Microbiology 3 Hospital acquired infection and antibiotic resistance Flashcards
List the reasons for the high rate of infections in hospitals
- Large numbers of infected people receive high doses of antibiotics (strong selective pressure)
- Crowded wards
- Broken skin - surgical wound/IV catheter
- Indwelling devices - intubation (eg. catheters)
- AB therapy may suppress normal flora
- Transmission by staff - contact with multiple patients
What are the mechanisms of action of antibiotics?
- Inhibition of cell wall synthesis
- Inhibition of protein synthesis
- Inhibition of nucleic acid replication and transcription
- Injury to plasma membrane -Inhibition of synthesis of essential metabolites
What is prontosil and how does it work?
- First sulphonamide antibiotic
- Bacteriostatic (stops bacterial growth)
What are beta-lactams and how do they work?
- Antibiotics such as penicillin and methicillin
- Inhibit peptidoglycan synthesis (bind to penicillin-binding proteins)
What are aminoglycosides and how do they work?
- They are bactericidal (kill bacteria)
- Eg. streptomycin
- Target protein synthesis/RNA proofreading and cause damage to the cell membrane
- Limited use as they are toxic
What is rifamicin and how does it work?
- Bactericidal (kills bacteria)
- Targets RpoB subunit of RNA polymerase.
- Spontaneous resistance is frequent.
- Makes secretions go orange/red - affects compliance.
What is vacomycin and how does it work?
- Bactericidal.
- Targets Lipid II component of cell wall biosynthesis, as well as wall crosslinking via D-ala residues
- Toxicity has limited use, but resistance to other antibiotics has led to increasing use e.g. against MRSA
What is linezolid and how does it work?
- Bacteriostatic.
- Inhibits the initiation of protein synthesis by binding to the 50S rRNA subunit.
- Gram-positive spectrum of activity.
What is datomycin and how does it work?
- Bactericidal.
- Targets bacterial cell membrane.
- Gram-positive spectrum of activity.
- Toxicity limits dose.
What are quinolones and how do they work?
- Synthetic, broad spectrum, bactericidal.
- Target DNA gyrase in Gm-ve and topoisomerase IV in Gm+ve.
What are macrolides and how do they work?
- E.g. Erythromycin, azithromycin.
- Gram-positive and some Gram-negative infections.
- Targets 50S ribosomal subunit preventing amino-acyl transfer and thus truncation of polypeptides.
Summarise the mechanisms for antibiotic resistance.
- Altered target site (acquisition of alternative gene or a gene that encodes a target modifying gene)
- Inactivation of the antibiotic (enzyme degradation or alteration)
- Altered metabolism (alternative pathways/increased production of the substrate)
- Decreased drug accumulation (reduced penetration or increased efflux - drug cant reach concentration required to be effective)
What are the sources of antibiotic resistant genes?
- Plasmids - extra-chromosomal circular DNA, often multiple copy. Often carry mutliple AB res genes - selection for one maintains resistance to all.
- Transposons. Integrate into chromosomal DNA. Allow transfer of genes from plasmid to chromosome and vice versa.
- Naked DNA. DNA from dead bacteria released into environment.
List important bacterial pathogens that are multi-drug resistant.
- Pseudomonas aeruginosa
- Cystic fibrosis
- E. Coli (ESBL)
- EKlebsiella spp (NDM-1)
- Salmonella spp. (MDR)
- Acinetobacter baumannii (MDRAB)
- Neisseria gonorrhoeae (Gonorrhoea)
- Staphylococcus aureus
- Streptococcus pneumoniae
- Clostridium difficle
- Enterococcus spp
- Mycobacterium tuberculosis
Why is antimicrobial resistance associated with increased mortality¬ morbidity and cost?
- Increased deaths as fewer patients can be treated
- Increased morbidity as the disease will be present longer so can spread
- Increased cost as antibiotics used are toxic so result in side effects and longer treatments
