4.3 Antimicrobial Therapies Flashcards
Why are anti-bacterials safe for humans to use?
Selective toxicity
Target processes in bacteria but not mammals
Describe the mechanism of action of beta-lactams?
They have a beta-lactam ring that binds the serine residue on penicillin binding protein, inactivating it
Thus the cross bridges between peptidoglycan molecules can’t form, so the bacterial cell wall doesn’t form
Thus water enters the bacteria and it dies
What are some examples of beta-lactams?
Penicillin and Methicilin
What is the definition of an antibiotic?
An anti-microbial agent produced by microorganisms that kills or inhibits other microorganisms
What is an anti-microbial?
A chemical that selectively kills or inhibits microbes
What is the difference between bactericidal and bacteriostatic antibacterials?
Bactericidal kills the bacteria
Bacteriostatic stops the bacteria from growing
What is an antiseptic?
Chemical that kills/inhibits microbes, used topically
What is the minimal inhibitory concentration?
The lowest concentration of antibiotic which is required to inhibit growth
What are some effects of antibacterial resistance?
- Longer time needed for therapy to be effective
- Require additional approaches
- Use of expensive therapy (newer drugs)
- Use of more toxic drugs
- Use of less effective “second choice” antibiotics
How does antibiotic resistance emerge?
A population of bacteria will have some bacteria that are resistant and some that are not due to genetic variation
A selection pressure then acts on the population such as the antibiotic - those that are not resistant die, and patient starts to feel better
Patient then stops course of antibiotic but those that can survive still do not die - they live and proliferative meaning the entire population is now resistant
What are the three gram positive bacteria which are resistant to antibiotics?
Streptococcus pneumoniae
Clostriduim difficile
Enterococcus spp
What are three gram negative bacteria which are resistant to antibiotics?
E.coli
Salmonella
Pseudomonas aeruginosa
Which different bacterial processes do antibiotics target?
DNA replication
Cell wall synthesis
Plasma membrane damage
Protein synthesis (translation, transcription)
Enzymatic activity/synthesis of metabolites
Why might you give a patient multiple different antibiotics?
They may act on different stages of bacterial growth and give a symbiotic effect
E.g. sulfonamides and trimethoprim act on two different stages of bacterial development.
What type of antibiotic is prontosil?
Sulphonamide
What is prontosil used to treat?
UTIs and RTIs
Bacteraemia
Prophylaxis for HIV+ individuals
What is the mechanism of protonsil?
Bacteriostatic and synthetic
What bacteria does prontosil act on?
Gram positive bacteria
How does rifampicin work?
Bactericidal antibiotic
Targets the RpoB subunit of RNA polymerase, blocking transcription so the bacteria cannot replicate
What happens to secretions like urine and sweat when a person is on Rifampicin?
Makes them turn orange / red
How does vancomycin work?
Bactericidal, targets lipid II component of cell wall biosynthesis and wall crosslinking via D-ala residues
How does daptomycin work?
Bactericidal, targets cell membrane
What is the problem with daptomycin?
Toxicity limits the dose
How does linezolid work?
Bacteriostatic, binds 50S subunit of rRNA to inhibit protein synthesis
Why is linezolid effective against gram positive mainly?
Due to lipopolysaccharides present in gram positive outer membrane
What are the four main mechanisms of antibiotic resistance? AIMeD
Altered target site
Inactivation of antibiotic
Metabolism is altered
Drug accumulation
Describe with an example of how antibiotics can become resistant through altering the target site
Acquision of an alternative gene that encodes for a target modifying enzyme
E.g. MRSA encodes a different penicillin binding site with a low affinity for the antibiotic
How is Streptococcus pneumoniae resistant to erythromycin?
Acquires the erm gene
Gene encodes for an enzyme that methylates the antibiotic target site in the 50S ribosomal subunit
Give an example of how a bacteria can inactivate an antibiotic
Beta-lactamases and chloramphenicol can degrade beta lactam rings, preventing binding to penicillin binding proteins on bacteria
Give an example of how bacteria can be resistant to an antibiotic through altered metabolism?
Bacteria can produce another enzyme substrate which outcompetes antibiotics
E.g. increased production of PABA confers resistance to sulfonamides
Describe how bacteria can show antibiotic resistance through decreased drug accumulation?
Reduced penetration of antibiotic into the bacterial cell due to increased efflux of antibiotic out of the cell
Thus the drug does not reach the concentration required to be effective
How do bacteria efflux the drug out in order to confer antibiotic resistance?
Efflux pumps
What are two examples of macrolide antibiotics?
Erythromycin and azithromycin
How do macrolides work?
Targets 50s ribosomal subunit preventing amino-acyl transfer thus causing truncation of polypeptides
What types of bacteria do macrolides work on?
Gram positive and some gram negative
How do quinolones work?
Target DNA gyrase in gram negative and topoisomerase IV in gram positive bacteria
What are three sources of antibiotic resistance?
Plasmids, transposons and naked DNA
Describe how plasmids act as a source of antibiotic resistance?
Plasmids are extra-chromosomal circular DNA which often carry extra multiple antibiotic resistant genes - selection for one maintains resistance to all
What are transposons and how can they help to facilitate antibiotic resistance?
Sections of DNA that can move from one location to another in the genome
They can integrate into chromosomal DNA, allowing transfer of plasmid genes to chromosomal DNA and vice versa
What is naked DNA?
DNA that has been released into the surrounding environment from dead bacteria
What are the three mechanisms for horizontal spread of AB resistance in bacteria?
Transformation, conjugation and transduction
What is transformation?
Uptake of extracellular DNA
What is transduction?
Phage mediated DNA transfer
What is conjugation?
Pilus mediated DNA transfer
What are the five non-genetic sources of antibiotic resistance?
Biofilm
Intracellular location
Slow growth
Spores
Persisters
What are the 5 given reasons for treatment failure aside from AB resistance? DOPe AC
Inappropriate Dose (half life)
Inappropriate choice for Organism
Poor Penetration of AB into target site
Inappropriate Administration (oral vs IV)
AB resistance within Commensal flora (e.g. secretion of beta-lactamase)
What has to be taken into consideration when measuring resistance using agar plates and zones of inhibition?
Measureents make in vitro may not fully reflect the situation in vivo
What do hospitals prodivde for antibiotic resistance?
They provide a strong selection pressure
What are the risk factors associated with Hospitals Acquired Infections? CAB DIPS
Crowded wards
Antibiotic therapy
Broken skin
Devices (indwelling)
Ill and immunosuppressed patients
Pathogens
Staff in contact with multiple patients
Describe how antibiotic therapy can impair commensal flora?
Normally commensal organisms can outcompete pathogens for adhesion, metabolism and growth
After antibiotic therapy, the pathogen has no competition, leading to overgrowth
When the pathogen produces toxins damaging the host, this causes a symptomatic infection
How can we prevent the emergence of drug resistant bacteria and nosocomial infections? BE SICK
Broad spectrum reduction
Existing medication alteration
Strategies of prescription
Identifying infections quickly
Combinations of antibiotics and inhibitors
Knowledge of local strains
What are the three broad classes of conditions that fungi can cause in humans?
Allergy - allergic reactions to fungal products
Mycoses
Mycotoxicoses
What are mycoses?
Superficial, subcutaneous or systemic colonisation, invasion and destruction of human tissue
What are mycotoxicoses?
Ingestion of fungi and their toxic products
What gram-negative organism causes HA pneumonia, burn wounds and particularly affects the immunocompromised hosts and survives on abiotic surfaces?
Pseudomonas aeruginosa
What gram negative organism causes UTIs, and survives on abotic surfaces?
Acinetobacter baumannii
What gram-positive organism colonises the nasopharynx and causes blood stream infections and shows disseminated spread?
Staphylococcus aureus
What gram positive organism is a commensal of the gastrointestinal tract, but can also cause blood stream infections and UTIs?
Enterococcus
What gram positive organism is a major cause of antibiotic associated diarrhoea and mortality?
Clostridium
