effective antimicrobial therapy.
- Public awareness measures that help to educate people about antimicrobial resistance- its causes, complications, prevention, risk factors and much more.
- Completing the antimicrobial course.
- Restricting treatment with newer agents when the infection can be treated with older agents.
- Local and international stewardship programmes must be conducted to monitor antimicrobial use.
- Effective infection control in hospitals to decrease the dissemination of resistant microorganisms.
Written by Auxi Arobana. R