Hospital acquired infection and antibiotic resistance Flashcards
Reasons for high rate of hospital-acquired infection
- High numbers of ill people
- Very crowded wards
- High amounts of pathogen nearby
- Broken skin from surgical wounds, IVs, catheters
- Antibiotic therapy allows antibiotic-resistant pathogens to accumulate
- Transmission by staff who don’t wash hands properly
Antimicrobial definition
A chemical that selectively kills or inhibits microbes
Bactericidal definition
Kills bacteria
Bacteriostatic definition
Stops bacteria growing
Antiseptic definition
A chemical that kills or inhibits microbes, usually used topical to prevent infection
Minimal inhibitory concentration definition
The lowest concentration of antibiotic required to inhibit growth
Tetracycline mechanism of action
- Targets protein synthesis
- Binds to 30s ribosomal subunit
- Prevents peptide elongation
Chloramphenicol mechanism of action
- Targets protein synthesis
- Binds to 50s ribosomal subunit
- Prevents peptidyl transfer step
Erythromycin mechanism of action
- Targets protein synthesis
- Gram positive bacteria affected
- Truncation of polypeptides
Sulphonamides mechanism of action
- Inhibition of essential metabolites
- Targets specific enzymes
List of important bacteriostatic antimicrobials
- Tetracycline
- Chloramphenicol
- Erythromycin
- Sulphonamides
List of important bactericidal antimicrobials
- Beta-lactams (penicillin, methicillin)
- Quinolones
- Gentamicin
- Streptomycin
Penicillin/methicillin (beta-lactams) mechanism of action
- Targets cell wall synthesis
- Bind to Penicillin Binding Protein (PBP) and inhibit function
- No peptidoglycan synthesised
Quinolones mechanism of action
- Inhibit nucleic acid replication and transcription
- Target DNA gyrase in Gram negative
- Target topoisomerase in Gram positive
Gentamicin/Streptomycin mechanism of action
- Target protein synthesis
- Targets 30s ribosomal subunit
Reason for antimicrobials acting as selective pressure on microbes
Antimicrobial usage will kill all bacteria who do not possess resistance genes in a population. However, those that do will survive, and thus proliferate further until the new population is entirely resistant to that antimicrobial. Thus here the antimicrobial has acted as a selection pressure.
Genetic mechanisms of resistance
- Altering target site for antimicrobials, e.g. encoding an alternative PBP
- Inactivation of antibiotic, e.g. enzyme degradation of antibiotic molecules, encode beta-lactamase which breaks down beta-lactams
- Antibiotic efflux, e.g. encoding for efflux pumps which pump antibiotic molecules back out of cell
- Altered metabolism, e.g. increasing production of substrate to out-compete antibiotic as inhibitor, can switch to other uninhibited metabolic pathways
- Decreased drug accumulation, e.g. reduced penetration of antibiotic into bacteria
Non-genetic mechanisms of antibiotic resistance
- Forming a biofilm
- Changing intracellular location of targeted sites
- Slow growth
- Spores
- Persisters
Penicillin resistance mechanisms
- Penicillinases break down antibiotic, gained from plasmid transformation
- Modification of PBP, gained from point mutation
Tetracycline resistance mechanism
Efflux pump, gained by plasmid conjugation
Quinolone resistance mechanism
Target site modification, gained by point mutation
Cefotaxime resistance mechanisms
Target site modification, gained by point mutation
Sources of antibiotic resistance genes
- Plasmids
- Transposons, integrate into chromosomal DNA, allows transfer of genes from plasmid to chromosome and vice versa
- Naked DNA from dead bacteria in environment
Mechanisms of antibiotic resistance gene spread
- Transformation, uptake of extracellular DNA
- Transduction, phage inserts resistance gene into cell
- Conjugation, DNA transferred from cell to cell by a conjugation bridge
