Infections Lecture 3: Bacterial Resistance to Antibiotics Flashcards
How does inherent (natural) resistance to bacteria work?
- Gram negative outer membrane provides a permeability barrier
- It stops sufficient amounts of antibiotic from entering cell to exert its action
How does acquired resistance work?
- A new antibiotic used and most infections then respond
2. Over time treatment fails as resistance is acquired
What are the two ways acquired resistance works?
- Changes in the bacterial genome
- Mutation and Selection: Vertical Evolution
- Exchange of genes between strains and species: horizontal evolution
What is vertical evolution?
- Spontaneous mutation that confers resistance
- Happens in the absence of antibiotics
- Drug does not induce resistance
- Better adapted survive and thrive - All bacterium die and resistant bacterium stays alive to replicate
What is horizontal evolution?
- Bacteria acquire resistant genes from other bacteria
- Swap genes by:
- conjugation: Cell to cell contact, DNA crosses a sex plus
- Transduction: genes transported by bacterial virus
- Transformation: DNA acquired from environment
Give examples of how the conversion of active drug to inert product by an enzyme occurs? (common)
- Gram positive and negative cells can produce beta-lactamase
- Converts Penicillin to penicilloic acid (not antibacterial) - Aminglycosides can be inactivated by acetyl/adenyl/nucloetidyl transferases
- Chloramphenicol (broken by acetylation) (chloramphenicol acetyl transferase)
What is the reduction in cellular permeability to antibiotic?
- Doesn’t allow drug to get to toxic levels in cell
- Change in cell wall and membrane which antagonises antibiotic transport processes (generation of efflux pump)
- Some species pump tetracycline out of cell
Give examples of how changes in the antibiotic target site results in resistance and acquisition resistant form of target enzyme?
- Example: Ribosomes are targeted for erythromycin (modified to prevent binding) (S.aureus)
- Penicillin binding proteins on cell wall which prevented methicillin action also known as MRSA
- Resistance to quinolones due to changed structure of target enzyme DNA gyrase
What are the four mechanisms of actions of bacterial resistance?
- Conversion of active to inert by enzyme
- Reduction in cellular permeability to antibiotic
- Changes to antibiotic target site resulting in resistance
- Altered metabolic pathway
Give an example of how an altered metabolic pathway works?
Trimethoprim resistance when E.coli has its metabolic pathway altered from UTI treatments
How does clostridium difficile emerge?
- Use of antibiotics kill the normal gut flora
2. C. difficile takes over to release toxins
Describe the Glycopoetide Resistant Enterococci and how it obtains its resistance?
- Gram postive cocci
- Enteric: normally found in digestive and urinary that
- Intrinsically resistant to many antibiotics: PBP (penicillin binding protein) bind less well to beta lactams
- Conjugation: acquires the resistance by conjugation (acquired beta lactase)
What does Glycopoetide Resistant Enterococci commonly cause?
Wound infections
Bacteraemia
Abdominal and pelvic infections
Particular problem in immuno-compromised
What is the Carbapenem Resistant Enterobacteriaceae, what are its common names and what are the treatment options?
- Enterobacteriaceae: Gram Negative Bacilli
- Part of gut flora or can be found in soil and water
- Resistant to ost or all available antibiotics
- Most commonly e. coli or salmonella
- Treatment options: Polymyxins, Tigecycline, fosfomycin and aminoglycosides
What is TB?
- Mycobacterium Tuberculosis
2. Contagious infectious lungs
How is TB transmitted and what is the first site of infection?
- Transmitted: aerosol
- First site of infection:
- Lungs
- Primary infection (resolved local scarring)
- Dissemination: miliary infection
What are the common symptoms of TB?
Symptoms:
- Affect every organ in the body
- Lungs: chronic cough, haemoptysis, fever and weight loss
- Brain: meningitis
- Kidney: Local signs of infections, fever, weight loss, hydronephrosis
- L-S spine: bone infections, vertebral collapse and nerve compression
How do you diagnose TB?
- Tissue Biopsy
- Bronchoscopy
- Chest CT scan
- Chest X-ray
- Sputum examination and cultures
How do you do skin testing to indicate TB and how can you prevent TB?
- Darker area of the skin
- Postive skin test is taken to indicate TB exposure and inactive infection
- Prompt treatment important control spread of TB
- BCG vaccination to prevent TB
How do you treat TB?
Multiple antibiotics must be used together for a long period of time to cure TB
XDR-TB treatment
Same as MDR-TB but includes resistance to a quinolone and 1 or more 2nd line injectable
What does MRSA stand for?
Methicillin Resistant Staphylococcus aureaus
What is the nature of resistance of MRSA?
- Gram positive cocci that acquires mecA gene
2. Expression of gene gives penicillin binding protein variant
What are the current antibiotic options for MRSA?
Vancomycin, linezolid and rifampin
How does MRSA occur in patients in hospital environments?
- Patients with open wounds and weakened immune systems
- Staff that do not follow proper sanitary procedures may transfer from patient to patient
- MRSA can survive on surfaces and fabrics
