IA. General Microbiology | 13. Possible mechanisms of resistance against antibiotics

Question 1

I. Types of resistance against antibiotics
1. What are the 5 types of resistance against antibiotics?

Answer 1

1. Resistance in clinics
2. Natural resistance
3. Acquired resistance
4. Cross resistance
5. Poly-resistance

Question 2

I. Types of resistance against antibiotics
2. What is Resistance in clinics?

Answer 2

a quantitative measure where the MIC is higher than the maximal dose tolerated by the host

Question 3

I. Types of resistance against antibiotics
3A. What are the features of Natural resistance?

Answer 3

Natural resistance: characteristic of the species
- Against the antibiotic produced by themselves
- Cell wall barrier (Gram negative), or lack of cell wall (Mycoplasma)
- Lack of transport system
- Lack of receptors
- E.g. enterobacteriaceae, pseudomonas aeruginosa and members of the Haemophilus genus is resistant to penicillin G
- Streptococcus pyogenes is resistant to gentamicin

Question 4

I. Types of resistance against antibiotics
3B. Give an example of natural resistance

Answer 4

Enterobacteriaceae, pseudomonas aeruginosa and members of the Haemophilus genus is resistant to penicillin G

Question 5

I. Types of resistance against antibiotics
3C. What is Streptococcus pyogene to?

Answer 5

gentamicin

Question 6

I. Types of resistance against antibiotics
4A. What is Acquired resistance?

Answer 6

• The development of resistance by an organisms (which was sensitive before) due to prolonged use of an antimicrobial agent
• 2 types: Vertical and Horizontal

Question 7

I. Types of resistance against antibiotics
4B. What are the 2 types of acquired resistance? Pls give definitions as well

Answer 7

1. Vertical: spontaneous mutations (evolution, selection)
2. Horizontal(*most common): giving resistance genes to each other
   - Conjugation
   - Transduction
   - Transformation

Question 8

I. Types of resistance against antibiotics
4C. What are the 3 mechanisms of acquired resistance? Pls give definitions as well

Answer 8

• Conjugation: main mechanism for spread of resistance; the conjugative plasmids make connecting tube between the 2 bacteria through which the plasmid can pass
• Transduction: acquisition of bacterial DNA from a phage that has incorporated DNA from a previous resistant host
• Transformation: free DNA is picked up from the environment (i.e. from cell belonging to closely related or same strain)

Question 9

I. Types of resistance against antibiotics
5A. What is Cross resistance?

Answer 9

Cross resistance: the bacteria are resistant to several antibiotics belonging into the same antibiotic class
- E.g. MRSA is resistant to all B-lactams

Question 10

I. Types of resistance against antibiotics
5B. Give an example of Cross resistance?

Answer 10

E.g. MRSA is resistant to all B-lactams

Question 11

I. Types of resistance against antibiotics
6A. What is Poly-resistance?

Answer 11

Poly-resistance: the bacteria are resistant to several different antibiotic classes
- E.g. the nosocomial pathogens (P.aeruginosa, Acinetobacter baumanii)
- Methicillin resistant staphylococci are often resistant to macrolides, fluoroquinolones, tetracyclines, and chloramphenicol

Question 12

I. Types of resistance against antibiotics
6B. Give examples of poly-resistance

Answer 12

Poly-resistance: the bacteria are resistant to several different antibiotic classes
- E.g. the nosocomial pathogens (P.aeruginosa, Acinetobacter baumanii)
- Methicillin resistant staphylococci are often resistant to macrolides, fluoroquinolones, tetracyclines, and chloramphenicol

Question 13

II. Resistance mechanisms
1. What are the 5 Resistance mechanisms?

Answer 13

1. Production of enzymes that inactivate the drug
2. Altered permeability to the drug results in decreased effective intracellular concentration
3. Synthesis of altered structural targets for the drug
4. Multi-drug resistance pump (efflux pump)
5. Altered metabolic pathway
   - that bypasses the reaction inhibited by the drug

Question 14

II. Resistance mechanisms
2. One of resistance mechanisms is the Production of enzymes that inactivate the drug
=> Give an example

Answer 14

E.g Penicillinase enzyme cleaves portion of molecule making it inactive

Question 15

II. Resistance mechanisms
2. One of resistance mechanisms is Altered permeability
=> Explain

Answer 15

Altered permeability to the drug results in decreased effective intracellular concentration
- Receptor that transports drug is altered so drug cannot enter the cell

Question 16

II. Resistance mechanisms
3. One of resistance mechanisms is Multi-drug resistance pump
=> Explain

Answer 16

Multi-drug resistance pump (efflux pump)
- Specialized membrane proteins activated and continually pump drug out

Question 17

II. Resistance mechanisms
4. One of resistance mechanisms is Altered metabolic pathway
=> Explain

Answer 17

Altered metabolic pathway that bypasses the reaction inhibited by the drug
- Usually pathway blocked by drug so microbe uses alternate pathway to achieve outcome

Question 18

III. Most important antibiotic resistant organisms
1. What are the 5 most important antibiotic resistant organisms?

Answer 18

1. MRSA, MRSE
2. ESBL Producing bacteria
3. Metallo B-lactamase production
4. Fluoroquinolone resistance
5. Vancomycin resistance

Question 19

III. Most important antibiotic resistant organisms
2. What are the features of MRSA, MRSE?

Answer 19

Methicillin resistant Staphylococcus aureus; S. epidermidis
- Resistant because of the changes in the PBP (penicillin binding proteins)
- Coded by the mecA gene on the chromosomal cassette, can be exchanged in the genus
- Resistant to all B-lactams!!! (and normally many other antibiotic groups)
- Glycopeptides can be administered against them BUT resistance against them have already appeared (VISA, VRSA)

Question 20

III. Most important antibiotic resistant organisms
3. What are the features of ESBL Producing bacteria?

Answer 20

• Extended spectrum B-lactamase mainly produced by Gram negative bacteria like E.coli and Klebsiella
• Resistant to penicillins, cephalosporins
• Only carbapenems can be used from the B-lactams, so ability to produce carbapenemase is appeared and spreading amongst the bacteria

Question 21

III. Most important antibiotic resistant organisms
4. What are the features of Metallo B-lactamase production?

Answer 21

Resistant to penicillins, cephalosporins, carbapenems

Question 22

III. Most important antibiotic resistant organisms
5. Give an example of Fluoroquinolone resistance?

Answer 22

E.g. Klebsiella sp

Question 23

III. Most important antibiotic resistant organisms
6. Give an example of Vancomycin resistance?

Answer 23

Enterococcus sp

Question 24

IV. What are the 7 factors affecting antibiotic resistance?

Answer 24

1. Patient forgets to take their medication
2. Patient interrupts their treatment when they begin to feel better
3. Irrational use of antibiotics in human practice
4. Unnecessary, inadequate dose
5. Over prescribing of broad spectrum drugs when narrow spectrum are appropriate
6. Wrong prescription guidelines
7. Irrational use of antibiotics in animals