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Year 3 Lecture Content > Antimicrobials > Flashcards

Antimicrobials Flashcards

1
Q

BACTERIAL CELL WALL and MEMBRANE

areaffected by what type of antibiotics?

A

Beta lactam antibiotics -> · Penicillins · Cephalosporins · Carbapenems · Monobactams · Glycopeptides · Polymxins

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2
Q

NUCLEIC ACID SYNTHESIS is interuppted by what antibiotics

A

Folate anatgonists DNA gyrase · Quinolones RNA polymerase · Rifmycins (Rifampicin)

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3
Q

PROTEIN SYNTHESIS

50S subunits affected by?

A

· Macrolides · Lincomycins (Clindamycin) · Oxozolidinones (Linezolid) · Chroamphenicol (Chlorampehnicol)

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4
Q

Protein synthesis affecting 30S subunits are

A

· Tetracyclines · Aminoglycosides

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5
Q

What is the difference between bacteriostatic and bactericidal?

A

BACTERIOSTATIC antibiotics inhibit the growth and replication of bacteria (non-lethal) Eg. inhibitors of folate synthesis, quinolones

BACTERICIDAL antibiotics kill bacteria (lethal), but note that at low concentration these antibiotics may only be bacteriostatic Eg. penicillin, aminoglycosides

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6
Q

What is the core structure of penicillin?

What is the use of the side chain?

A

B-lactam

Side chain - absorption

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7
Q

What are 5 classes of penicillin?

A

5 classes of penicillin:

  • Natural penicillins
  • Penicillinase-resistant penicillins(staph infection)
  • Aminopenicillins(gram positive and gram neg - ecoli,hinfluenza)
  • Carboxypenicillins(pesudomonal-> pseudomonas, enteroccocus, Klebsiella)
  • Acyl ureidopenicillins(pseudomonas aeroginosa)
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8
Q

Penicillins

Are they broad or narrow spec?

Absorption level is good or bad?

Is it safe in pregnancy?

A

Narrow spectrum

Excellent absorption

Safe in pregnancy

  • Penicillin V
  • Amoxicillin
  • Flucloxacillin
  • Benzylpenicillin
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9
Q

Cephalosporins

Are they broad or narrow spec?

Absorption level is good or bad?

Is it safe in pregnancy?

A

Broad spectrum

Safe in pregnancy

• Cefuroxime • Ceftaxime • Ceftazidime

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10
Q

Carbapenams

Are they broad or narrow spec?

Can they be taken orally or IV?

Is it safe in pregnancy?

A

Broad spectrum

IV only Safe in pregnancy

• Meropenem • Ertapenem • Imipenem

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11
Q

Monobactams

What is the one licenced monobactam called?

A

Only one licensed monobactam (Aztreonam)

mainly for severe aerobic gram-negative bacillary infections (including meningitis) in patients who have a serious beta-lactam allergy

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12
Q

•Glycopeptides

Narrow or broad spec?

When is it IV and when is it oral?

is it safe in pregnancy

Examples of it.

A

Narrow spectrum

IV only – except CDiff (need oral)

Safe in pregnancy

• Vancomycin • Teicoplanin • (Dalbavancin)

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13
Q

Polymyxins (colistin) side effect and what bacteria is it used in

A

nephrotoxic

pseudomonas

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14
Q

What is the MOA of sufonamide and trimethoprim?

A

Broad spectrum

Often used in combination for SYNERGISTIC effects (Sulfamethoxazole plus trimethoprim, TMP/SMX)

Bacteriostatic

Not safe in pregnancy

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15
Q

DNA gyrase • Quinolones

A

Broad or narrow spectrum Excellent bioavailability • Ciprofloxacin • Levofloxacin • Ofloxacin • Gatafloxacin

Can cause problems with pregnancy

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16
Q

RNA polymerase = Rifamycins (Rifampicin)

What is it a potent inducer of ?

Is it safe in pregnancy?

can it be used alone?

What is it used for?

A

Semisynthetic derivative of rifamycin B produced by Streptomyces mediterranei

Potent liver inducer and significant interactions

Safe in pregnancy

Never used alone due to low genetic barrier (RpoB gene)

Used in few conditions • Tuberculosis • Prosthetic joint infections

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17
Q

Macrolides

Broad or narrow?

Bacteriostatic or cidal

Examples?

A

Broad spectrum

Bacteriostatic

• Erythromycin • Azithromycin • Clarithromycin

18
Q

Lincosamide (Clindamycin)

What type of bacteria does it kill?

What is it’s bioavailbility like

A

Gram positive and anaerobic infections

Excellent bioavailability

Bacteriostatic or bactericidal depending on dose and organism

19
Q

Oxazolidinones (Linezolid)

What type of bacteria does it kill

What is it’s bioavailability like

Is it bacteriostatic or cidal

A

Gram positive infections

Excellent bioavailability

Bacteriostatic

20
Q

• Chloramphenicol (Chloramphenicol)

Broad or narrow?

Usual mode of delivery?

Does it penetrate CNS

is it bacteriostatic or bacteriocidal?

A

Broad spectrum

Topical treatment

CNS penetration

Bacteriostatic

21
Q

Tetracyclines

Broad or narrow spec

Bacteriostatic or cidal

Safe in pregnancy?

Examples

Side effect?

A

Broad spectrum

Bacteriostatic

Not safe in pregnancy, breastfeeding and children

  • Doxycycline
  • Tetracycline
  • Minocycline

Side effect: stained teeth. Angioedema; diarrhoea; headache; Henoch-Schönlein purpura; hypersensitivity; nausea; pericarditis; photosensitivity reaction; skin reactions; systemic lupus erythematosus exacerbated; vomiting

22
Q

Aminoglycosides(gentamycin)

broad or narrow

A

Narrow spectrum

gram negative infections (and second-line TB Rx)

IV (or Neb tobramycin)

• Gentamycin • Amikacin • Tobramycin • Streptomycin

23
Q

Define the following causes of in vitro antibiotic effectiveness

Minimum inhibitory concentration (MIC)

MINIMUM BACTERICIDAL CONCENTRATION (MBC)

Detection of resistance mutation is done by?

A

MINIMUM INHIBITORY CONCENTRATION (MIC) is the minimum in vitro concentration which an antibiotic can inhibit growth

MINIMUM BACTERICIDAL CONCENTRATION (MBC) is the minimum in vitro concentration which an antibiotic can kill bacteria​

The detection of RESISTANCE MUTATIONS by PCR

24
Q

In vivo antibiotic effectiveness depend on?

A

Pharmacokinetics

Pharmacodynamics

Drug interactions

Foreign material

Source control

Host immune responses

25
Q

Define bioavailability and which antibiotics are excellent?

A

BIOAVAILABILITY of oral agents is the proportion of drug absorbed into systemic circulation

Excellent (>90%): • Amoxicillin • Linezolid • Clindamycin • Levofloxacin • Ciprofloxacin • Rifampicin • Metronidazole

26
Q

VOLUME OF DISTRIBTUTION

A

relates the [drug]blood relative to the dose given

  • Small volume of distribution (plasma bound)
  • Large volume of distribution (fat soluble)
27
Q

Which drugs is a CYP3A4 inducer?

Which antibiotic is a CYP3A4 inhibitor?

A
  • CYP3A4 inducers (Rifampicin)
  • CYP3A4 inhibitors (Ketoconazole, Clarithromycin)
28
Q

HALF-LIFE

How is ceftriaxone excreted

How is azithromycin excreted?

A

of the drug is the time

taken for [drug]blood to reduce by 50% from Cmax

  • Renal excretion
  • Non-renal excretion
  • Biliary (Ceftriaxone)
  • Gut (Azithromycin)
29
Q

Give examples of concentration dependent killing(cmax/mic ratio), Time dependent killing (AUC/MIC ratio), Exposure dependent killing (AUC 24/ratio)

A

CONCENTRATION dependent killing (Cmax/MIC ratio) means drug PK needs to reach high drug concentration above the MIC

TIME dependent killing (AUC/MIC ratio) means drug PK needs to spend time above the MIC

EXPOSURE dependent killing (AUC24/ratio)

30
Q

POST-ANTIBIOTIC EFFECT (PAE)

A

is the time when bacterial growth is still inhibited when [drug]

31
Q

18yo normally healthy female in A&E admitted with

• Fever, dysuria, polyuria, flank pain and hypotension

A

Rx Co-amoxiclav and stat dose Gentamycin(Gentamycin so works quickly and then the comoxiclav works slower but longer)

32
Q

Antimicrobial resistance (AMR)

A

is the ability of a microbe to resist the effects of medication that once could successfully treat the microbe

33
Q

Main mechanisms of AMR

What are the 3 big resistant pathogens?

A
  1. Production of enzymes
  2. Changes to target sites or metabolic pathways
  3. Efflux pumps

Methicillin-resistant Staphylococcus aureus (MRSA)

Vancomycin-resistant Enterococci (VRE)

Extended-spectrum β– lactamase producing Enterobacteriaceae (ESBL)

34
Q

How do you combact mutation of enzymes - b lactam specifically

A

β-lactamase enzyme and hydrolysis of the β-lactam molecule

Use of decoy substrates • Amoxicillin/clavulanic acid • Piperacillin/tazobactam • Ceftazidime/avibactam Carbapenamase enzymes

35
Q

Changes to target sites or metabolic pathways

b-lactams

Macrolides and lincosomides

Quinolones

Carpapenams

Folate antagonist

A

Mutations in PBPs that stop binding (β-lactams)

Methylation of rRNA (macrolides and lincosomides)

Mutations in the gene for DNAgyrase (quinolones)

Mutations in porin channels (carbapenems)

Use of exogenous thymidine or thymidine for DNA synthesis (folate antagonists)

36
Q

What have bacteria developed against tetracylins:

A

Active pumping out of antibiotics from the bacterial cell via porins (tetracyclines)

37
Q

Main mechanisms of AMR

A

Natural resistance

Point mutations (SNPs)

Transformation (uptake of DNA from other cells)

Transduction (infection from bacteriophage)

Conjugation (exchange of genetic material)

  • Plasmids (extrachromosomal)
  • Transposons (chromosomal)
38
Q

Antimicrobials in special populations

A
  • Antibiotic allergy
  • Extremes of age – infants and the elderly
  • Impaired drug absorption or excretion
  • Obesity
  • Pregnancy and breastfeeding women
39
Q

Antibiotic allergy types

A

Most adverse drug reactions are not immune mediated

Immune mediated reactions:

• Type 1 (immediate, IgE mediated) resulting in urticaria, angioedema or anaphylaxis (medical emergency)

• Type 2 (cytotoxic) resulting in drug induced haemolysis (uncommon) • Type 3 (immune complexes) resulting in serum sickness like reactions (fever, rash, arthralgia) after several days)

• Type 4 (delayed hypersensitivity) resulting in multiorgan involvement after several weeks (DRESS, SJS/TEN and potentially life threatening)

40
Q

What are the reactions that occured after they had their antibiotics?

A

DRESS syndrome is a delayed type IVb hypersensitivity reaction thought to be mediated by antiviral T cells. 2. It is a severe, idiosyncratic multisystem reaction to a drug, characterised by fever, skin rash, lymphadenopathy, haematological abnormalities and internal organ involvement.

41
Q
A

Most common reported allergy (10-15%) Most are not allergic – check the history

Allergic: more common to have delayed reactions

Allergic: immediate hypersensitivity reactions decrease over time (50% at 5yrs) but avoided in all

Allergic: cross reactivity with cephalosporins

42
Q

What antibiotics are safe to give

What antibiotics re not and what can you get?

A

SAFE • Penicillins • Cephalosporins • Clindamycin • Glycopeptides • Metronidazole

NOT SAFE

  • Carbapenems (manufacturer warning)
  • Macrolides (manufacturer warning)
  • Quinolones (animal skeletal development)
  • Folate antagonists (neural tube defects)
  • Tetracyclines (skeletal development)
  • Aminoglycosides (gentamycin) (auditory/vestibular nerve damage)

Year 3 Lecture Content (33 decks)

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