Antibiotics Flashcards
What are the causes of infection?
- Bacteria
- Fungi
- Viruses
- Parasites
What is bacteria and give some examples of some bacteria
- Single celled organisms with phospholipid bilayer membranes
- Only a tiny subset infect humans e.g.
- Staphylococcus aureus
- Escherichia coli
- Streptococcus pneumoniae
- Campylobacter jejuni
- Mycobacterium tuberculosis
- Yersinia pestis
What is fungi and give some examples
- Fungi (type of eukaryote): Usually divided into moulds vs yeasts
- no peptidoglycan cell wall
- ribosomes are less distinct from our own
- more difficult to find drug targets
- Only a subset infect humans, eg:
- Candida sp.
- Aspergillus sp.
- Dermatophytes eg Trichophyton interdigitale
What is a virus and give some examples
- Viruses: Replicate inside living cells of a cellular organism
- Hence, difficult to target them selectively (thus, supportive management and prevention → important)
- All cellular organisms have viruses, including Archaea and Bacteria
- Only a subset infect humans, eg:
- SARS-2 coronavirus
- Influenza virus
- Measles virus
- HIV, EBV, CMV, hepatitis viruses
Not included in the three-domain system because non-cellular!
What is a parasite and give some examples
- Parasites: Loose term covering various not-closely-related, multicellular organisms eg
- Protozoa: Plasmodium malariae, Trypanosoma brucei, amoebae
- Helminths: tapeworms, flatworms, roundworms
- ‘Ectoparasites’: lice, mites, fleas
What is the difference between antibiotics and antiseptics?
- Antibiotics: Broadly, drugs that kill* pathogens *without killing people
- Overlap between antibiotics and antiseptics, but essentially antibiotics bind to specific targets while antiseptics act more generally
Antibiotic: technically a naturally-occurring rather than a man-made antimicrobial but in practice the terms are synonymous
What exceptions are there to drugs that work on more than 1 group?
-
Exceptions:
- Metronidazole active against flagellate parasites (‘Flagyl’) and strictly anaerobic bacteria
- Co-trimoxazole active against bacteria and Pneumocystis jirovecii
How can we use antibiotics?
-
Treatment of infection
- Curative – ‘course’ of varying length
- Suppressive – often indefinitely
-
Prevention of infection
-
Before the infective event:
- prophylaxis – usually single dose
- eg operative prophylaxis
-
After the infective event:
- technically ‘pre-emptive therapy’ – single dose or short course
- eg meningococcal contact ‘prophylaxis’, bite injuries
-
Before the infective event:
-
Empiric therapy
- ‘Best guess’
- eg co-amoxiclav +/- gentamicin for suspected urosepsis
-
Targeted therapy
- Directed against a specific organism
- eg blood cultures growing E. coli susceptible to amoxicillin
What are the major groups of antibacterials?
- Beta-lactams
- penicillins (amoxicillin, flucloxacillin) → end in -cillin
- cephalosporins (cefalexin,cefuroxime) → start with cef-
- (monobactams → aztreonam)
- carbapenems (imipenem, meropenem)
- Macrolides/azalides/lincosamides
- Tetracyclines (end in -cycline)
- Aminoglycosides
- Quinolones
- Glycopeptides
- Others:
- trimethoprim (UTI), nitrofurantoin (UTI), fosfomycin (UTI), colistin/colomycin (last resort for Gram -ve), chloramphenicol (eyes), linezolid (allergies OR MRSA infections), metronidazole (against strict anaerobes), rifampicin (TB)
What do most antibacterials target?
- Target one of:
- Cell wall (peptidoglycan)
- Protein synthesis (ribosomes)
- A few target:
- DNA replication
- cell membrane
- folate metabolism
- Generally (not always):
- Cell wall agents are bacteriocidal
- Ribosomal agents are bacteriostatic
Draw a beta-lactam ring
Explain how beta lactams work
- Beta-lactam ring binds irreversibly to the enzymes that manufacture the bacterial peptidoglycan cell wall (‘penicillin-binding proteins’)
- Cell can’t make peptidoglycan
- Cell dies
Draw the anatomy of a bacterium
What is this condition?
Likely pathogens causing it?
What is the treatment & the alternative treatment?
- Cellulitis
- Likely pathogens:
- Probably Streptococcus pyogenes
- Possibly another pyogenic streptococcus or Staphylococcus aureus
- Typical treatment:
- Flucloxacillin
- Alternatives:
- Ceftriaxone
- Clindamycin
- Linezolid
- Daptomycin
Explain how glycoproteins work (& example → main role)
E.g. vancomycin → for treating C.difficile
- Cell wall activity:
- molecule binds growing peptidoglycan cross-links
- Only active against Gram positive organisms
Explain how macrolides work (& example → main roles)
E.g. erythromycin, clarithromycin (usually alternative to penicillins e.g. legionella & chlamydia trachoma’s & atypical pneumonias)
- Bind to bacterial ribosomes
- prevent protein synthesis > stops cell growing/dividing
What condition, pathogen, treatment would this patient have?
- Community-acquired pneumonia
- Likely pathogens:
- Streptococcus pneumoniae
- Haemophilus influenzae
- but could be Legionella etc
- Typical treatment:
- co-amoxiclav plus
- clarithromycin
Explain how tetracyclines work and examples & main roles
e.g. tetracycline, doxycycline
- Bind to bacterial ribosomes
- prevent protein synthesis > stops cell growing/dividing
- Good for respiratory infections, skin conditions (acne)
Explain how aminoglycoside work and give examples & main roles
e.g. gentamicin
- Given IV OR topically
- Bind to bacterial ribosomes
- Prevent protein synthesis > stops cell growing/dividing
Main roles
- Not often used in isolation these days, though could do for UTI
- Usually used in combination e.g.
- UTI OR neutropenic sepsis
- Streptococcal endocard itis
Explain how quinolones work and examples & main roles
E.g. ciprofloxacin
How work
- Bind to topoisomerase IV / DNA gyrase–DNA complexes
- prevents DNA replication > stops cell growing/dividing
Main roles
- Increasingly restricted* by side effects generally used when *no other options
well absorbed PO
What are some antifungal drugs?
- Imidazoles
- Triazoles
- Echinocandins
What is this condition?
Thrush/Oral Candida
What is this condition?
Ringworm
Give examples of some antiviral drugs
- Aciclovir
- AZT for HIV
- Oseltamivir for influenza
- remdesivir for COVID-19
Give examples of antiparasitic drugs and what they are used for
- Mebendazole for threadworms (in caecum → lay eggs then eggs into anus → causes itching bum → spread to others)
- Permethrin or malathion for head lice and scabies
Why does antibiotic resistance happen?
- Pathogens are living things and evolve in response to selective pressure
- They become resistant to antibiotics!
- There are fewer and fewer new antibiotics coming to market
What is this condition?
-
Paronychia
- With a pustule
What is the current treatment for gonorrhoea?
- IM ceftriaxone
What are the mechanisms of acquired resistance?
-
Bacterium destroys the antibiotic
- beta-lactamases
- aminoglycoside modifying enzymes
-
Bacterium modifies its target
- penicillin-binding proteins in PRP
- peptidoglycan structure in VRE
- ribosomal proteins in macrolide and tetracycline resistance
-
Bacterium shuts the door
- reduced permeability eg ertapenem resistance in Klebsiella
-
Bacterium pushes it out
- efflux pumps
Why is antimicrobial resistance a bad thing?
- Infections are harder to treat → need more toxic, more expensive, less convenient agents
- Infections can be more severe
- delayed optimisation of treatment
- virulence often linked to resistance
- Infections can be more common
- failure of prophylaxis
- vicious circles related to virulence and colonisation resistance
How can we prevent antibiotic resistance?
- Global coalition (e.g. agriculture, new drugs)
- Demand: reduce antibiotic use (patient education → more in PRIMARY CARE, surveillance, restrictions)
- Supply: develop new antibiotics
What is antibiotic stewardship?
- Things we do to optimise the treatment of current patients without compromising the care of future patients
- Guidelines
- Better diagnostics
- Prescriber education
- Patient education
- Use antibiotics LESS (only when needed → when addvised by microbiologist)and use them BETTER (using narrower spectrum antibiotics)
Explain C.diff and what the approaches are to minimise it?
-
Clostridioides difficile infection
- An ecological side effect of antibiotic use
Approaches
- Clean healthcare environment
- chlorine better than detergent
- Don’t give it to people
- wash your hands
- clean your equipment
- Isolate cases
- +/- carriers
- Antimicrobial stewardship
When to do if someone says they have an allergy to penicillin?
- Don’t take this at face value, always explore:
- vomiting / diarrhoea / dyspepsia – intolerance not allergy
- rash – cephalosporins probably ok
- anaphylaxis – avoid all beta-lactams, use something else
- 10% of people think they are allergic to penicillin, only 1% really are
What to do when someone has a UTI?
- Manage symptomatically
- take a sample, wait and give targeted treatment
- treat empirically
- want to cover E. coli and other ‘coliforms’
- want something well absorbed PO
- want something well tolerated and preferably cheap:
- nitrofurantoin
- trimethoprim
- (refer to previous cultures)
What are some symptoms of a UTI?
What to do when someone has bronchitis?
- Manage symptomatically
- take a sample, wait and give targeted treatment
- treat empirically
- want to cover Haemophilus influenza, Streptococcus pneumonia and Moraxella catarrhalis
- want something well absorbed PO
- want something well tolerated and preferably cheap:
- doxycycline
- amoxicillin
- clarithromycin
What to do if someone has a skin infection like this:
- Manage symptomatically
- take a sample, wait and give targeted treatment
- treat empirically
- want to cover Staph aureus, streptococci
- want something well absorbed PO
- want something well tolerated and preferably cheap
- flucloxacillin
- doxycycline
- clarithromycin
What to do if someone has endocarditis?
- Manage symptomatically (rare, will have night sweats non-specific symptoms as bacteria from the valves breaks off and gets into the blood stream)
- take a sample, wait and give targeted treatment
- treat empirically
- want to cover alpha-haemolytic streptococci
- in some scenarios want to cover staphylococci and enterococci
- need something bacteriocidal and available IV
- high dose amoxicillin plus gentamicin
- vancomycin plus gentamicin
What to do if someone has bacterial meningitis?
- Manage symptomatically
- DO A LUMBAR FUNCTURE
- take a sample, wait and give targeted treatment
- treat empirically
- want to cover Neisseria meningitidis, Streptococcus pneumoniae +/- Listeria monocytogenes (when pregnant/immunocompromised)
- need something IV, which crosses BBB and bacteriodical
- typically cefotaxime +/- amoxicillin
