Antimicrobial therapies Flashcards
Define antibiotic
Antimicrobial agent produced by microorganisms that kills or inhibits other microorganisms
Define antimicrobial
Chemical that selectively kills or inhibits microbes
Define bactericidal and bacteriostatic
Kills bacteria
Stops bacteria growth - stops replication
Define antiseptic
Chemical that kills/inhibits microbes
Why don’t antibiotics harm human cells?
ABs have selective toxicity. They target different bacterial processes not found in mammals.
Which different bacterial processes do ABs target?
DNA replication Cell wall synthesis Plasma membrane damage Protein synthesis - Transcription - Translation Enzymatic activity/synthesis of metabolites
What is prontosil and what does it act on?
Why is it being used more now?
First sulphonamide - bacteriostatic and synthetic
Used for UTIs, RTIs, bacteraemia, prophylaxis for HIV patients
only works on gram positive bacteria
used more due to resistance to other ABs however has some host toxicity
Why are sulphonamides sometimes used with trimethoprim?
Sulphonamides target biosynthetic pathways such as folate synthesis
trimethoprim targets folate synthesis too
Used in conjunction they have synergic effects leading to more effective treatment
Give examples of beta-lactams and explain how they function
Penicillin or methicillin
Typically bactericidal - interfere with the synthesis of the peptidoglycan component of the bacterial cel wall
Binds to penicillin-binding proteins responsible for manufacturing the cell wall
Give examples of amioglycosides and explain how they function
Bactericidal or bacteriostatic?
Why are they dangerous to use?
Gentamicin
Streptomycin
Bactericidal - target protein synthesis by targeting 30s ribosomes, RNA proofreading and cause cell damage to membrane
Host toxicity - can cause hearing loss - used more due to AB resistance
Give examples of amioglycosides and explain how they function
Gentamicin
Streptomycin
Bactericidal
Targets protein synthesis, RNA proofreading and cause damage to cell membrane
Are toxic and can cause hearing loss
Give some examples of sulphonamides, what are they used in conjunction with?
Prontosil
Sufla-methoxazole
Used with Trimethoprim
What does Rifampicin do? Bactericidal or bacteriostatic?
What side effect does it have?
Bactericidal- targets RpoB unit of RNA polymerase which blocks transcription and has good activity on bacteria inside host cells ie neutrophils
spontaneous resistance is common, also causes red/Orange secretions so compliance is an issue
What does Vancomycin do? Bactericidal or bacteriostatic?
What side effect does it have?
Bactericidal - Targets lipid II component of cell wall biosynthesis as well as crosslinking via D-ala residues
Very toxic - must be given intravenously - used more for things like MRSA
What does Linezolid do? Bactericidal or bacteriostatic?
What type of bacteria does it act on?
Bacteriostatic - inhibits initiation of protein synthesis by binding to the 50s ribosomal RNA subunit
Only effective on gram positive bacteria
What does daptomycin do? Bactericidal or bacteriostatic?
What type of bacteria does it act on? Why is dosage limited?
Bactericidal
Targets bacterial cell membrane
active on gram positive bacteria - relatively toxic so limited dose
Give some examples of macrolides. What does they do? Bactericidal or bacteriostatic?
What type of bacteria does it act on?
Erythromycin, azithromycine
Bacteriostatic
Target 50s ribosomal subunits preventing amino-acyl transfer and thus truncation of polypeptides
Mostly gram positive some gram negative
What doe quinolones do? Bactericidal or bacteriostatic?
What type of bacteria does it act on?
Bactericidal - Synthetic broad spectrum
Targets DNA gyrase in gram negative bacteria and topoisomerase in gram positive bacteria
What is the minimum inhibitory concentration ?
Lowest concentration of AB required to limit growth
What are the four mechanisms for antibiotic resistance?
Altered target site - alternative gene or a gene that encodes a target modifying enzyme
Inactivation - enzymatic degradation or alteration makes the AB ineffective
Metabolism altered - increased production of substrate to out-compete or switch to other metabolic pathways
Drug accumulation - decrease drug accumulation - decreased permeability - increased efflux of AB
What are the three sources of AB resistant genes?
Plasmids - extra-chromosomal circular dna - carry multiple AB resistance genes
Transposons - integrate into chromosomal DNA and allow transfer of genes from plasmid to chromosome and vice versa
Naked DNA - DNA from dead material released into the environment
What are the three mechanisms for horizontal spread of AB resistance in bacteria?
Transformation - uptake of extracellular DNA
Conjugation - attach and out across DNA
Transduction - phage virus that infects bacteria, takes bacteria and passes it to another bacteria
How do you get a high prevalence of AB resistant bacteria in the population?
Population contains cells with AB resistance due to mutations/acquired DNA – possibly with a fitness cost e.g. Slow growth
Presence of selection pressure
In presence of selection pressure (e.g. Abs) resistant mutants outcompete
High prevalence of AB resistant strains in patient population
What are the effects of antibiotic resistance?
Second choice - second choice drug may be less effective
Time to effective therapy is increased
Additional approaches may be needed - eg surgery
Toxic drugs used more ie vancomycin
Expensive therapy - newer drugs may be more expensive
(STATE)
What are the three mechanisms that can alter the target site in bacteria?
Change in target site structure
- Mutation in gene encoding target site > change in peptide sequence > changes structure of target for AB
- a target modifying enzyme gene is acquired
Alternate site - MRSA encodes an alternate penicillin binding protein which has a low affinity for beta lactams
Bacteria can produce enzymes that modify the AB target ie streptococcus pneumoniae via a gene which encodes an enzyme that methylates the AB target site in the 50s ribosomal subunit
What are some non-genetic mechanisms of resistance/treatment failure?
Biofilm Intracellular location Slow growth Spores Persisters
What are 5 reasons for treatment failure aside from Ab resistance?
Inappropriate choice for the organism poor penetration of AB into target site inappropriate dosage inappropriate adminstration Presence of Ab resistance within commensal flora - ie secretion of beta-lactamase
What are the risk factors for HAIs
Crowded wards Antibiotic therapy Broken skin Devices (indwelling) Ill and immunosuppressed patients Pathogens present Staff in contact with multiple patients
What harm can come about when AB therapy affects commensal flora?
Normally commensal flora outcompetes pathogens, if lack of commensal flora, pathogens has less competition and overgrows and produces toxins, damages host and can cause symptomatic infection
What are 6 ways to overcome resistance?
Broad spectrum reduction Existing medication alteration Strategies of prescription Identifying infections quickly Combinations of Abs and inhibitors - ie augmentin Knowledge of local strains/patterns
What Gram negative organism causes hospital acquired pneumonia, burn wounds, particularly affects immunocompromised hosts (e.g. chemotherapy, individuals with cystic fibrosis), and survives on abiotic surfaces?
pseudomonas aeruginosa
