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Important Path > MI: Antimicrobials 1 > Flashcards

MI: Antimicrobials 1 Flashcards

1
Q

Examples of selective targets for antibiotics

A

Peptidoglycan layer of cell wall

Inhibition of bacterial protein synthesis

Inhibition of DNA gyrase and other prokaryote specific enzymes

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2
Q

What is the broad mechanism of action of beta lactams?

A

Inhibition of cell wall synthesis

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3
Q

What is the broad mechanism of action of glycopeptide antibiotics?

A

Inhibition of cell wall synthesis

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4
Q

What 3 groups of antibiotics are classified as beta lactams?

A

Penicillins

Cephalosporins

Carbapenems

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5
Q

Name 2 glycopeptide antibiotics

A

Vancomycin

Teicoplanin

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6
Q

Describe the mechanism of action of beta lactams

A

Inhibits transpeptidase, which is an enzyme that forms cross links during the formation of the cell wall.

The resulting cell wall is therefore weak, and so the bacteria lyse because of osmotic pressure.

*They are effective against rapidly dividing bacteria - not useful if the cell wall has already been formed*

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7
Q

How does the cell wall of gram pos and gram neg bacteria differ?

A

Gram pos: thick peptidoglycan layer, no outer membrane

Gram neg: thin peptidoglycan layer, has an outer membrane (some antibiotics can’t get through this)

*Gram pos stain purple, gram neg stain pink*

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8
Q

What bacteria is penicillin active against?

A

Gram pos

Not effective against organisms with no peptidoglycan cell wall e.g. mycoplasma and chlamydia

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9
Q

What bacteria is amoxicillin active against?

A

Broad spectrum: gram pos and many gram neg

*Broken down by beta lactamase produced by S. aureus and other microorganisms*

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10
Q

Which beta lactam antibiotic is effective against pseudomonas?

A

Piperacillin

*Broken down by beta lactamase*

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11
Q

How can beta lactam resistance be overcome?

A

Include a beta lactamase inhibitor

Eg. Clavulanic acid + amoxicllin (in co-amoxiclav aka augmentin)

Eg. Tazobactam + piperacillin (in tazocin)

Alternatively, create antibiotics that are stable to beta lactamase eg. flucloxacillin

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12
Q

Recall an antibiotic that is associated with C. difficile

A

Ceftriaxone (cephalosporin)

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13
Q

Examples of cephalosporins

A

Cefalexin (1st generation)

Cefuroxime (2nd generation)

Ceftriaxone (3rd generation)

Ceftazidime (3rd generation)

Cefotaxime (3rd generation, paediatric cefotriaxone)

*As cephalosporins progressed from 1st to 3rd generation, they became more effective against gram negative and less effective against gram positive*

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14
Q

What limits the use of cephalosporins?

A

Extended spectrum beta lactamase (ESBL) producing organisms are resistant to cephalosporins

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15
Q

Which beta lactam antibiotics are stable to ESBL organisms?

A

Carbapenems

*However, carbapenemase enzyme producing organisms (acinetobacter and klebsiella) are becoming more prevalent*

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16
Q

Recall the key features of beta lactams

A

Relatively non-toxic

Renally excreted so decrease dose if renal impairment

Short T1/2 (many are type 2/time-dependent drugs so aim to maximise the time where concentration > MIC)

Will not cross intact BBB (but can cross in meningitis)

Cross allergenic – penicillin has 10% cross reactivity with cephalosporins and carbapenems

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17
Q

What type of bacteria are glycopeptides effective against?

A

Gram pos only - they are large molecules so can’t penetrate gram neg cell wall

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18
Q

What are glycopeptides particularly useful for?

A

MRSA infection

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19
Q

What is a caution of glycopeptide antibiotics?

A

They are nephrotoxic

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20
Q

Recall the broad mechanism of action of glycopeptide antibiotics

A

Prevent peptide cross links in cell wall

They bind to the amino acid chains at the end of peptidoglycan precursors, to prevent glycosidic bond formation. They prevent transpeptidase activity without directly binding to the enzyme.

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21
Q

Recall the broad mechanism of action of aminoglycosides

A

Bind to 30s ribosomal subunit, preventing elongation of polypeptide chain

*This doesn’t explain their rapid bactericidal activity - full mechanism is unknown*

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22
Q

Recall 2 examples of aminoglycoside antibiotics

A

gentamicin

amikacin

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23
Q

What type of bacteria are aminoglycoside antibiotics effective against?

A

Gram neg

Aerobes (no activity against anaerobes)

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24
Q

Recall 2 toxicities of aminoglycosides

A

Ototoxicity

Nephrotoxicity

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25
Q

What type of bacteria are macrolides effective against?

A

Gram pos

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26
Q

What are macrolides particularly useful for?

A

Mild staph or strep infections in patients who are allergic to penicillin

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27
Q

Recall 2 macrolide antibiotics

A

Azithromycin

Clarithromycin

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28
Q

What type of bacteria are tetracylines effective against?

A

They are broad spectrum

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29
Q

Recall a class of antibiotic you should never give to children or pregnant women

A

Tetracyclines

30
Q

Recall one side effect of tetracycline antibiotics

A

Light-sensitive rash

31
Q

Recall the broad mechanism of action of macrolides

A

Bind to the 50s subunit of ribosomes

32
Q

Recall the broad mechanism of action of tetracyclines

A

Bind to 30s subunit of ribosomes

*Bacteriostatic - still useful in certain situations, especially with MRSA*

33
Q

What type of bacteria is chloramphenicol effective against?

A

Many - it is v broad spectrum

34
Q

Why is chloramphenicol rarely used?

A

Risk of aplastic anaemia and grey baby syndrome in neonates due to inability to metabolise drug

*Still useful for meningitis when patients have penicillin anaphylaxis*

35
Q

Recall 2 specific bacteria that macrolides are effective against

A

Campylobacter sp

Legionella pneumophila

(macrolides = erythromycin/ azithromycin/ clarithromycin)

36
Q

Recall the broad mechanism of action of chloramphenicol

A

Binds to 50s subunit of ribosomes - inhibits formation of peptide bonds during translation

37
Q

Recall the broad mechanism of action of oxazolidinones

A

Binds to the 23s portion of the 50s ribosome subunit to prevent 70s subunit formation

38
Q

Recall two types of bacteria that oxazolidinones are particularly active against

A

Highly active against gram positive organisms - especially MRSA and VRE

39
Q

Recall an example of oxazolidinones

A

Linezolid

40
Q

Recall one potential side effect of oxazolidinones

A

Thrombocytopaenia and neurological side effects if used longer than 4 weeks

41
Q

Which antibiotics inhibit protein synthesis by binding to the:

30s subunit

50s subunit

A

30s = aminoglycosides, tetracyclines

50s = macrolides, chloramphenicol, oxazolidinones (binds to the 23s portion)

42
Q

Recall the broad mechanism of action of fluoroquinolones

A

Act on alpha subunit of DNA gyrase

43
Q

Recall 4 uses of fluoroquinolones

A

UTI

Pneumonia

Atypical pneumonia

Bacterial gastroenteritis

*Broad antibacterial activity against gram negatives*

44
Q

Recall 2 examples of fluoroquinolone antibiotics

A

Levofloxacin

Moxifloxacin

45
Q

How do nitroimidazoles work?

A

Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage

46
Q

Give examples of nitromidazole antibiotics

A

Metronidazole

Tinidazole

47
Q

Recall types of organisms that metronidazole is effective against

A

Anaerobes

Protozoa

48
Q

When should metronidazole be taken?

A

Right after visiting the toilet as it sits in bladder

49
Q

Recall the broad mechanism of action of rifampicin

A

Binds to DNA-dependent RNA polymerase to inhibit RNA synthesis

50
Q

Recall the main use of rifampicin

A

TB treatment

51
Q

Recall one side effect of rifampicin

A

Turns secretions orange

52
Q

Recall one condition of rifampicin prescription

A

Should never be prescribed alone as resistance develops very quickly

*Resistance is caused by a single amino acid change*

53
Q

Colistin is very toxic. Why is it coming back into use?

A

It is active against certain multi-drug resistant bacteria

54
Q

What is daptomycin licensed for the treatment of?

A

MRSA

VRE

55
Q

Recall the 2 classes of antibiotic that inhibit folate synthesis

A

Sulphonamides

Diaminopyrimidines (e.g. trimethoprim)

56
Q

Give an example of a sulphonamide

A

Sulfamethazole

*Sulfonamides aren’t used on their own - should be in combination with trimethoprim (co-trimoxazole)

57
Q

What is the main use of trimethoprim

A

Uncomplicated UTI

58
Q

Which antibiotic is best for treating pneumocystis jirovecii?

A

Co-trimoxazole

59
Q

Give 2 examples of cell membrane toxins

A

Daptomycin (lipopeptide with limited activity to gram positives - potential alternative to linezolid and synercid for MRSA and VRE infections)

Colistin (old antibiotic which is very nephrotoxic but it is active against gram negative organisms like pseudomonas)

60
Q

What are the 4 main mechanisms of resistance

A
  1. Inactivation of the antibiotic (eg beta lactamases)
  2. Altered target - so antibiotic no longer binds
  • E.g. penicillin resistant pneumococci or MRSA where bacteria change the penicillin-binding protein
  • E.g. protein-synthesis inhibitors where the binding of the ribosome subunit is prevented
  1. Reduced accumulation (most important in gram negs - either due to enhanced efflux or to reduced uptake)
  2. Bacteria bypasses antibiotic sensitive step (particularly important for folate inhibitors - bacteria can change the enzyme they use)
61
Q

How is MRSA resistant to all beta lactams?

A

mecA gene encodes novel penicillin binding protein (2A) / novel PBP 2a

Low affinity for binding beta lactams

Substitutes for essential functions of high affinity PBPs at otherwise lethal concentrations of antibiotics

62
Q

How does Strep pneumoniae develop beta lactam resistance?

A

Penicillin resistance is the result of acquisition of stepwise mutations in PBP genes

*Lower level resistance can be overcome by increasing dose of penicillin used*

63
Q

How do bacteria become resistant to macrolides?

A

Adenine-N6 methyltransferase modifies 23S rRNA -> reduces binding of MLS antibiotics and results in resistance

Encoded by erm (erythromycin ribosome methylation) genes.

*If bacteria is resistant to erythromycin in this manner but still sensitive to clindamycin, only use clindamycin with caution - sometimes the in-vitro tests aren’t reliable*

64
Q

Which bacteria typically forms “gram pos cocci in clusters”?

A

Staphylococcus

65
Q

Which bacteria typically forms “gram pos cocci in chains”?

A

Streptococcus

Strep sounds like ‘stripe’ = chain

66
Q

What gram stain status are enterococci?

A

Positive

(“Enter-o-coccus” = like letting someone in, positive thing to do)

67
Q

Is streptococci gram pos or neg?

A

Gram pos

68
Q

Is pseudomonas gram pos or gram neg?

A

Gram neg

(Pseudo”moan”as - ‘moan’ = negative)

69
Q

Is neisseria meningitis gram pos or gram neg?

A

Gram neg

(Neisseria starts with N = negative)

70
Q

Is haemophilus gram pos or neg?

A

Gram neg

Ha”emo”philus - emo = negative

71
Q

Is listeria gram pos or neg?

A

Positive

Lister = good man = positive

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