Antibiotics Flashcards

1
Q

What are the causes of infection?

A
  • Bacteria
  • Fungi
  • Viruses
  • Parasites
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2
Q

What is bacteria and give some examples of some bacteria

A
  • 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
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3
Q

What is fungi and give some examples

A
  • 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
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4
Q

What is a virus and give some examples

A
  • 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!

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5
Q

What is a parasite and give some examples

A
  • 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
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6
Q

What is the difference between antibiotics and antiseptics?

A
  • 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

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7
Q

What exceptions are there to drugs that work on more than 1 group?

A
  • Exceptions:
    • Metronidazole active against flagellate parasites (‘Flagyl’) and strictly anaerobic bacteria
    • Co-trimoxazole active against bacteria and Pneumocystis jirovecii
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8
Q

How can we use antibiotics?

A
  • 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
  • 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
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9
Q

What are the major groups of antibacterials?

A
  • 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)
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10
Q

What do most antibacterials target?

A
  • 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
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11
Q

Draw a beta-lactam ring

A
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12
Q

Explain how beta lactams work

A
  1. Beta-lactam ring binds irreversibly to the enzymes that manufacture the bacterial peptidoglycan cell wall (‘penicillin-binding proteins’)
  2. Cell can’t make peptidoglycan
  3. Cell dies
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13
Q

Draw the anatomy of a bacterium

A
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14
Q

What is this condition?

Likely pathogens causing it?

What is the treatment & the alternative treatment?

A
  • Cellulitis
  • Likely pathogens:
    • Probably Streptococcus pyogenes
    • Possibly another pyogenic streptococcus or Staphylococcus aureus
  • Typical treatment:
    • Flucloxacillin
  • Alternatives:
    • Ceftriaxone
    • Clindamycin
    • Linezolid
    • Daptomycin
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15
Q

Explain how glycoproteins work (& example → main role)

A

E.g. vancomycin → for treating C.difficile

  • Cell wall activity:
    • molecule binds growing peptidoglycan cross-links
  • Only active against Gram positive organisms
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16
Q

Explain how macrolides work (& example → main roles)

A

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
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17
Q

What condition, pathogen, treatment would this patient have?

A
  • Community-acquired pneumonia
  • Likely pathogens:
    • Streptococcus pneumoniae
    • Haemophilus influenzae
    • but could be Legionella etc
  • Typical treatment:
    • co-amoxiclav plus
    • clarithromycin
18
Q

Explain how tetracyclines work and examples & main roles

A

e.g. tetracycline, doxycycline

  • Bind to bacterial ribosomes
    • prevent protein synthesis > stops cell growing/dividing
  • Good for respiratory infections, skin conditions (acne)
19
Q

Explain how aminoglycoside work and give examples & main roles

A

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
20
Q

Explain how quinolones work and examples & main roles

A

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

21
Q

What are some antifungal drugs?

A
  • Imidazoles
  • Triazoles
  • Echinocandins
22
Q

What is this condition?

A

Thrush/Oral Candida

23
Q

What is this condition?

A

Ringworm

24
Q

Give examples of some antiviral drugs

A
  • Aciclovir
  • AZT for HIV
  • Oseltamivir for influenza
  • remdesivir for COVID-19
25
Q

Give examples of antiparasitic drugs and what they are used for

A
  • 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
26
Q

Why does antibiotic resistance happen?

A
  • 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
27
Q

What is this condition?

A
  • Paronychia
    • With a pustule
28
Q

What is the current treatment for gonorrhoea?

A
  • IM ceftriaxone
29
Q

What are the mechanisms of acquired resistance?

A
  • 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
30
Q

Why is antimicrobial resistance a bad thing?

A
  1. Infections are harder to treat → need more toxic, more expensive, less convenient agents
  2. Infections can be more severe
    1. delayed optimisation of treatment
    2. virulence often linked to resistance
  3. Infections can be more common
    1. failure of prophylaxis
    2. vicious circles related to virulence and colonisation resistance
31
Q

How can we prevent antibiotic resistance?

A
  • Global coalition (e.g. agriculture, new drugs)
  • Demand: reduce antibiotic use (patient education → more in PRIMARY CARE, surveillance, restrictions)
  • Supply: develop new antibiotics
32
Q

What is antibiotic stewardship?

A
  • 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)
33
Q

Explain C.diff and what the approaches are to minimise it?

A
  • 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
34
Q

When to do if someone says they have an allergy to penicillin?

A
  • Don’t take this at face value, always explore:
    • vomiting / diarrhoea / dyspepsia – intolerance not allergy
    • rash – cephalosporins probably ok
    • anaphylaxisavoid all beta-lactams, use something else
    • 10% of people think they are allergic to penicillin, only 1% really are
35
Q

What to do when someone has a UTI?

A
  • 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)
36
Q

What are some symptoms of a UTI?

A
37
Q

What to do when someone has bronchitis?

A
  • 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
38
Q

What to do if someone has a skin infection like this:

A
  • 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
39
Q

What to do if someone has endocarditis?

A
  • 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
40
Q

What to do if someone has bacterial meningitis?

A
  • 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