Introduction to Antibiotics Flashcards

1
Q

Define antimicrobial

A

An antimicrobial is a chemical that inhibits the growth of, or kills, a micro-organism

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2
Q

Describe the spectrum of antimicrobials

A

Antimicrobials have a broad spectrum:
- they are active on a wide range of bacteria, viruses, fungi and or parasites

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3
Q

Contrast between broad and narrow spectrum antimicrobials, and explain when they are used

A

antimicrobials can be divided into broad spectrum, and narrow-spectrum antimicrobials
- broad spectrum anti-microbials are used when there is a suspected infection, or a proven infection with either:
- multiple organisms
- a single organism with AMR
- narrow spectrum anti- microbials are active on a limited number of bacteria, viruses, fungi or parasites
- used to target specific suspected or proven organisms, whilst minimising effect on normal flora

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4
Q

List the four types of antimicrobials

A
  • antiviral agent: a drug to treat a disease caused by virus
  • antifungal agent: a drug used to treat disease caused by a fungus
  • antiparasitic agent: a drug used to treat disease caused by a parasite
  • antibacteial agent or antibiotic: a drug to treat disease caused by bacteria
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5
Q

Describe the routes of administration of antimicrobials

A
  • oral
  • parenteral - intravenous or intramuscular
  • topical e.g. skin, mucous membranes (eye, oral cavity, vaginal)
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6
Q

Describe the sources of antibacterials

A

Antibiotics
may be one of two types:
- naturally produced by bacteria and fungi
- chemically modified from a naturally produced substance

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7
Q

Define selective toxicity

A

Selective toxicity:
- this refers to antibiotics that are active against specific targets in the bacterial cell, to reduce risk of adverse effects on the host

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8
Q

Define empirical treatment and explain what it entails

A

Empirical treatment refers to choosing an antibiotic based on the most likely bacteria causing the infection.
In order to do this, we need to:
- diagnose the syndrome (for example community acquired pneumonia)
- determine the most likely bacteria based on host and environmental factors
- determine most effective antibiotic to use based on the known antibiotic sensitivity data
- weigh up the risk of a narrow spectrum antibiotic (i.e. missing out on an organism) vs the risks of broad spectrum antibiotic (i.e. side effects and resistance)

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9
Q

Define empirical treatment and explain what it entails

A

Empirical treatment refers to choosing an antibiotic based on the most likely bacteria causing the infection.
In order to do this, we need to:
- diagnose the syndrome (for example community acquired pneumonia)
- determine the most likely bacteria based on host and environmental factors
- determine most effective antibiotic to use based on the known antibiotic sensitivity data
- weigh up the risk of a narrow spectrum antibiotic (i.e. missing out on an organism) vs the risks of broad spectrum antibiotic (i.e. side effects and resistance)

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10
Q

Define directed treatment and describe it

A

Directed treatment refers to choosing antibiotic based on results of microbiological culture, with or without antibiotic sensitivity test.
- it is not uncommon, however, if you cannot make a microbiological diagnosis, you have to continue with an empirical treatment.

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11
Q

Define directed treatment and describe it

A

Directed treatment refers to choosing antibiotic based on results of microbiological culture, with or without antibiotic sensitivity test.
- it is not uncommon, however, if you cannot make a microbiological diagnosis, you have to continue with an empirical treatment.

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12
Q

Describe the gram staining procedure

A
  1. Begin with heat fixed cells
  2. Flood slide with crystal violet dye for 1 minutes
  3. Add iodine solution for 1 minute
  4. Wash slide with alcohol for 20s
  5. Counter stain with safranin
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13
Q

Provide examples of Gram positive bacteria

A

Staphylococcus sp., Streptococcus sp. Enterococcus sp.

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14
Q

Provide some examples of Gram negative bacilli

A

Enterobacteriales sp., Psuedomonas aeruginosa, Haemophilus influenzae

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15
Q

Provide examples of strict anaerobes

A

Strict anaerobes can be divided into:
- above diaphragm e.g. mouth, lungs e.g. Fusobacterium sp.
- below diaphragm e.g. abdominal e.g. Bacteroides sp.

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16
Q

Provide some examples of atypical organisms

A
  • lacking cell wall e.g. Mycoplasma
  • unusual cell wall e.g. Mycobacterium

Other examples:
- Listeria - Gram positive bacillus
- Neisseria sp. - Gram negative cocci
- Syphilis (spirochete)

17
Q

List the broad classes of antibiotics

A

There are five broad classes of antibiotics, based on their bacterial cell target:
- cell wall synthesis:
- vancomycin
- bacitracin
- cell membrane: polymyxins
- b-lactams:
- penicillin
- cephalosporins
- carbapenems
- monobactams
- Nucleic acid synthesis:
- RNA polymerase: rifampin
- DNA gyrase: quinolones
- Folate synthesis:
- sulfonamides
- trimethoprim
- Protein synthesis e.g.
- 50S:
- macrolides
- linezolid
- clindamycin
- chloramphenicol
- streptogramins
- 30S:
- tetracyclines
- aminoglycosides

18
Q

Describe the mechanism of penicillin

A

Beta lactam antibiotics:
Examples include
- penicllin or aminopenicillin
- flucloxacillin or dicloxacillin
- cephalosporins
- amoxycillin clavulanate
- piperazine taxobactam -> moderately common in hospital
- carbapenems -> restricted use in hospitals

Glycopeptides e.g. vancomycin -> restricted use in hospitals.

All other listed proteins are common both in community and hospital setting.

Penicillin binding proteins:
- enzymes that catalyse the last steps of bacterial cell wall biosynthesis, resulting in peptide cross-linkages
- normally PBPs bind to terminal D-Ala-D-Ala residues of peptidoglycan precursors to carry out transpeptidation
- beta-lactam antibiotics are structurally similar to D-Ala-D-Ala, so they bind to PBPs, leading to inactivation
- the consequence is that it prevents peptide cross-links between peptidoglycan

  • a chemical modification of the basic structure results in different:
    • spectrum of activity: range of bacteria is effective against
    • toxicity: adverse effects
    • stability: from breakdown by body and/or bacteria

Note:
Bacterial resistance to b-lactam antibiotics:
- enzymes produced by bacteria which break down beta lactam antibiotics

Options for overcoming beta-lactamases:
- add another compound, which inhibits beta-lactamase
- make another antibiotic which is unaffected by the beta-lactamase

Beta lactamase inhibitors
- clavunate and amoxycillin -> augmentin
- tazobactam and piperacillin -> tazocin
- beta lactamase inhibitors irreversibly bind to beta lactamase
- beta lactam (+inhibitor) inhibitor kills beta lactamase-producing bacteria

19
Q

Provide some examples of beta lactamase inhibitors

A

Examples of beta lactamase inhibitors:
- penicillin - a narrow spectrum antibiotic - against Strep. spp., Enterococcus faecalis, above diaphragm anaerobes; others: syphilis, L. monocytogenes, N. meningitidis
- these bacteria are affected by beta-lactamases (penicillinases)
- amoxicillin - a moderate spectrum antibiotic - as per penicillin, plus some Gram negative activity (e.g. 50% E. coli)
- affected by beta-lactamases (penicillinases)
- flucloxacillin - a narrow spectrum antibiotic - against S. aureus, Strep. pyogenes (skin infections)
- unaffected by penicillinases
- amoxicillin-clavunate - a broad spectrum antibiotic - as per amoxicillin
- more Gram negative activity
- below diaphragm anaerobes
- S. aureus
- clavulanate inhibits some beta-lactamase, including penicillinases

20
Q

Describe the mechanism of action of cephalosporins

A

Cephalosporins
- broader spectrum antibiotics
- unaffected by penicillinases
- often given to patients with penicillin allergies

Examples include:
- first generation: cephalexin/cefazolin
- most Streptococcus and Staphylococcus
- some Gram negative, similar to augmentin
- no anaerobes, Listeria monocytogenes or Enterococcus spp.
- poor CSF penetration - don’t use for meningitis
- oral and intravenous
- second generation - cefotixin
- third generation: ceftriazone and ceftazidime
- more Gram negative cover
- good Streptococcus sp. cover
- less Staphylococcus sp. cover
- above diaphragm anaerobes only
- no Listeria monocytogenes or Enterococcus spp.
- adequate CSF penetration
- intravenous only
- fourth generation: cefepime
- broad spectrum
- including Pseudomonas aeruginosa
- above diaphragm anaerobes only
- No Listeria monocytogenes or Enterococcus spp.
- IV only

21
Q

List the four types of cephalosporins

A
  • first generation: cephalexin/cefazolin
    • most Streptococcus and Staphylococcus
    • some Gram negative, similar to augmentin
    • no anaerobes, Listeria monocytogenes or Enterococcus spp.
    • poor CSF penetration - don’t use for meningitis
    • oral and intravenous
  • second generation - cefotixin
  • third generation: ceftriazone and ceftazidime
    • more Gram negative cover
    • good Streptococcus sp. cover
    • less Staphylococcus sp. cover
    • above diaphragm anaerobes only
    • no Listeria monocytogenes or Enterococcus spp.
    • adequate CSF penetration
    • intravenous only
  • fourth generation: cefepime
    • broad spectrum
    • including Pseudomonas aeruginosa
    • above diaphragm anaerobes only
    • No Listeria monocytogenes or Enterococcus spp.
    • IV only
22
Q

List some other examples of beta lactam antibiotics

A

Other beta lactam antibiotics
- piper-tazobactam (tazocin)
- meropenem
- very broad spectrum including Pseudomonas spp.
- intravenous only
- restricted use in hospital to prevent antibiotic resistance emergence from overuse

23
Q

Describe the mechanism of glycopeptide antibiotics

A

Glycopeptide antibiotics
- bind to D-Ala-D-Ala
- prevents PBP access, therefore prevent peptide cross links
- vancomycin is not absorbed orally, thus is administered intravenously
- glycopeptide antibiotics are only effective against Gram positive bacteria
- frequently a last resort against antibiotic resistant Gram positive bacteria

24
Q

Describe the mechanism of action of protein synthesis inhibitors

A

Protein synthesis inhibitors
- aminoglycosides: block initiation of translaion and causes misreading of mRNA
- tetracyclines: blcok attachment of tRNA to ribosome
- macrolides: prevent continuation of protein synthesis
- streptogramins: each interferes with a distinct step of protein synthesis
- chloramphenicol: prevents peptide bonds from being formed
- lincosamides: prevent continuation of protein synthesis
- oxazolidinones: interfere with initiation of protein synthesis

25
Q

Describe the mechanism of action of aminoglycosides and provide some examples

A

Aminoglycosides
- works against aerobic Gram negative bacteria - not Gram positive, NOT anaerobes
- intravenous only
- toxicity: ototoxicity, and nephrotoxicity
e.g. gentamicin, tobramycin, amikacin

26
Q

Describe the mechanism of action of macrolides and give some examples

A

Macrolides
- good oral bioavailability - mainly used orally
- works against Gram positive bacteria
- but its main use is against atypical organisms e.g. Mycoplasma sp. and Chlamydia sp.
- useful for community acquired pneumonia and STIs e.g. erythromycin, clarithromycin, azithromycin

27
Q

Describe the mechanism of tetracyclines

A

Tetracyclines
- similar to macrolides: works against Gram positive bacteria
- but also useful for malaria
- NOT suitable for under 8 years
e.g. tetracycline, doxycycline, minocycline

28
Q

Describe the mechanism of action of lincosamides

A

Lincosamides
- good oral bioavailability
- mainly used orally
- works against Gram positive bacteria and anaerobes
- useful for Staph./Strep. infections when allergic to penicillins
- e.g. clindamycin, lincosamide

29
Q

Describe the mechanism of action of ciproflozacin

A

Examples of DNA synthesis inhibitors:
- ciprofloxacin
- nitroimidazoles
Examples of RNA synthesis inhibitors:
- rifampin

Ciprofloxacin:
- inhibit bacterial DNA replication by binding to, and inhibiting, DNA gyrase
- DNA gyrase relieves topological stress on DNA introduced during replication
- good oral bioavailability
- broad spectrum Gram negative bacteria, including P. aeruginosa
- some Staph. sp. cover but no Strep. sp. cover
- no aerobic cover

30
Q

Describe the mechanism of action of nitroimidazoles

A

Nitroimidazoles e.g. metronidazole, tinidazole
- anaerobic bacteria only
- also protozoa: trichomonas, giardia, entamoeba histolytica
- good oral bioavailability

31
Q

Folic acid synthesis

A

Nucleic acid inhibition - folic acid synthesis
Tetrahydrofolic acid (FH4) -> purines and pyrimidines -> DNA and RNA

32
Q

Describe the mechanism of action of trimethoprin and sulfonamides

A

Selective toxicity
- only bacteria contain the 1st half of the above pathway (dihydropteroate synthase) inhibited by sulphonamide
- bacterial dihydrofolate reductase has a significant greater affinity for trimethoprim (40,000 times greater) than the mammalian equivalent

33
Q

Note the spectrum of action of cotrimoxazole

A

Spectrum:
- Staph. sp.
- some Strep. sp.
- atypical bacteria - nocardia
- moderate Gram negative bacilli, and is commonly used for UTIs
- parasites: cyclospora, toxoplasmosis
- fungi: P. jiroveci

34
Q

List some mechanisms of antibiotic resistance

A

Mechanisms of antibiotic resistance:
- increased elimination: drug enters cell but efflux pump ejects it
- drug-inactivating enzyme: enzyme modifier drug, inactivating it
- alteration in target molecule: drug cannot bind target
- decreased uptake: porin proteins prevent entry into cell