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YEAR 5: MICRO > 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 4 groups of antibiotics are classified as beta lactams?

A

Penicillins

Cephalosporins

Carbapenems

Monobactams - not used much, recently reintroduced for drug resistance

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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 cell wall synthesis.

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 e.g. inert bacteria in abcess*

Not effective against organism without peptipoglycan cell wall e.g. mycoplasma, chlamydia

Bactericidal

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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 e.g. vancomycin)

*Gram pos stain purple, gram neg stain pink*

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8
Q

gram positive stain

A

deep purple

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9
Q

gram negative stain

A

pink

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10
Q

What bacteria is penicillin active against?

A

Gram pos

Streptococci, clostridia

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

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11
Q

What bacteria is amoxicillin active against?

A

Broad spectrum penicillin: gram pos and many gram neg

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

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12
Q

Which beta lactam antibiotic is effective against pseudomonas?

A

Piperacillin

*Broken down by beta lactamase*

Pseudomonas is important hospital associated pathogen

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13
Q

what beta lactam is stable to beta lactamase

A

Flucloxacillin

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14
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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15
Q

Recall an antibiotic that is associated with C. difficile

A

Ceftriaxone (cephalosporin)

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16
Q

Examples of cephalosporins

A

Cefalexin (1st generation)

Cefuroxime (2nd generation)

Ceftriaxone (3rd generation)

Ceftazidime (3rd generation)

Cefotaxime (3rd generation, paediatric cefotriaxone, anti-pseudomonas)

*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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17
Q

What limits the use of cephalosporins?

A

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

Also non-cover anaerobes

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18
Q

Which beta lactam antibiotics are stable to ESBL organisms?

A

Carbapenems

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

Meropenem, Ertapenem, Imipenem

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19
Q

What is resistant to carbapenems

A

Klebsiella, Actineobacter

Carbapenemases

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20
Q

Recall the key features of beta lactams

A

Relatively non-toxic

Renally excreted so decrease dose if renal impairment

Short half-life

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

Cross allergenic – penicillin has 2% cross reactivity with cephalosporins and carbapenems

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21
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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22
Q

What are glycopeptides particularly useful for?

A

MRSA infection (IV)

C.diff infection (oral vancomycin)

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23
Q

Would you prefer to give beta lactam or glycopeptide

A

would prefer to use beta lactam over glycopeptides

faster activity, less toxic

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24
Q

What is a caution of glycopeptide antibiotics?

A

They are nephrotoxic

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25
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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26
Q

What Abx classes inhibt protein synthesis

A

Aminoglycosides

Tetracyclines

Macrolides

Chloramphenicol

Oxazolidinones (e.g. Linezolid)

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27
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*

No activity against anaerobes

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28
Q

Recall 2 examples of aminoglycoside antibiotics

A

gentamicin

amikacin

Gentamicin + tobramycin - against pseudomonas

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29
Q

What type of bacteria are aminoglycoside antibiotics effective against?

A

Gram neg

Aerobes (no activity against anaerobes)

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30
Q

Recall 2 toxicities of aminoglycosides

A

Ototoxicity

Nephrotoxicity

Must monitor levels

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31
Q

What type of bacteria are macrolides effective against?

A

Gram pos

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32
Q

What are macrolides particularly useful for?

A

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

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33
Q

Recall 2 macrolide antibiotics

A

Azithromycin

Clarithromycin

34
Q

What type of bacteria are tetracylines effective against?

A

They are broad spectrum

good against intracellula pathogens e.g. chlamydiae, rickettsia, mycoplasma)

Bacteriostatic

35
Q

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

A

Tetracyclines

due to deposition in teeth + bone

36
Q

Recall one side effect of tetracycline antibiotics

A

Light-sensitive rash

37
Q

Recall the broad mechanism of action of macrolides

A

Bind to the 50s subunit of ribosomes

38
Q

Recall the broad mechanism of action of tetracyclines

A

Reversibly bind to 30s subunit of ribosomes

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

39
Q

What type of bacteria is chloramphenicol effective against?

A

Many - it is v broad spectrum

40
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*

41
Q

Recall 2 specific bacteria that macrolides are effective against

A

Campylobacter sp

Legionella pneumophila

(macrolides = erythromycin/ azithromycin/ clarithromycin)

42
Q

Recall the broad mechanism of action of chloramphenicol

A

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

43
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

44
Q

Recall two types of bacteria that oxazolidinones are particularly active against

A

Highly active against gram positive organisms - especially MRSA and VRE

Not active against most gram -ve

45
Q

Recall an example of oxazolidinones

A

Linezolid

46
Q

Recall one potential side effect of oxazolidinones

A

Thrombocytopaenia and permanent neurological side effects e.g. optic neuritis if used longer than 4 weeks

FBC monitored weekly on linezolid, only used for 4 weeks

47
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)

48
Q

what are the inhibitors of DNA synthesis

A

fluoroquinolones

49
Q

Recall the broad mechanism of action of fluoroquinolones

A

Act on alpha subunit of DNA gyrase

50
Q

Recall 4 uses of fluoroquinolones

A

UTI

Pneumonia

Atypical pneumonia

Bacterial gastroenteritis

*Broad antibacterial activity against gram negatives*

Lots of side effects + resistance –.> use has dimininshed

51
Q

Most common quinolone side effect

A

achilles tendonitis

Always consider if alternative to quinonlon

52
Q

Recall 2 examples of fluoroquinolone antibiotics

A

Levofloxacin

Moxifloxacin

53
Q

How do nitroimidazoles work?

A

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

54
Q

Give examples of nitromidazole antibiotics

A

Metronidazole

Tinidazole

55
Q

Recall types of organisms that metronidazole is effective against

A

Anaerobes

Protozoa e.g. giardia

56
Q

When should metronidazole be taken?

A

Right after visiting the toilet as it sits in bladder

57
Q

Recall the broad mechanism of action of rifampicin

A

Binds to DNA-dependent RNA polymerase to inhibit RNA synthesis

58
Q

What ABx are the inhibitors of RNA synthesis

A
59
Q

Recall the main use of rifampicin

A

TB treatment

60
Q

Recall one side effect of rifampicin

A

Turns secretions orange

61
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*

Monitor LFTs

62
Q

What are the cell membrane toxin ABx

A

Daptomycin

Colistin

63
Q

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

A

It is active against certain multi-drug resistant bacteria

64
Q

What is daptomycin licensed for the treatment of?

A

MRSA

VRE

65
Q

Recall the 2 classes of antibiotic that inhibit folate synthesis

A

Sulphonamides

Diaminopyrimidines (e.g. trimethoprim)

66
Q

Give an example of a sulphonamide

A

Sulfamethazole

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

67
Q

What is the main use of trimethoprim

A

Uncomplicated UTI

68
Q

Which antibiotic is best for treating pneumocystis jirovecii?

A

Co-trimoxazole

69
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)

70
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)
71
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

72
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* - may not be possible for meningitis due to crossing BBB

73
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*

74
Q

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

A

Staphylococcus

75
Q

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

A

Streptococcus

Strep sounds like ‘stripe’ = chain

76
Q

What gram stain status are enterococci?

A

Positive

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

77
Q

Is streptococci gram pos or neg?

A

Gram pos

78
Q

Is pseudomonas gram pos or gram neg?

A

Gram neg

(Pseudo”moan”as - ‘moan’ = negative)

79
Q

Is neisseria meningitis gram pos or gram neg?

A

Gram neg

(Neisseria starts with N = negative)

80
Q

Is haemophilus gram pos or neg?

A

Gram neg

Ha”emo”philus - emo = negative

81
Q

Is listeria gram pos or neg?

A

Positive

Lister = good man = positive

YEAR 5: MICRO (24 decks)

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