ANTIBIOTICS RESISTANCE Flashcards
- What is an antibiotic, and what distinguishes it from general compounds with antimicrobial activity?
Antibiotic actually and literally means against life. They are compounds with antimicrobial activity. But not all antimicrobials are antibiotics. Antimicrobials are compounds which work on a big variety of organisms, such as fungi, yeast, viruses. But antibiotics only stops bacterial growth.
- Why are antibiotics so important for modern medicine?
Antibiotics revolutionized modern medicine and are pretty much the only way to fight bacterial infections. But apart from fighting bacterial infections, they are also used for:
- Enabling safe open surgeries. During these procedures there is a huge risk of infection.
- Support cancer therapy, specially for patients who are immunodepressed. Prophylaxis
- Support transplant patients. Prophylaxis
- For veterinary medicine
- What are the main causes that lead to the current antimicrobial resistance crisis?
- The overuse of antibiotics. Sometimes we do not need them. They are commonly mis prescribed for treating viral infections. This is due to the lack of real-time efficient diagnostics, especially for respiratory infections.
- Sometimes patients do not finish their treatment.
- Overuse in livestock and fish farming.
- Poor infection controls in clinics. Tropical countries have more problems with this. It is more difficult to deal with humidity.
- Lack of hygiene and poor sanitation.
- Lack of interest of pharmaceutical industries in investing in antibiotics development
- Enumerate 3 biological processes targeted by antibiotics.
- DNA synthesis and processing. Integrity or replication, polymerase, gyrase. Fluoroquinolones.
- Cell wall biosynthesis. Beta-lactams. They are very appreciated antibiotics. These are the ones that have the least secondary effects, but be careful with secondary infections.
- Protein biosynthesis: ribosomes. They cannot survive without proteins. Aminoglycosides.
- Define antibiotic resistance and describe one method that can be used to measure it.
Antibiotic resistance is the ability of microbes to grow in the presence of “high” concentrations of a given antibiotic.
How are we actually measuring susceptibility to drugs in bacteria? By measuting how it is affecting growth and how it is killing the bacteria.
1. Growth inhibition: it measures growth. It measures the minimum inhibitory concentration (MIC).
We are focusing on measuring growth.
Measuring antibiotic susceptibility: Growth:
The goal is to determine which is the minimum concentration of an antibiotic in order to inhibit the growth of the bacteria. Antibiotic resistance is solely dependent on inhibiting the ability to grow. There are very good antibiotics that do not kill bacteria, but still prevent the growth well enough. The immune system will do the rest. Resistances is based on growth, not on killing. We have to possibilities to measure this:
- In agar petri dishes. It is called calibrated dichotomous sensitivity (CDS). You create a bacterial lawn. You then put disks with antibiotics at a certain concentration. Then it diffuses. The bacteria which are sensitive will not grow. They are as sensitive as the hallo. You can measure the hallo to determine the MCI. Instead of the disks, you can use stripes. The concept is really similar. You can read the concentration in the stripe, and see the MIC.
- In liquid culture-microtiter plates. This is a little bit more precise. You don’t have to use a rule hehe. You can measure many samples is the same plate, and also culture different bacteria. This is called Broth microdilution. You do serial dilutions of you compound and see which concentration is sufficient to inhibit the growth of bacteria. The concentration before it inhibits the growth is actually the MCI. This method is more flexible and more quantitative.
- What determines resistance to a given antibiotic: its ability to kill bacteria or to inhibit bacterial growth?
What actually determines resistance to a given antibiotic is the ability to inhibit bacterial growth. Observing that we have more bacterial killed after the treatment with that antibiotic does not actually give any information about the level of resistance the bacteria have acquired.
- Why are Gram-negative bacteria generally more intrinsically resistant to antibiotics?
Gram- bacteria typically have higher intrinsic resistance to antibiotics (remember the Pseudomonas thing). All bacteria have inner membrane. Most of them have a cell wall. It is a hard layer which gives them their shape. But the Gram- they have additionally another membrane. It is called the outer membrane composed of lipopolysaccharides. It is a lipid layer negatively charged which gives the bacteria an extra permeability layer. To cross the membrane the antibiotic have to cross that charge membrane. Then through the wall and then through an apolar membrane again. It is very difficult to find such a compound.
- What are the 3 most common antibiotic resistance mechanisms?
- Target mutations: typical example is what happens with fluoroquinilones. When you target the gyrase, there is a selective pressure for a while. Then it will develop DNA gyrase mutations in the chromosome. It can be acquired and de novo.
- Antibiotic modification: Beta lactamases. These are enzymes that degrade beta lactams. The bacteria acquire a gene that degrade the antibiotic before it can interact with the target. It is acquired and also can be plasmid base. It is easily transferable. Some of them are secreted to the outside as well. It is a very efficient method. You can avoid this the best. B-lactams are administered with b-lactamase inhibitors.
- Drug efflux: bacteria have pumps. They are extremely unspecific. It can be intrinsic and acquired.
- Define antibiotic persistence. How does it differ from resistance?
Antibiotic persistence is the ability of a bacteria to survive antibiotic treatments without developing antibiotic resistance. In a resistance situation the bacteria actually developed mechanisms to evade antibiotic action. Persistance is:
- mostly physiological as they very very slow growing bacteria. - genetic determinants are as wellbeing suggested. - increasingly shown to within host.
- Enumerate 3 bacterial species listed on the WHO’s high-priority list for antibiotic development.
Staphylococcus Aureus (MRSA)
Clostidrium difficile
Mycobacteirum tuberculosis
