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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 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 resistance due to beta lactamase 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

antibiotics associated with C. difficile

A

cephalosporins
clindamycin
co-amoxiclav
quinolones

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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 low dose if renal impairment

Short half-life

Will not cross intact BBB (but can cross in meningitis as the inflammation makes the tight junctions leaky)

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 and ototoxic

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25
Recall the broad mechanism of action of glycopeptide antibiotics
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*.
26
What Abx classes inhibt protein synthesis
Aminoglycosides Tetracyclines Macrolides Chloramphenicol Clindamycin Oxazolidinones (e.g. Linezolid)
27
Recall the broad mechanism of action of aminoglycosides
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
28
Recall 2 examples of aminoglycoside antibiotics
amikacin gentamicin **A**mino**G**Lycosides | Gentamicin + tobramycin - against pseudomonas
29
What type of bacteria are aminoglycoside antibiotics effective against?
Gram neg Aerobes (no activity against anaerobes)
30
Recall 2 toxicities of aminoglycosides
Ototoxicity Nephrotoxicity | Must monitor levels
31
What type of bacteria are macrolides effective against?
Gram pos
32
What are macrolides particularly useful for?
Mild staph or strep infections in patients who are allergic to penicillin
33
Recall 2 macrolide antibiotics
Azithromycin Clarithromycin
34
What type of bacteria are tetracylines effective against?
They are broad spectrum good against intracellula pathogens e.g. chlamydiae, rickettsia, mycoplasma) | Bacteriostatic
35
Recall a class of antibiotic you should never give to children or pregnant women
Tetracyclines | due to deposition in teeth + bone
36
Recall one side effect of tetracycline antibiotics
Light-sensitive rash
37
Recall the broad mechanism of action of macrolides
Bind to the 50s subunit of ribosomes
38
Recall the broad mechanism of action of tetracyclines
Reversibly bind to 30s subunit of ribosomes \*Bacteriostatic - still useful in certain situations, especially with MRSA\*
39
What type of bacteria is chloramphenicol effective against?
Many - it is v broad spectrum
40
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\*
41
Recall 2 specific bacteria that macrolides are effective against
Campylobacter sp Legionella pneumophila (macrolides = erythromycin/ azithromycin/ clarithromycin)
42
Recall the broad mechanism of action of chloramphenicol
Binds to 50s subunit of ribosomes - inhibits formation of peptide bonds during translation
43
Recall the broad mechanism of action of oxazolidinones
Binds to the 23s portion of the 50s ribosome subunit to prevent 70s subunit formation
44
Recall two types of bacteria that oxazolidinones are particularly active against
Highly active against gram positive organisms - especially MRSA and VRE e.g. Linezolid | Not active against most gram -ve
45
Recall an example of oxazolidinones
Linezolid
46
Recall one potential side effect of oxazolidinones
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
Which antibiotics inhibit protein synthesis by binding to the: 30s subunit 50s subunit
30s = aminoglycosides, tetracyclines 50s = macrolides, chloramphenicol, oxazolidinones (binds to the 23s portion)
48
what are the inhibitors of DNA synthesis
fluoroquinolones metronidazole, niturofuarantoin
49
Recall the broad mechanism of action of fluoroquinolones
inhibit DNA gyrase by binding to alpha subunit
50
Recall 4 uses of fluoroquinolones
UTI Pneumonia Atypical pneumonia Bacterial gastroenteritis \*Broad antibacterial activity against gram negatives\* | Lots of side effects + resistance --.> use has dimininshed
51
Most common quinolone side effect
achilles tendonitis | Always consider if alternative to quinonlon
52
Recall 2 examples of fluoroquinolone antibiotics
Levofloxacin Ciprofloxacin Moxifloxacin
53
How do nitroimidazoles work?
Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage | metronidazole
54
Give examples of nitromidazole antibiotics
Metronidazole Tinidazole
55
Recall types of organisms that metronidazole is effective against
Anaerobes Protozoa e.g. giardia
56
When should metronidazole be taken?
Right after visiting the toilet as it sits in bladder
57
Recall the broad mechanism of action of rifampicin
Binds to DNA-dependent RNA polymerase to inhibit RNA synthesis
58
What ABx are the inhibitors of RNA synthesis
Rifamycins: Rifampicin Rifaximin
59
Recall the main use of rifampicin
TB treatment
60
Recall one side effect of rifampicin
Turns secretions orange
61
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\* | Monitor LFTs
62
What are the cell membrane toxin ABx
Daptomycin Colistin
63
Colistin is very toxic. Why is it coming back into use?
It is active against certain multi-drug resistant bacteria
64
What is daptomycin licensed for the treatment of?
MRSA VRE
65
Recall the 2 classes of antibiotic that inhibit folate synthesis
Sulphonamides Diaminopyrimidines (e.g. trimethoprim)
66
Give an example of a sulphonamide
Sulfamethazole \*Sulfonamides aren't used on their own - should be in combination with trimethoprim (co-trimoxazole)
67
What is the main use of trimethoprim
Uncomplicated UTI
68
Which antibiotic is best for treating pneumocystis jirovecii?
Co-trimoxazole
69
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)
70
What are the 4 main mechanisms of resistance
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 3. 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)
71
How is MRSA resistant to all beta lactams?
beta lactams normally bind to PBP --> prevents formation of crosslinks in peptidoglycan cell wall mecA gene encodes novel penicillin binding protein (2A) = PBP 2a Beta lactams (even at high concentrations) cannot bind to PBP 2a --> cross links form
72
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\* - may not be possible for meningitis due to crossing BBB
73
How do bacteria become resistant to macrolides?
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
Which bacteria typically forms "gram pos cocci in clusters"?
Staphylococcus
75
Which bacteria typically forms "gram pos cocci in chains"?
Streptococcus Strep sounds like 'stripe' = chain
76
What gram stain status are enterococci?
Positive ("Enter-o-coccus" = like letting someone in, positive thing to do)
77
Is streptococci gram pos or neg?
Gram pos
78
Is pseudomonas gram pos or gram neg?
Gram neg (Pseudo"moan"as - 'moan' = negative)
79
Is neisseria meningitis gram pos or gram neg?
Gram neg (Neisseria starts with N = negative)
80
Is haemophilus gram pos or neg?
Gram neg Ha"emo"philus - emo = negative
81
Is listeria gram pos or neg?
Positive Lister = good man = positive

YEAR 5: MICRO (24 decks)

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