Antimicrobials 1 Flashcards by Jasleen Sambhi (2025)

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 group of 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*

That’s why it’s used as tazocin

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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
- side effects?
- route of metabolisation
- half life
- reactivity with blood brain barrier
- if a person is allergic to penicillins, what does this mean

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

What type of bacteria are macrolides effective against?

Gram pos

26

What are macrolides particularly useful for?

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

27

Recall 2 macrolide antibiotics

AzithromycinClarithromycin

28

What type of bacteria are tetracylines effective against?

They are broad spectrum

29

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

Tetracyclines

30

Recall one side effect of tetracycline antibiotics

Photosensitivity --> Light-sensitive rash (believed to be because tetracycline can absorb UV light and release that energy to skin cells in form of reactive oxygen species)

31

Recall the broad mechanism of action of macrolides

Bind to the 50s subunit of ribosomes

32

Recall the broad mechanism of action of tetracyclines

Bind to 30s subunit of ribosomes\*Bacteriostatic - still useful in certain situations, especially with MRSA\*

33

What type of bacteria is chloramphenicol effective against?

Many - it is v broad spectrum

34

Why is chloramphenicol rarely used?

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

Recall 2 specific bacteria that macrolides are effective against

Campylobacter spLegionella pneumophila(macrolides = erythromycin/ azithromycin/ clarithromycin)

36

Recall the broad mechanism of action of chloramphenicol

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

37

Recall the broad mechanism of action of oxazolidinones

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

38

Recall two types of bacteria that oxazolidinones are particularly active against

Highly active against gram positive organisms - especially MRSA and VRE

39

Recall an example of oxazolidinones

Linezolid

40

Recall one potential side effect of oxazolidinones

Thrombocytopaenia and neurological side effects if used longer than 4 weeks

41

Which antibiotics inhibit protein synthesis by binding to the:30s subunit50s subunit

30s = aminoglycosides, tetracyclines50s = macrolides, chloramphenicol, oxazolidinones (binds to the 23s portion)

42

Recall the broad mechanism of action of fluoroquinolones

Act on alpha subunit of DNA gyrase

43

Recall the uses of fluoroquinolonesWhich bacteria types are susceptible

Complicated UTIMeningococcal chemoprophylaxisPneumoniaAtypical pneumoniaBacterial gastroenteritis\*BROAD SPECTRUM antibacterial activity against gram negatives\*

44

Recall examples of fluoroquinolone antibiotics

LevofloxacinMoxifloxacinCiprofloxacin

45

How do nitroimidazoles work?

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

46

Give examples of nitromidazole antibiotics

MetronidazoleTinidazole

47

Recall types of organisms that metronidazole is effective against

AnaerobesProtozoa

48

When should metronidazole be taken?

Right after visiting the toilet as it sits in bladder

49

Recall the broad mechanism of action of rifampicin

Binds to DNA-dependent RNA polymerase to inhibit RNA synthesis

50

Recall the main use of rifampicin

TB treatment

51

Recall one side effect of rifampicin

Turns secretions orange

52

Recall one condition of rifampicin prescription

Should never be prescribed alone as resistance develops very quickly\*Resistance is caused by a single amino acid change\*

53

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

It is active against certain multi-drug resistant bacteria

54

What is daptomycin licensed for the treatment of?

MRSAVRE

55

Recall the 2 classes of antibiotic that inhibit folate synthesis

SulphonamidesDiaminopyrimidines (e.g. trimethoprim)

56

Give an example of a sulphonamide

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

57

What is the main use of trimethoprim

Uncomplicated UTI

58

Which antibiotic is best for treating pneumocystis jirovecii?

Co-trimoxazole

59

Give 2 examples of cell membrane toxins

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

What are the 4 main mechanisms of resistance

***inactivation, target, accumulation, bypass ***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 prevented3. Reduced accumulation (most important in **gram negs** - either due to enhanced efflux or to reduced uptake)4. Bacteria bypasses antibiotic sensitive step (particularly important for **folate inhibitors** - bacteria can change the enzyme they use)

61

How is MRSA resistant to all beta lactams?

**MRSA survives beta-lactams by using PBP2a (from mecA) – a version of the target that the antibiotics can’t bind to**.mecA gene encodes novel penicillin binding protein (2A) / novel PBP 2aLow affinity for binding beta lactamsSubstitutes for essential functions of high affinity PBPs at otherwise lethal concentrations of antibiotics

62

How does Strep pneumoniae develop beta lactam resistance?

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

How do bacteria become resistant to macrolides?

**erm gene → methylates 23S rRNA → macrolide can’t bind → resistance**Adenine-N6 methyltransferase modifies 23S rRNA -\> reduces binding of MLS antibiotics and results in resistanceEncoded by **erm gene** (erythromycin ribosome methylation)\*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

Which bacteria typically forms "gram pos cocci in clusters"?

Staphylococcus

65

Which bacteria typically forms "gram pos cocci in chains"?

StreptococcusStrep sounds like 'stripe' = chain

66

What gram stain status are enterococci?

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

67

Is streptococci gram pos or neg?

Gram pos

68

Is pseudomonas gram pos or gram neg?

Gram neg(Pseudo"moan"as - 'moan' = negative)

69

Is neisseria meningitis gram pos or gram neg?

Gram neg(Neisseria starts with N = negative)

70

Is haemophilus gram pos or neg?

Gram negHa"emo"philus - emo = negative

71

Is listeria gram pos or neg?

PositiveLister = good man = positive

Antimicrobials 1 Flashcards by Jasleen Sambhi (2025)

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