Antimicrobial Therapies Flashcards
What’s an antibiotic
An anti microbial agent produced by a microorganism that kills other microorganisms
Soil dwelling fungi are most commonly used
Bactericidal meaning
Kills bacteria
Bacteriostatic meanjng
Stops bacterial growth
Antiseptic meanjng
Chemical that kills or inhibits microbes used topically on skin
Beta lactams
Penicillin,methicillin
Bind to PBPs interfere with cell wall synthesis
Sulphonamides
Prontosil,trimethoprim,sulfa methoxazole
Bacteriostatic can cause host toxicity
Prontosil treats UTI,RTI
Becoming more common due to AB resistance
Aminoglycosides
Gentamycin, steptomycin
Target 30s ribosomes subunits ,damage Cell membrane,rna proofreading
Rifampicin
Bactericidal targets RpoB subunit of rna polymerase
Causes red secretions
Vancomycin
Bactericidal targets lipid component of cell wall and wall cross linking via d ala residues
Toxic
Linezolid
Bacteriostatic inhibits initiation of protein synthesis by binding to 50s rRNA
Gram positive bacteria
Daptomycin
Targets bacterial cell membrane
Gram positive bacteria
Bactericidal
Macrolides
Target 50s ribsomal subunits preventing amino acyl transfer and thus truncation of polypeptides
Gram positive and negative
Quinolones
Synthetic broad spectrum Bactericidal targets dna gyrase in gram negative and topoisomerase in gram positive
As the antibiotics Bactericidal
All are apart from linezoid and sulphonamide
What is the minimal inhibitory conc
The lowest concentration of antibiotic needed to inhibit growth
When is a bacterium considered resistant
If it can grow at or above the minimal inhibitory concentration
4 mechanisms through which antibiotic resistance occurs
Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation
Altered target site
MRSA encodes alternative PBP with low affinity for beta lactams
Acquisition of erm gene by streptococcus pneumoniae encodes enzyme that methylates AB target site in 50s ribosmal subunit leading to resistance
Inactivation of antibiotic
Enzymatic degradation or alteration
Rendering antibiotic ineffective
- e.g. beta-lactamase (bla) and chloraphenicol acetyl-transferase (cat)
For example ESBL AND NDM-1 are. Betalactamases
Altered metabolism
Increased production of enzyme substrate can out-compete antibiotic for target site,
(e.g. increased production of PABA confers resistance to sulfonamides).
Or bacteria can switch to other metabolic pathways, reducing requirement for PABA
Decreased drug accumulation
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 3 sources of antibiotic resistant genes
- Plasmids- extra-chromosomal circular DNA often carry multiple copies and often carry multiple AB resistant genes so selection for one maintains resistance for 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
How can bacteria spread their ab resistant genes
1) Transformation- uptake of extracellular DNA
2) Transduction- phage-mediated DNA transfer
3) Conjugation- bacterial sex to share plasmids between them (pilus-mediated DNA transfer)
Non genetic mechanisms of resistance
Bio is so slow & persistent BISSP
- Biofilm
- Intracellular location
- Slow growth
- Spores
- Persisters
What other reasons are there for ab treatment failure
- Inappropriate choice for organism e.g. some ABs kill gram positive but not negative
- Poor penetration of AB into target site
- Inappropriate dosage (half life)
- Inappropriate administration (oral vs IV)
- Presence of AB resistance within commensal flora e.g. secretion of beta-lactamase
Hospital acquired infections nosocomal
- High number of ill people
- Crowded wards
- Presence of pathogens
- Broken skin e.g. surgical wound or IV catheter
- Indwelling devices e.g. intubation where bacteria can come together and form biofilm
- AB therapy may suppress normal gut microbiota that helps maintain gut health
- Transmission by staff- contact with multiple patients
- How might AB therapy impair commensal flora (microbiota)?AB therapy removes commensal organisms that helps maintain gut health and health of whole bodyPathogen has no competition leading to overgrowthPathogen produces toxins and damages host-symptomatic infectionSpreads to other patients!https://s3-us-west-2.amazonaws.com/secure.notion-static.com/0886ed10-86db-4f93-bcf5-408afb500cf2/Untitled.png
- Give some of the methods we might use to address antibiotic resistance(6 ways; BE SICK)?
- Reduce use of broad-spectrum antibiotics (that can destroy gut microbiota)
- Modification of existing medication to e.g. prevent cleavage (beta lactams) or enhance efficacy e.g. methicillin
- Strategies of prescription- tighter controls, temporary withdrawal of certain classes to allow prevalence of resistant organisms to drop before reintroduction- restriction of ABs for certain serious infections
- Identify infections caused by resistant strains quickly
- Combination therapy- using 2 or more AB together + inhibitors
- Knowledge of local strains/resistance patterns
- Fungi- what are the 3 classes of conditions they cause in humans?
- 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
- What do fungi use in their cell membrane instead of cholesterol?Ergosterol
- What are the targets for antifungal therapy?!https://s3-us-west-2.amazonaws.com/secure.notion-static.com/b8a01b08-180d-4b75-929d-5797712dc929/Untitled.png
How might ab therapy impair commensal flora
AB therapy removes commensal organisms that helps maintain gut health and health of whole body
Pathogen has no competition leading to overgrowth
Pathogen produces toxins and damages host-symptomatic infection
Spreads to other patients
Fungi
Cause allergy, mycotoxicoses and mycoses
Gram negative
pseudomonas aeruginosa
Cystic fibrosis,burn wound infections,survives in a biotic surfaces
e.coli
GI infect,neonatal meningitis,septicemia,uti
salmonella
Thyphoid,GI infection
acinetobacter baumannii
Wounds,uti,pneumonia
neisseria gonorrhoeae
Gonorrhaea
Gram positive
staphylococcus aureus
Wound and skin infection,pneumonia,septicaemia,endocarditis
streptoccus pneumoniae
Pneumonia,septicemia
clostridium difficile
Diarrhea,colitis
mycobacterium tuberculosis
Tuberculosis
What replaces cholesterol in fungi cell wall
Ergosterol
