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PATH FINAL > Micro: Antimicrobials > Flashcards

Micro: Antimicrobials Flashcards

1
Q

3 main selective targets for antibiotics

A
  • Inhibition of cell wall synthesis (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

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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3
Q

What is the broad mechanism of action of beta lactams?

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

(used in sequence depending on resistance)

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5
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. (Bacterialcidal)

They are effective against rapidly dividing bacteria, which are constantly using transpeptidase to form their cell wall - NOT useful in bacteria that is not dividing as the cell wall has already been formed

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6
Q

Which bacteria are beta-lactams ineffective against

A

Ineffective against bacteria that lack a peptidoglycan cell wall (hence not gram pos or gram negative as both have a peptidoglycan cell wall).

Examples of such bacteria are: Chlamydia and Mycoplasma

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7
Q

Common examples of penicillins

A

Penicillin
Amoxicillin
Flucloxacillin
Piperacillin

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8
Q

What bacteria is penicillin mainly active against?

A

Gram +ve (specifically Strep and Clostridia - behind gastroenteritis )

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 +ve and many gram -ve

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10
Q

What is the main indication for Flucloxacillin

A

Skin infections (Staph A)

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11
Q

Main indication for Piperacillin

A

Commonly used in Hospital neutropaenic sepsis as covers pseudomonas (used as Tazocin)

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12
Q

Mechanism of resistance bacteria gain aganist penicillin

A

Beta lactamase (drug inactivation)

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13
Q

Examples of cephalosporins (3)

A

Cefuroxime (2nd generation)

Ceftriaxone (3rd generation)

Ceftazidime (3rd generation)

As cephalosporins progressed from 1st to 3rd generation, they became more effective against gram negative and less effective against gram positive - newer generation does not act against Staph A.

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14
Q

Important features of Cefuroxime

A
  • Stable to many beta lactamases by gram +ve
  • less active against anaerobes - hence used in combination with metronidazole in GI cases
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15
Q

Important features of Ceftriaxone

A
  • Broad spectrum
  • good cover against community acquired meningitis as has good penetration of CNS
  • associated with C. Diff
  • increasingly decreased utility due to ESBL
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16
Q

Important features of Ceftazidime

A
  • Activity against pseudomonas (useful for HAP)
  • Note it is less active against Staph A compared to other 1st and 2nd gen cephalosporins
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17
Q

Mechanism of resistance bacteria gain aganist cephalosporins

A

Extended Spectrum Beta Lactamase (ESBL) - these bacteria are resistant to both penicillins and cephalosporins

drug inactivation

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18
Q

Which beta lactam antibiotics are stable to ESBL organisms?

A

Carbapenems

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19
Q

Examples of Carbapenems (beta lactam)

A

Meropenem
Ertapenem

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20
Q

Main indication of Carbapenem

A

Used for ESBL producing bacteria

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21
Q

Mechanism of resistance bacteria gain aganist carbapenems- list specific bacteria this has been seen on

A

Carbapenamase (especially in Acinetobacter and Klebsiella) - drug inactivation

this has lead to an returned use of Monobactam antibiotics to treat carbapenamase bacteria

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22
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)

Note that clavulanic acid and Tazobactam are only effective at inhibiting group A beta lactamase

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23
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 (becoming less common)

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24
Q

What is the mechanism of action of glycopeptide antibiotics?

A

Inhibition of cell wall synthesis by preventing 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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25
Q

Name 2 glycopeptide antibiotics

A

Vancomycin

Teicoplanin

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26
Q

What type of bacteria are glycopeptides effective against?

A

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

Good for MRSA (IV) and C.Diff (Oral)

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27
Q

What are glycopeptides particularly useful for?

A

MRSA infection (especially in bacteriaemia and endocarditis). This is because MRSA is resistant to all beta lactam antibiotics

Vancomycin specififcally useful for C-Diff

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28
Q

What is a caution of glycopeptide antibiotics?

A

They are nephrotoxic

Hence important to monitor drug level (mainly the trough level - lowest level maintained after initial peak of intake lowers).

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29
Q

List antibiotic classes which inhibit protein synthesis
(TAMCO)

A

Tetracyclines
Aminoglycosides
Macrolides
Chloramphenicol
Oxazolidinones

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30
Q

Recall the broad mechanism of action of aminoglycosides

A

Bind to 30s ribosomal subunit, preventing elongation of polypeptide chain and cause misreading of codons along mRNA

However this does not fully explain their antimicrobial effect

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31
Q

Recall 2 examples of aminoglycoside antibiotics

A

Gentamicin
Amikacin
Tobramycin

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32
Q

What type of bacteria are aminoglycoside antibiotics effective against?

A

Gram -ve
- sepsis
- good cover for pseudomonas

Aerobes
- no activity against anaerobes as oxygen is required for the uptake of the antibiotic into the bacteria

Have synergetic effect with beta lactams and used to treat G+ve endocarditis

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33
Q

What pharmokinetic pattern of activity do aminoglycosides

A

Rapid concentration dependent effect - meaning the high initial peak dose is crucial for its antimicrobial action, and following it they have a post-antibiotic effect where the antimicrobial action is maintained.

This is why many aminoglycosides are given as a one-off high dose.

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34
Q

Recall 2 toxicities of aminoglycosides

A

Ototoxicity

Nephrotoxicity

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35
Q

Mechanism of actions of Macrolides

A

Act on 50s ribosome
Inhibit translocation
Bacteriostatic action (doesn’t kill bacteria it prevents it from dividing)

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36
Q

Examples of 2 macrolide antibiotics

A

Azithromycin

Clarithromycin

37
Q

What type of bacteria are macrolides effective against?

A

Gram +ve
cannot cross polar gram -ve outer membrane

38
Q

Recall 2 specific gram -ve bacteria that macrolides are effective against

A

Campylobacter sp

Legionella pneumophila

(macrolides = erythromycin/ azithromycin/ clarithromycin)

39
Q

What are macrolides particularly useful for?

A

Used if patients have penicillin allergy - especially for mild staph or strep infections

40
Q

Recall the broad mechanism of action of tetracyclines

A

Bind to 30s subunit of ribosomes

Bacteriostatic - not useful for sepsis but still useful in certain situations, especially with MRSA

41
Q

Example of a Tetracycline

A

Doxycyline

42
Q

What type of bacteria are tetracylines effective against?

A

Broad spectrum (good cover for MRSA) + some intracellular bacteria (e.g. Chlamydia)
Used for lyme disease

43
Q

Who is contra-indicated to recieve tetracycline

A

Children under 12 or pregnant women

44
Q

Recall one side effect of tetracycline antibiotics

A

Light-sensitive rash

45
Q

Mechanism of action of Chloramphenicol

A

Acts on 50s ribosome inhibiting formation of peptide bonds in translocation

Bacteriostatic

46
Q

What type of bacteria is chloramphenicol effective against?

A

Broad spectrum HOWEVER is only used if beta lactams cannot be utilised (e.g. meningitis in pts with severe allergy to beta lactams

47
Q

Why is chloramphenicol rarely used?

A

Due to severe side effects:
- Aplastic anaemia
- Grey baby syndrome in neonates due to inability to metabolise drug

48
Q

What is the sole indication to use chloramphenicol

A

Bacterial conjunctivitis

49
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

50
Q

Recall an example of oxazolidinones

A

Linezolid

51
Q

Recall two types of bacteria that oxazolidinones are particularly active against

A

Highly active against gram positive organisms - especially MRSA and VRE

52
Q

Recall one potential side effect of oxazolidinones

A

Bone marrow suppression (commonyl resulting in thrombocytopaenia)

Irreversible optic neuritis if used longer than 4 weeks

53
Q

Antibiotic class that inhibits DNA synthesis

A

Fluoroquinolones
Nitroimidazole

54
Q

Recall the broad mechanism of action of fluoroquinolones

A

Act on alpha subunit of DNA gyrase
Bacterialcidal

55
Q

Recall 2 examples of fluoroquinolone antibiotics

A

Ciprofolaxin

Levofloxacin

56
Q

Recall 4 uses of fluoroquinolones

A

Broad antibacterial activity especially against gram negatives

  • UTI
  • Atypical pneumonia (particularly pseudomonas)
  • Bacterial gastroenteritis
57
Q

Side effects of Fluoroquinolones

A
  • Lower seizure threshold (not to be used in epileptic patients)
  • Tendinitis
58
Q

How do nitroimidazoles work?

A

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

Bacterialcidal

59
Q

Give examples of nitromidazole antibiotics

A

Metronidazole

Tinidazole

Nitrofurantoin is a related component of nitromidazole antibiotics

60
Q

Recall types of organisms that metronidazole is effective against

A

Anaerobes

Protozoa (giardia, amoeba)

61
Q

Commonly in which cases do we use Nitroimidazole (specifically Metronidazole)

A

Commmonly used in combination with Cephalosporin for GI tract cases to allow cover for anaerobic bacteria (which is not achieved with cephalosporin alone)

62
Q

Indication for nitrofurantoin and when should it be taken?

A

Simple UTIs
Right after visiting the toilet as it sits in bladder

63
Q

Recall the broad mechanism of action of Rifamycin (rifampicin)

A

Binds to DNA-dependent RNA polymerase to inhibit RNA synthesis

64
Q

Recall the main use of rifampicin

A

TB treatment - always used in combination as resistance develops quickly as it requires solely one amino acid change

65
Q

Recall one side effect of rifampicin

A

Turns secretions orange (red urine)

66
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)

67
Q

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

A

It is active against certain multi-drug resistant bacteria

68
Q

What is daptomycin (type of colistin) licensed for the treatment of?

A

MRSA

VRE

69
Q

Recall the 2 classes of antibiotic that inhibit folate synthesis

A

Sulphonamides

Diaminopyrimidines (e.g. trimethoprim)

70
Q

Give an example of a sulphonamide

A

Sulfamethoxazole

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

71
Q

What is the main use of trimethoprim

A

Uncomplicated UTI

72
Q

Common indication of Sulphamethoxazole

A

pneumocystis jirovecii (PCP)

As co-trimoxazole

73
Q

What are the 4 main mechanisms of resistance

A
  1. Inactivation of the antibiotic (eg beta lactamases)
  2. Modification of drug’s target target - so antibiotic no longer binds (e.g. MRSA, Strep pneumoniae)
  3. Reduced accumulation of drug by either impaired uptake or enhanced efflux (e.g. common in gram -ves)
  4. Bypass antibiotic-sensitive step in pathway

Note that often resistance occurs from more than 1 mechanism happening

74
Q

How is MRSA resistant to all beta lactams?

A

It is resistant by modifying the drug’s target in the microbe.

MRSA has mecA gene which encodes novel penicillin binding protein (2A) / novel PBP 2a. This has low affinity for binding beta lactams

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

75
Q

How does Strep pneumoniae develop beta lactam resistance?

A

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

As it is a stepwise acquisiton resistance, depending on level of mutations, resistance can range from lower level to high level. In the UK lower level resistance is commonest. This can be overcome by increasing dose of penicillin used - hence why for CAP abx regimes we begin with a high dose of amoxicillin. This is not the case in meningitis - because of the already existing difficulty in abx to cross the BBB, the concentration of abx is never enough to overcome lower level resistance. In cases of strep. p. meningitis you’d add vancomycin if any concern about resistance - note that here co-amoxiclav would not help as there beta lactamase is NOT the source of resistance

76
Q

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

A

Staphylococcus

77
Q

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

A

Streptococcus

Strep sounds like ‘stripe’ = chain

78
Q

What gram stain status are enterococci?

A

Positive

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

79
Q

Is streptococci gram pos or neg?

A

Gram pos

80
Q

Is pseudomonas gram pos or gram neg?

A

Gram neg

(Pseudo”moan”as - ‘moan’ = negative)

81
Q

Is neisseria meningitis gram pos or gram neg?

A

Gram neg

(Neisseria starts with N = negative)

82
Q

Is haemophilus gram pos or neg?

A

Gram neg

Ha”emo”philus - emo = negative

83
Q

Is listeria gram pos or neg?

A

Positive

Lister = good man = positive

84
Q

Define the MIC

A

The minimum amount of abx required to inhibit bacterial growth (calculated in lab). It shows how susceptible an organism is to an antibiotic.

Can compare to the breakpoint to see if clinically indicated. if breakpoint is lower than MIC then yes, if not then minimum concentration is too high and should not be given.

85
Q

Outline the different pattern of activity antibiotics may exhibit

A

Type 1 = Concentration-dependent killing and prolonged persistent effects
- You are trying to maximise the peak concentration of antibiotic above the MIC value. - Goal of therapy = maximising initial concentration of abx given
- In these antibiotics they are often given as one-off high doses
- Examples = Aminoglycosides, Fluoroquinolones, Daptomycin

Type 2 = Time-Dependent killing and minimal persistent effects
- You are trying to maximise the amount of time in which abx concentration is above the MIC
- Goal of therapy = maximise duration of exposure to concentration > MIC
- These antibiotics are often given as infusions or dose regimens require being taken more than once a day
- Examples = Beta lactams, Erythromycin

Type 3 = Time-dependent killing and moderate/prolonged persistent effects
- You are trying to maximise the concentration of the drug, and also keep it as long as possible in maximised concentration above the MIC
- A junction per say of the two above
- Examples = Azithromycin, Tetracycline, Oxalidinones

86
Q

Specific antibiotic recommendation for:
N. Meningitidis
Acute Osteomyelitis (adults)
Bacterial endocarditis
Group A Strep
Simple Cystitis

A

N. Meningitidis –> 7 days
Acute Osteomyelitis (adults) –> 6 weeks
Bacterial endocarditis –> 4-6 weeks
Group A Strep –> 10 days (7d in new NICE guide)
Simple Cystitis –> 3 days (if pregnant, men, catheter = 7 days)

87
Q

Common antibiotic regiment used for CAP

A

Beta Lactam + Macrolide
(beta lactam covers against the common pathogens while macrolides covers against the atypicals which lack a cell wall and therefore bypass beta lactam action)

88
Q

1st line abx for pseudomonas

A

aminoglycosides (gentamicin)

89
Q

Outline the resistance mechanism seen in each circumstance below:
1. ESBL E. coli resistance to ceftriaxone
1. Resistance to macrolides
1. Resistance to trimethoprim and sulphonamides
1. MRSA resistance to flucloxacillin
1. Resistance to Rifampicin

A
  1. ESBL E. coli resistance to ceftriaxone - Enzymatic inactivation of the antibiotic
  2. Resistance to macrolides - Alteration of the target
  3. Resistance to trimethoprim and sulphonamides - Bypass of antibiotic-sensitive step
  4. MRSA resistance to flucloxacillin - Alteration of the target
  5. Resistance to Rifampicin - Alteration of the target

PATH FINAL (36 decks)

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