Hospital acquired infection and antibiotic resistance Flashcards
What is the breakpoint?
- The concentration of antibiotic that can be achieved in a clinical setting
- If the bacteria can divide at a concentration at or higher than the breakpoint = resistant
What is resistance?
The ability of an organism to replicate in the presence of an antibiotic at a particular concentration
What is minimal inhibitory concentration (MIC)?
The lowest concentration of the antibiotic required to inhibit growth
Name some gram+ major antibiotic resistant bacterial pathogens and the disease they cause
- Staphylococcus auerus (MRSA) = penumonia, septicaemia, infective endocarditis
- Streptococcus pneumoniae = pneumonia, septicaemia
- Clostridium difficile = antibiotic-associated diarrhoea, pseudomembranous colitis
Name some gram- major antibiotic resistant bacterial pathogens
- E. coli = Gi infection, neonatal meningitis, septicaemia, UTI
- Salmonella spp. = GI infectino, thyphoid fever
- Neisseria gonorrhoeae = gonorrhoea
Why does antimicrobial resistance lead to increased morbidity, mortality and cost?
- Increased time to effective therapy
- Requirement for additional approaches (e.g. surgery)
- Use of expensive therapy (newer drugs)
- Use of more toxic drugs (e.g. vancomycin)
- Use of less effective ‘second choice’ antibiotics
Give a reason for the high rate of hospital acquired infection
Strong selective pressures in hospitals due to the regular use of antibiotics
Name some examples of hospital acquired infections
- Methicillin-resistant S. aureus (MRSA)
- Vancomycin-insensitive S. aureus (VISA)
- Clostridium difficile
- E. coli
What are the risk factors for hospital acquired infections?
- High number of ill people (immunosuppression)
- Crowded wards
- Presence of pathogens
- Broken skin - surgical wound/IV catheter
- Indwelling devices - intubation
- AB therapy may suppress normal flora
- Transmission by staff - contact with multiple patients
What is selective toxicity in the context of antimicrobial drugs?
They will kill microbial cells but not host’s cells
What are the four main mechanisms of antibiotic resistance?
- Altered target site
- Inactivation of antibiotic
- Altered metabolism
- Decreased drug accumulation
Summarise the mechanism of inactivation of antibiotic
- Acquire gene for an enzyme that breaks down the antibiotic
- E.g. β-lactamase and chloramphenicol acetyl-transferase
Summarise the mechanism of altered target site
- Can arise from acquisition of an alternative gene or a gene that encodes a target-modifying enzyme.
- Acquire a gene which performs the same function but has different structure = not susceptible to the AB
- E.g. MRSA encodes an alternative penicillin binding protein (PBP) with low affinity for β-lactams
- E.g. Streptococcus pneumoniae reistance to erythromycoin = acquisition of the ‘erm’ gene = encodes an enzyme that methylates the AB target site = change structure
Summarise the mechanism of altered metabolism
- Re-engineer the metabolic pathways = bypass the step that antibiotic interferes with
- Increased production of enzyme substrate = outcompetes antibiotic inhibitor
Summarise the mechanism of decreased drug accumulation
Reduce penetration of antibody into bacterial cell (permeability) and/or increase efflux of antibodies out of the cell = drug does not reach concentration required to be effective
