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Antibiotics Flashcards

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1
Q

What determines the antimicrobial spectrum of penicillins?

A

Side chains attached to the B-lactam ring

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2
Q

Bacterial strategies of resistance against penicilins

A

B-lactamase to break B-lactam ring
Reduce bacterial permeability to limit intracellular concentration
Increase extrusion of penicillin

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3
Q

What would be used in addition to penicillin in severe pneumonia?

A

Macrolide

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4
Q

Contraindications of penicillins

A
  • Allergy to B-lactam antibiotics
  • Renal impairment
  • Those at risk of C.diff (amoxicillin kills gut flora)
  • Prior flucloxacillin-related hepatotoxicity (flucloxacillin)
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5
Q

How many days does a penicillin skin rash take to present after first exposure?

A

7-10 days

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6
Q

What immunoglobulin mediates an immediate anaphylactic reaction?

A

IgE

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7
Q

How often do penicillins need to be administered?

A

4-6 hourly due to short plasma half-life of 30-60mins

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8
Q

ROA for benzylpenicillin

A

IV or IM - GI absorption is prevented by hydrolysis by gastric acid
Therefore prescribed for the treatment of severe infections usually at high dose

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9
Q

ROA for penicillin V

A

Oral - less severe infections

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10
Q

What would you use to treat a young person with a sore throat of unknown cause?

A

Penicillin V - NOT AMOXICILLIN due to rash associated with amoxicillin & EBV

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11
Q

Penicillin V is mainly used to treat 3 conditions

A

Strep throat
Otitis media
Cellulitis

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12
Q

Penicillin V is active against Gram…

A

Positive bacteria - streptococcus pyogenes (i.e. group A streptococcus) - skin flora

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13
Q

Co-amoxiclav is active against

A

Gram-positive (like other penicillins) - Strep pneumoniae
Gram-negative (addition of amino group to the B-lactam side chain) - Haem influenzae
B-lactamase-producing bacteria (addition of clavulanic acid) - Staph aureus, Gram-negative anaerobes

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14
Q

Empirical treatment of pneumonia

A

Amoxicillin - covers Gram-positive (Strep pneumoniae) and Gram-negative (Haem influenzae)

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15
Q

UTIs are most commonly caused by

A

E. coli (treat with amoxicillin, trimethoprim or nitrofurantoin)

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16
Q

What is the interaction between penicillins and methotrexate?

A

Penicillins reduce renal excretion of methotrexate, increasing the risk of toxicity

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17
Q

What is the interaction between penicillins & warfarin?

A

Broad spectrum penicillins (e.g. amoxicillin) kill normal gut flora that synthesises vitamin K, and therefore enhance the anticoagulant effect of warfarin

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18
Q

Dose & ROA of amoxicillin for severe infections

A

1g 8-hourly IV

IV to oral switch after 48hrs if clinically indicated

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19
Q

Dose & ROA of amoxicillin for mild-to-moderate infection

A

250-500mg 8-hourly oral

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20
Q

How is the prescription of co-amoxiclav written?

A

e.g. 500/125

500mg amoxicillin + 125mg clavulanic acid

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21
Q

For piperacillin, what has the slide chain of broad-spectrum penicillins been converted to? Why is this beneficial?

A

It has been converted to a form of urea. This improves affinity to penicillin-binding proteins, thus increasing the spectrum to include Pseudomonas aeruginosa

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22
Q

What is the benefit of tazobactam?

A

B-lactamase inhibitor, so is active against B-lactamase-producing bacteria, e.g. Staph aureus, Gram-negative anaerobes

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23
Q

Is Haemophilus influenzae Gram-positive or Gram-negative?

A

Negative

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24
Q

Type of infections where antipseudomonal penicillins are used (e.g. Tazocin)

A

Severe infections, particularly where there is a broad spectrum of potential pathogens (including Pseudomonas aeruginosa), antibiotic resistance is likely (e.g. hospital-acquired infection) or if patients are immunocompromised

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25
Dose & ROA for Tazocin
4g piperacillin + 500mg tazobactam (4.5g) | IV infusion every 6-8hrs - 5-14 days with no oral switch possible
26
What is flucloxacillin active against?
B-lactamase-producing staphylococci because it has an acyl side chain that protects the B-lactam ring from B-lactamases
27
How is MRSA resistant against flucloxacillin?
Resists the actions of flucloxacillin by reducing penicillin-binding activity
28
How are penicillins excreted?
Rapid renal excretion means that the plasma half-life is short. Therefore need to be administered 4-6hourly
29
Side effects of penicillins
- Minor GI upset (common) - CNS toxicity (convulsion & coma) can occur with high doses + when renal impairment delays excretion - Antibiotic associated colitis, i.e. C. difficile (broad spectrum) - Liver toxicity (rare but serious)
30
ROA for flucloxacillin
Severe infections/systemically unwell - IV injection or infusion (1-2g) Cellulitis - oral (250-500mg)
31
What is the antimicrobial effect of carbapenems & cephalosporins due to?
B-lactam ring
32
Are penicillins or cephalosporins & carbapenems more resistant to B-lactamases?
Cephalosporins - B-lactam ring is fused with dihydrothiazine ring Carbapenems - B-lactam ring fused with unique hydroxyethyl side chain
33
Generations of cephalosporins 1-5 have increasing activity against Gram-
Negative
34
When are carbapenems & cephalosporins used?
Severe complicated infections - due to broad-spectrum | Antibiotic-resistant organisms
35
Contraindications of carbapenems & cephalosporins
Allergy to penicillin, carbapenems or cephalosporins Risk of C. difficile Epilepsy (carbapenems) Renal impairment
36
Side effects of carbapenems & cephalosporins
GI upset Antibiotic associated colitis (C. diff) due to broad spectrum Hypersensitivity similar to penicillins CNS toxicity & seizures
37
Which antibiotics enhance the anticoagulant effect of warfarin & why?
Broad-spectrum penicillins, carbapenems & cephalosporins, trimethoprim, tetracyclines. Kills normal gut flora which synthesises vitamin K
38
Is Streptococcus pneumoniae Gram-positive or Gram-negative?
Positive
39
Interactions of cephalosporins (2)
Warfarin - potentiates anti-coagulant effect | Aminoglycosides - increase nephrotoxicity
40
ROA of cephalosporins
IV for severe infections (e.g. cefotaxime 2g for meningitis) Oral - only some available orally Bolus infusion or injection IM
41
ROA of carbapenems
Only available for IV administration (injection or infusion)
42
How does trimethoprim work?
Bacteriostatic: inhibits bacterial folate synthesis, which prevents DNA synthesis
43
What is the spectrum of activity of trimethoprim?
Broad spectrum of activity against Gram-positive & Gram-negative bacteria, particularly enterobacteria, e.g. E. coli
44
Why is the clinical utility of trimethoprim reduced?
Widespread bacterial resistance
45
Indication for co-trimoxazole (Septrin)
Pneumocystis pneumonia (opportunistic lung infection) in people with immunosuppression
46
Which drugs are contraindicated in pregnancy?
1. Trimethoprim (folate antagonism is associated with increased risk of foetal abnormalities in the first trimester) 2. Nitrofurantoin (towards term) 3. Tetracyclines
47
Contra-indications of trimethoprim
``` Pregnancy (first trimester) Folate deficiency Renal impairment (dose reduction as unchanged in the urine) ```
48
Side effects of trimethoprim
Most common = GI upset (nausea, vomiting, sore mouth) Skin rash Severe hypersensitivity reactions Impaired haematopoeisis (megaloblastic anaemia, leucopenia, thrombocytopenia) - folate antagonist so monitor FBC if used long-term Hyperkalaemia
49
Trimethoprim interactions (3)
1. Potassium-elevating drugs - ARBs, ACEi 2. Folate antagonists - methotrexate, phenytoin 3. Enhances warfarin effect
50
Elimination of trimethoprim
Mostly excreted unchanged into the urine
51
Why is trimethoprim less effective in people with renal impairment?
It competes with creatinine for secretion into the renal tubules (see a reversible rise in serum creatinine in healthy individuals without renal impairment)
52
What causes bacterial cell death with nitrofurantoin?
Its active metabolite, which is metabolised by nitrofuran reductase
53
What is nitrofurantoin active against?
Gram-positive (Staph saprophyticus) and Gram-negative (E.coli) organisms that commonly cause UTIs
54
What makes certain bacteria resistant to nitrofurantoin?
Those with reduced nitrofuran reductase activity
55
Why is nitrofurantoin unsuitable for pyelonephritis or other complicated UTIs?
Tissue concentrations of nitrofurantoin are very low - reaches therapeutic concentrations in urine through renal excretion
56
Why should nitrofurantoin not be given to babies (3months)?
Haemolytic anaemia - Immature RBCs are unable to mop up nitrofurantoin-stimulated superoxides, which damage RBCs
57
Usual treatment duration for trimethoprim or nitrofurantoin
3-7 days - infection severity determines duration
58
Something harmless to warn patients about with nitrofurantoin
Urine may turn dark yellow or brown
59
Which 3 types of antibiotics bind to ribosomal subunits 30S and 50S?
30S - tetracyclines (e..g doxycycine), aminoglycosides (e.g. gentamicin) 50S - macrolides (clarithromycin, erythromycin, etc.)
60
Purpose of binding to 30S
Inhibits protein synthesis by preventing binding of tRNA to mRNA, which prevents addition of new amino acids to the growing polypeptide chain
61
Indications for tetracyclines
Acne vulgaris LRTIs - infective exacerbations of COPD, pneumonia, atypical pneumonia Chlamydia
62
Side effects of doxycycline
Most common = GI upset Hypersensitivity reactions Oesophageal irritation, ulceration, dysphagia Photosensitivity & sun burn
63
Absorption of tetracyclines is prevented if given within 2 hours of...
Calcium (so don't take with milk), Antacids or Iron | Because it binds to divalent cations
64
Why does the mechanism of action of aminoglycosides mean they are active against Gram-negative aerobes, staphylococci & mycobacteria (e.g. TB), and NOT against streptococci & anaerobic bacteria
Enter bacterial cells via an oxygen-dependent transport system, which streptococci & anaerobic bacteria do not have
65
Is Pseudomonas aeruginosa Gram-positive or Gram-negative?
Gram-negative aerobe
66
Indications for gentamicin
Severe infections caused by Gram-negative aerobes: | Severe sepsis, Pyelonephritis, Intra-abdominal sepsis, Endocarditis
67
If the causative organism is unknown, what should gentamicin be combined with?
Penicillin and/or metronidazole - because lacks activity against streptococci or anaerobes
68
2 main side effects of gentamicin
Triggers apoptosis of specific epithelium, causing: Nephrotoxicity (potentially reversible) Ototoxicity (may be irreversible) It is therefore important to monitor plasma drug concentrations, measure renal function, and ask patient daily if they have noticed any ear symptoms
69
ROA of gentamicin
IV infusion diluted with NaCl 0.9% to prevent exposure of ear to high concentration bolus - cannot be given orally as does not cross lipid membranes
70
What happens when macrolides bind to the 50S subunit?
Blocks translocation and therefore elongation
71
Spectrum of activity of erythromycin
Relatively broad spectrum against Gram-positive and some Gram-negative bacteria
72
Compared to erythromycin, clarithromycin has increased activity against...
Gram-negative bacteria (especially H. influenza) - it is synthetic
73
Triple therapy for H. pylori eradication
PPI + Clarithromycin + Amoxicillin or Metronidazole
74
Which macrolide produces the worst side effects?
Erythromycin
75
Antibiotics associated with increased risk of colitis - i.e. C. difficile infection
Amoxicillin, Tazocin, FLucloxacillin Cephalosporins (& carbapenems) Macrolides, e.g. Clarithromycin Quinolones, e.g. Ciprofloxacin
76
Side effects of macrolides
GI upset when taken orally (N&V, abdominal pain, diarrhoea) Thrombophlebitis when taken IV Allergy Antibiotic-Associated colitis Liver abnormalities Prolonged QT interval (predisposing to arrhythmias) Otoxicity at high doses
77
Macrolides should be used with caution alongside drugs that prolong the QT interval
Amiodarone, antipsychotics, quinine, quinolines, SSRIs
78
Do erythrmoycin & clarithromycin inhibit or potentiate cytochrome P450?
Inhibit - therefore drugs metabolised by cytochrome P450 will have increased concentrations & risks of AEs - warfarin & bleeding, statins & myopathy
79
Elimination of macrolides
Mostly hepatic
80
What are quinolines particularly active against?
Gram-negative bacteria (urinary & GI infections)
81
Why are quinolines, e.g. ciprofloxacin, not used readily (reserved as second or third-line for UTIs, severe GI, LRTI)
Bacteria rapidly develop resistance to quinolines + it has an association with C. difficile
82
Metronidazole works by...
Entering bacterial cell walls by passive diffusion. Reduction generates a free radical that binds to DNA & causes bacterial death. (Aerobic bacteria are unable to reduce metronidazole)
83
Metronidazole is active against...
Anaerobes (Gram-positive & Gram-negative). Which is why it is an "anaerobic antimicrobial"
84
Infections that metronidazole is indicated for...
``` Gram-positive anaerobe: -C. difficile Gram-negative anaerobes: -Oral infections & aspiration pneumonia -Surgical & gynaecological infections Protozoal infections: -Trichomonal vaginal infection -Giardiasis ```
85
What cannot be consumed with metronidazole?
Alcohol (during or 48hrs afterwards) - flushing, headache, nausea, vomiting Because it inhibits acetaldehyde dehydrogenase which is responsible for clearing the intermediate alcohol metabolite acetaldehyde from the body
86
Why is antimicrobial efficacy of metronnidazole reduced by phenytoin and rifampicin?
Induce cytochrome P450, which reduces plasma concentrations of metronidazole
87
ROA of metronidazole
Variety: oral, IV, rectal, gel
88
Glycopeptides (vancomycin) are active against?
Gram-positive bacteria only (aerobic & anaerobic)
89
Indications for glycopepetides
Gram-positive infection (e.g. endocarditis) & Antibiotic-associated colitis caused by C. difficile
90
Side effects of vancomycin
``` Thrombophlebitis at site of infusion Severe reactions if infused rapidly Hypersensitivity Nephrotoxicity Otoxicity Blood disorders ```
91
What is Augmentin?
Co-amoxiclav - i.e. contains penicillin

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