antimicrobial therapies Flashcards
- Define antibiotic
- What are most antibiotics used today produced by?
Antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms.
Target many different bacterial processes and are SELECTIVELY TOXIC Soil-dwelling fungi (eg penicillin) or bacteria (streptomyces)
- Define antimicrobial
- Define bactericidal
- Define bacteriostatic
- Define antiseptic
Chemical that selectively kills or inhibits microbes
Kills bacteria Stops bacteria growing Chemical that kills or inhibits microbes, that is used to prevent infection
- What was the first example of sulphonamide antibiotic?
- What is prontosil used to treat?
Prontosil
Urinary tract infections Respiratory tract infections Bacteraemia Prophylaxis for HIV + individuals
- What are the reasons for why antibiotic resistance may lead to increased mortality, morbidity 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 2 examples of aminoglycosides
- What processes do aminoglycosides target?
Gentamicin, Streptomycin
Protein synthesis
RNA proofreading
- What ribosomal subunit do aminoglycosides target?
- Are aminoglycosides bactericidal or bacteriostatic?
- What has lead to an increasing use of aminoglycosides?
30S
Bactericidal
Resistance to other antibiotics
- What is the mechanism of rifampicin?
- What colour does rifampicin make your secretion go?
Targets RpoB subunit of RNA polymerase (bactericidal)
Spontaneous resistance is frequent
Orange/red (affects patient compliance)
- What is the mechanism of vancomycin and is it bactericidal or bacteriostatic?
- What has lead to increasing use of vancomycin?
Targets Lipid II component of cell wall biosynthesis, as well as wall cross-linking via D-ala residues
Bactericidal
Resistance to other antibiotics e.g. against MRSA
- What spectrum of activity does linezolid have?
- What is the mechanism of linezolid?
Gram-positive spectrum of activity
Inhibits the initiation of protein synthesis by binding to 50S rRNA subunit (bacteriostatic)
- What limits the dose of daptomycin?
- What is the mechanism of daptomycin?
- What is the spectrum activity of daptomycin?
Toxicity
Bactericidal - targets bacterial cell membrane Gram-positive spectrum
- Give 2 examples of beta-lactams
- What is the mechanism of beta-lactams?
Penicillin, Methicillin
Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall (bind to penicillin-binding proteins) Bactericidal
- Give 2 processes that are unique to bacterial cells
Production of peptidoglycan
Maintenance of LPS layer of gram negative bacteria
- Give 2 examples of macrolides
- What types of infections can macrolides be used against?
- Describe the mechanism of macrolides
Erythromycin, Azithromycin
Gram-positive, Some gram-negative infections Targets 50S ribosomal subunit preventing amino-acyl transfer Thus truncation of polypeptides
- What do quinolones target in gram negative bacteria?
- What do quinolones target in gram positive bacteria?
DNA gyrase
Topoisomerase IV
- What is meant by resistance?
- Why might there be more of a resistance to penicillin in hospitals than the community?
If a bacterium can grow at or above the breakpoint concentration (minimal inhibitory concentration of antibiotic)
Routine use of penicillin in hospitals provides a selection pressure For the acquisition and maintenance of resistance genes
- What are the 4 distinct mechanisms by which antibiotic resistance can occur?
Altered target site
Inactivation of antibiotic Altered mechanism Decreased drug accumulation
- Give 2 examples in which a target site can be altered
MRSA encodes alternative PBP with low affinity for beta lactams
Acquisition of erm gene by streptococcus pneumoniae encodes an enzyme that methylates AB target site in 50S ribosomal subunit
- How does inactivation of antibiotics occur?
- What is one of the greatest threats to antibiotic use at the moment?
Enzymatic degradation or alteration
Rendering antibiotic ineffective
Bacteria that encode broad spectrum of beta lactamase enzymes Such as ESBL and NDM-1 which can degrade a wide range of beta-lactam
- How does the altered metabolism pathway occur within antibiotic resistance?
- How does decreased drug accumulation occur?
Increased production of enzyme substrate can out-compete antibiotic for target site
Or bacteria can switch to other metabolic pathways, reducing requirement for PABA (if sulphonamide is drug used)
Reduced penetration of AB into bacterial cell Or increased efflux pumps to keep AB out of cell Makes it so that drug does not reach concentration required to be effective
- What are the 3 sources of antibiotic resistant genes and how do they work?
Plasmids - extrachromosomal circular DNA, often carry multiple AB resistant genes so selection for one maintains resistance for all
Transposons - integrate into chromosomal DNA and allow transfer of genes from plasmid to chromosome and vice versa Naked DNA - DNA from dead bacteria released to environment
- Describe the 3 ways that bacteria can spread their AB resistant genes
Transformation - uptake of extracellular DNA
Phages - viruses infect bacteria and take up some of their DNA and then go on to infect other bacteria, passing on the DNA
Conjugation- bacterial sex to share plasmids between them
- Give some of the non-genetic mechanisms of resistance/treatment failure
Biofilm - matrix encased communities of bacteria that are highly drug tolerant will minimise penetrative effect of antibiotics
Intracellular location - harder for antibiotics to get to bacteria Slow growth -hard for bacteria to inhibit replication processes if they do not occur as much Persisters - dormant bacteria that are not carrying out the processes that antibiotics inhibit Spores - resistant to heat, antiseptics and also antibiotics, spore coat is impermeable to antibiotics, preventing access to the target organelles
- What are 3 solutions to reducing antibiotic resistance?
- In what sectors are antibiotics used more?
Phage antibiotic combination therapy
Modifications of existing antibiotics (prevent cleavage)
Combination of inhibitor and antibiotic
Critical care Wards
- What are some of the risk factors for HAI?
High number of ill people
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
- How might AB therapy impair commensal flora?
AB therapy removes commensal organisms
Pathogen has no competition leading to overgrowth Pathogen produces toxins and damages host-symptomatic infection Spreads to other patients
- Give some of the methods we might use to address resistance
Prescribing strategies - tighter controls, temporary withdrawal of certain classes and restrictions of ABs for certain serious infections
Reduce use of broad spectrum antibiotics Quicker identification of infections caused by resistant strains Combination therapies Clinicians should have knowledge of local strains and resistance patterns
- What 3 broad classes of conditions are caused by fungi?
- What do fungi use in their cell membrane instead of cholesterol?
Allergy - allergic reactions to fungal products
Mycotoxicoses - ingestion of fungi or their toxic products
Mycoses - superficial, subcutaneous or systemic colonisation, invasion and destruction of human tissue
Ergosterol
What are the three targets for antifungal therapy
Cell membrane- made from ergosterol rather than cholesterol
DNA synthesis- some molecules only activated by fungi. arresting DNA synthesis
Cell wall- fungi have cell wall unlike mammalian cells
