Antibiotic resistance Flashcards
What are 3 uses of antibiotics and its result?
- Prophylactic: pre-surgery, immunocompromised, oncology
- Empirical therapy: signs of infection seen, don’t know causative agent
- Therapeutic: know causative organism, more testing and monitoring
- More infections, treatment failures, costs, toxicity, increased risk of procedures or hospital stay
- Affects all branches of medicine
Describe how antibiotics can be inhibited by drug inactivation or altered targets by bacteria, giving examples
Drug Inactivation: acquired β-lactamase destroys the β-lactam ring in penicillins and cephalosporins
Altered/New Target: acquired mecA gene by MRSA codes for penicillin binding protein 2a. PBP2a target site doesn’t bind methicillin or other β-lactam antibiotics, so isn’t inhibited
Other: ribosomes, porins, DNA gyrase (R+ to quinolones), RNA polymerase (R+ to rifampicin), Mcr1 and colistin can all be altered!
How can altered transport and mass target production inhibit antibiotics?
Efflux Pumps: remove antibiotics quickly. Pumps can either be acquired, or can acquire mutations that allow them to work faster
Antibiotics that competitively inhibit a target can be overcome by mass production of the target-> not enough drug to inhibit the target.
What is metabolic bypass? Use this to explain vancomycin resistance
Metabolic by-pass: bacteria by-pass the part that the antibiotic inhibits
e.g. Vancomycin binding to the terminal D-ala, D-ala unit inhibits peptidoglycan synthesis.
Bacteria can develop a metabolic by-pass by replacing the last D-ala residue w D-lac (lactate) = vancomycin cannot recognise and bind = R+ vancomycin
How can penicillin prevent normal bacterial cell wall synthesis?
Penicillin bind to and block the function of PBPs
Preventing normal cell wall synthesis and stability
(Peptidoglycan strong due to cross links and synthesis catalysed by PBPs/transpeptidases)
Describe the 4 mechanisms that prevent penicillin action and make bacteria resistant?
Produce penicillinase/ beta-lactamase secreted through cell wall out into environment
Porin mutates so is now unable to transfer the penicillin across into bacterial cells
PBP mutates/ bacteria acquires new PBP so cant bind penicillin
Efflux pumps pump out penicillin more efficiently
3 ways bacteria take up foreign DNA?
Transformation: DNA is taken up by bacteria from environment
Transduction: phage viruses infect an cause lysis of bacteria , release phage particles that bind and inject their DNA into recipient bacteria
Conjugation: 2 bacteria close contact form pilli/pore transfers DNA between them
List 3 ways Gram negative bacteria may be penicillin resistant
- natural [intrinsic] resistance
- genetic mechanisms
- non-genetic mechanisms [growth phases]
What are the two types of genetic mechanisms for antibiotic resistance
- chromosome-mediated
- spontaneous mutation in target molecule or in the drug uptake system
- mutations are selected, not induced
- horizontal gene transfer
- transformaiton, transduction, conjugation
- multidrug resistance possible following plasmid transfer via conjugation
What are the non-genetic mechanisms of antibiotic resistance?
Inaccessibility to drugs, e.g. abscess or TB lesion: the vascular blood supply is poor resulting in lack of antibiotic delivery to infection site
Stationary phase bacteria/biofilms: not affected by antibiotics which inhibit cell wall synthesis bc they’re not doing anything
What is Co-amoxiclav?
Co-amoxiclav/Augmentin= amoxicillin (a β-lactam antibiotic) and Clavulanic acid (has β-lactam structure but has no antibiotic properties)
Clavulanic acid inactivates b-lactamases – this protects amoxicillin from beta-lactamase-> amox still works
How can disc diffusion be used to test for antibiotic resistance?
if the red circle is present, that means that the bacteria is senstitive to the bacteria (no bacterial growth)
if the bacteria is resistant, then the red circle does not appear because you have bacterial growth
Outline the different ways that antibiotic resistance can be overcome/prevented
Describe the history of methicillin resistant Staphylococcus aureus (MRSA)
How does resistance to beta-lactams differ in Gram +ve and Gram -ve bacteria?
neg = alteration in porins
pos = alteration in PBPs
penicillinase destroys active part of penicillin by hydrolysis (CN)
