Introduction to Antibiotics Flashcards
(34 cards)
Define antimicrobial
An antimicrobial is a chemical that inhibits the growth of, or kills, a micro-organism
Describe the spectrum of antimicrobials
Antimicrobials have a broad spectrum:
- they are active on a wide range of bacteria, viruses, fungi and or parasites
Contrast between broad and narrow spectrum antimicrobials, and explain when they are used
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
List the four types of antimicrobials
- 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
Describe the routes of administration of antimicrobials
- oral
- parenteral - intravenous or intramuscular
- topical e.g. skin, mucous membranes (eye, oral cavity, vaginal)
Describe the sources of antibacterials
Antibiotics
may be one of two types:
- naturally produced by bacteria and fungi
- chemically modified from a naturally produced substance
Define selective toxicity
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
Define empirical treatment and explain what it entails
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)
Define empirical treatment and explain what it entails
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)
Define directed treatment and describe it
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.
Define directed treatment and describe it
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.
Describe the gram staining procedure
- Begin with heat fixed cells
- Flood slide with crystal violet dye for 1 minutes
- Add iodine solution for 1 minute
- Wash slide with alcohol for 20s
- Counter stain with safranin
Provide examples of Gram positive bacteria
Staphylococcus sp., Streptococcus sp. Enterococcus sp.
Provide some examples of Gram negative bacilli
Enterobacteriales sp., Psuedomonas aeruginosa, Haemophilus influenzae
Provide examples of strict anaerobes
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.
Provide some examples of atypical organisms
- 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)
List the broad classes of antibiotics
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
Describe the mechanism of penicillin
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
Provide some examples of beta lactamase inhibitors
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
Describe the mechanism of action of cephalosporins
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
List the four types of cephalosporins
- 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
List some other examples of beta lactam antibiotics
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
Describe the mechanism of glycopeptide antibiotics
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
Describe the mechanism of action of protein synthesis inhibitors
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
