Antimicrobial teaching Flashcards
What are the main causes of infection?
Bacteria
Fungi (yeasts and moulds)
Viruses
Parasites
What is a bacteria?
Bacteria are a domain of taxonomy
Single celled organism with phospholipid bilayer membranes
Only a subset infect humans - staph.aureus, E.coli, strep.pneumonia
What are fungi?
Are eukaryotes
Have a cell wall, can be classified as yeasts or moulds.
Only a subset infection humans - candida, aspergillus.
What is a virus?
What are some common causes of infection in humans?
Viruses replicate inside living cells of a cellular organism.
Only a subset infect humans - SARS-2 coronavirus, Influenza, measles, EBV.
What is included as a parasite?
What are the different types?
An organism that lives on or in another organism and thrives on nutrients from the host as the host expense.
Protozoa - (singled celled typically found in infected food/water) plasmodium, amoebae
Helmiths - (multicellular typically found in the digestive system) tapeworm, flatworms
Ecroparastites - (multicellular, found on skin, live off blood etc)arthropods, lice, mites etc
What is the basic difference between antibiotics and antispetics?
Antibiotics - bind to specific targets, typically treat established infections.
Antiseptics - act more generally, typically clean surfaces/skin
What drugs tend to be active against multiple different causes (viral, bacterial, fungal etc) causes of infection?
Metronidazole = flagella parasites and anaerobic bacteria
Co-trimoxazole = bacteria and pneumocystis jirovecii.
What are the different clinical ways that antibiotics mat be used?
Treatment - curative ‘course’ or suppressive (tends to be indefinite)
Prevention - prophylaxis before the event or pre-emptive therapy after exposure.
What empirical treatment is used for urosepsis?
Co-amoxicalv +/- gentamicin for suspected urosepsis.
What is meant by broadening antibiotic treatment?
Often called escalation
Patient not improving - possibility of treatment failure - changing to a broader spectrum agent
Very often failure to improve is not because of antibiotic failure
What is meant by the term changing antibiotic use?
Response to new information suggesting that current treatment won’t work.
For example cultures show resistance to antibiotics being used
What is meant by the term narrowing antibiotic use?
Sometimes called de-escalation
Taking opportunity to change to a safer or more targeted agent
Seeking to maintain activity but reduce risks.
What are the different types of beta-lactams?
Give an example of each
Penicillins - amoxicillin
Cephalosporins - ceftazidime
Monobactams - aztreonam
Carbapenems - imipenem
Generall cell wall targeting antibiotics are xxxx and ribosomal agents are xxxx.
Bacteriocidal
Bacteriostatic
What is the basic mechanism of action of beta-lactams?
Chem - contains a beta lactam ring
Inhibits systhesis of the peptidoglycan layer, by covalents/irrevesibly dining to and inhibiting the action of transpeptidase enzymes (PBPs) which are involved in cross linking.
This disruption weakens the cell wall, leading to bacterial lysis and death.
What pathogens typically cause cellulitis?
Streptococcus pyogenes
Or staphylococcus aureaus
What is the typical antibiotic treatment used for cellulitis?
Flucloxacillin - first line
Alternatives: ceftriaxone, clindamycin.
What are some example glycopeptides?
Vancomycin
Teicoplanin
Dalbavancin
Oritavancin
What is the action of glycopeptides?
Only active against gram-positive organisms.
Not absorbed PO.
Inhibits bacterial cell wall synthesis by binding to the D-ala-D-ala terminus of peptidoglycan precursors, preventing incoporoprtation into the growing cell wall.
What are the typically used of a glycopeptide antibiotic?
Vancomycin is used PO for C.difficile infections
Vancoycin and tecioplanin can be for line-related infections (norm beta lactam resistance gram positives)
What are some examples of macrolides?
Macrolides - erythromycin, clarithromycin.
Azalides - azithromycin
Lincosamides - clindamycin
What is the basic mechanism of action of macrolides?
Bind to 50S ribosomal subunit
It inhibits protein synthesis by blocking the polypeptide exit tunnel, which prevents peptide chain prolongation.
Leads to the production of the short peptides of 3-9 amino acids.
Prevents cell division/growth
What are the main indications for macrolides?
Alternatives to penicillins in many situations
Specific use:
Legionella and other atypical pneumonia
Chlamydia trachomatis
Azithromycin - resp prophylaxis
Clindamycin - 2nd line in cellulitis.
What antibiotic classes tend to be used to treat pneumonia?
A beta lactam +/- a macrolide
Give some examples of tetracyclines?
(oxy)tetracycline, doxycyline
Lymecycline, minocycline
Tigecycline
What is the basic mechanism of action of tetracyclines?
Block protein synthesis by binding to the 30S ribosomal subunit of bacteria
Inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex.
Inhibits the addition of new amino acids - stopping protein synthesis
What is the main role/indication of tetracyclines?
Good for PO treatment of resp infections.
OK for skin/soft tissue infections
Useful for long term use e.g acne, suppressive therapy
Should not be given to children, pregnant and breast feeding women as negative effect on bone/teeth development.
Give some examples of aminoglycosides.
Gentamicin
Netilmicin
Tobramycin
Amikacin
Neomycin
Streptomycin
What is the basic moa of aminoglycosides?
Bind to the aminoacyl site of 16s rRNA within the 30S ribosomal subunit
Induces codon misreading and mistranslation of proteins which results in the production of polypeptides containing incorrect aminoacids, damaging the bacterial cell membrane.
What are the main uses/indications of aminoglycosides?
Not often used in isolation - maybe in UTI
Additive effect e.g UTI or neutropenic sepsis
Synergistic effect - streptococcal endocarditis
To defer an escalation decision
Give some examples of quinolones
Ciprofloxacin
Ofloxacin
Moxifloxacin
Delafloxacin
What is the basic moa of quinolones?
Inhibits the activity of DNA gyrase and topoisomerase 4.
Results in fatal DNA breaks.
What is main role/indication of quinolones?
Increasing restricited by side effects. (serious include: tendon rupture, GAIT abnormalities, CNS disturbances)
Generally used when no other options are well absorbed PO.
Why are fungi harder to treat than bacterial infections?
Fungi are eukaryotes
No peptidoglycan cell wall
Ribosomes are less distinct from our own
More difficult to find drug targets.
What are some example antifungal drugs?
Imidazoles (clortimazole)
Triazoles (fluconazole)
Echinocandins - caspofungin
Polyenes - amphotericin B, Nystatin
What is the basic concept of anti-viral treatment?
Viruses replicate inside host cells - more difficult to target them selectively.
Emphasis on supportive management (common cold, glandular fever) or prevention (vaccination, lifestyle etc)
What antiviral tends to be used for HSV and VSV?
Aciclovir
What antiviral tends to be used for CMV?
Ganciclovir
What antivirals tend to be given for HIV?
Anti-retrovirals
What anti-viral tends to be given for influenza?
Oseltamivir
What antiviral is sometimes given for COVID-19?
Paxlovid
What are some common anti-parasitic drugs in the UK?
What are they used for?
Mebendazole for threadworms
Permethrin or malathion for head lice and scabies.
What is the basic mechanism of antimicrobial resistance?
Antibiotics act as a selective pressure.
Random mutation occurs in bacteria - better adapted to environment, survival advantage
More likely to replicate - genes passes to offspring - eventually spread throughout the population to become the dominant feature.
As bacteria replicate rapidly - properties can spread quickly.
What factors have contributed to the rapid development of antimicrobial resistance?
Increased used of antibiotics
Prescriptions taken incorrectly
Sold without medical supervision
Prophylactic use before surgery
Spread of resistance microbes in hospitals due to lack of hygiene
Patient who do not complete the course
Antibiotics in animal feeds.
What are some of the consequences of antimicrobial resistance?
Infection are harder to treat - need more toxic, expensive, less convenient agents
Infections can be more severe - related optimisation of treatment, virulence often linked to resistance
Inflectsion can be more common - failure of prophylaxis, vicious circles related to virulence and colonisation resistance.
What are main mechanism that bacterial use to show resistance against antimicrobials?
- Bestroy the antibiotic - beta-lactamases or aminoglycoside modifying enzymes
- Bacterium modifies target - PBP in MRSA, ribosomal structure
- Reduced permeability - klebsiella and ertapenem
- Efflux pumps - reduced conc of antibiotic.
Give some examples of beta-lactamse inhibitors?
Co-amoxiclav - amoxicillin plus clavulanic acid
Zoysn - piperacillin plus tazobactam
Ceftazidmine plus avibactam
What are some potential consequences of antimicrobial resistance in health care?
‘Pan-resistance’ will become more common = species resistant to all anti-microbial treatment
Levels fo resistance too high to rely on empiric treatment - either preventative or treatment.
What are some important global response to antibiotic resistance?
Agreements about antibiotic use in agriculture
Environmental standards re antibiotic pollution
Development of new drugs
What are some national responses to antibiotic resistance?
Surveillance
Patient education
Prescribing restrictions
What are some local responses to antibiotic resistance?
Infection control
Antimicrobial stewardship.
What is meant by antimicrobial stewardship?
Things we do to optimise the treatment of current patients without compromising the care of future patients.
(use antibiotics less, use antibiotics better)
How can healthprofessionals help use antibiotics less?
Taking all opportunities to prevent infection
Raising the bar re certainnity of bacterial infection before prescribing
Watchful waiting, rescue prescribing etc
Shorter courses (but not lower doses)
How can we use antibiotics better?
Using narrower spectrum agents
Using agents less likely to promote resistance.
What infections often occur after antibiotic use?
Clostridiodes difficile infection
How can we help reduce C.Diff infection?
Clean healthcare environment - chlorine better than detergent.
Don’t give it to people - wash your hands, wash your equipment
Isolate cases +/- carriers
Antimicrobial stewardship.
What antibiotics can be used to treat bronchitis?
Want to cover haemophilus influenxa, streptococcus pneumonia and moraxella catarrhalis.
Want something well tolerated and preferably cheap
Doxycyline, amoxicillin, clarithromycin.
What antibiotics are typically given to treat skin infections?
Want to cover staph aureus and streptococci
Flucloxacillin, doxycyline, clarithromycin
What antibiotics tend to be given to treat endocarditis?
Want to cover alpha-hemolytic streptococci
Maybe staphylococci and enterococci
Bacteriocidal and available IV: high dose amoxicillin plus gentamicin
Vancomycin plus gentamicin
What antibiotics are typically given to treat bacterial meningitis in adults?
IV, crosses BBB and bacteriocidal
Must cover neisseria meningititidis, streptoccus pneumonia +/- listeria monocytogenes
Typically cefotaxmime +/- amoxicillin.
How is antimicrobial resistance spread?
May be intrinsic - aka never susceptible
Acquired:
Vertical - mutation, selective pressure and survival advantage to offspring
Transfer of resistance genes - plasmids, bacteriophage, free DNA
Growth conditions - biofilms, swarming, persisters
