Antimicrobials

Question 1

Which antibiotics have a higher risk of causing C. diff?

Answer 1

Cephalosporins, quinolones and clindamycin

Question 2

How do penicillins work?

Answer 2

Penicillins are bactericidal and act by interfering with bacterial cell wall synthesis.

Question 3

What are the adverse effects of penicillins?

Answer 3

Allergy - occurs in 1-10% of exposed individuals with anaphylaxis in <0.05% of treated. Individuals with a history of anaphylaxis, urticaria or rash immediately after penicillin administration are at risk of immediate hypersensitivity to a penicillin. Individuals with a history of a minor rash or one which occurs more than 72 hours after penicillin administration are probably not allergic.

A rare but serious effect is encephalopathy due to cerebral irritation. This may result from excessively high doses or renal failure.

In renal failure, there may also be accumulation of electrolyte since most injectable penicillins contain sodium or potassium.

Diarrhoea frequently occurs

Question 4

What is the difference between amoxicillin and ampicillin?

Answer 4

Amoxicillin is a derivative of ampicillin with similar antibacterial spectrum. It is better absorbed when given PO and therefore the preferred oral formulation.

Both are active against Gram-positive and negative organisms but inactivated by penicillinases. Strep pneumoniae is usually sensitive, but almost all Staph, 50% of E. coli and 15% of HiB are now resistant.

Question 5

What are some of the indications for amoxicillin?

Answer 5

Otitis media, sinusitis, oral infections, bronchitis/IE COPD, CAP, H. influenzae infections, invasive salmonellosis, listerial meningitis.

Question 6

Why should ampicillin/amoxicillin not be used in glandular fever?

Answer 6

Can cause a maculopapular rash

Question 7

What is co-amoxiclav made up of?

Answer 7

beta-lactamase inhibitor clavulanic acid plus amoxicillin

Question 8

What are the indications for co-amoxiclav?

Answer 8

Infections likely to be caused by amoxicillin-resistant beta-lactamase-producing strains.

Question 9

What is an additional warning of co-amoxiclav in addition to those for amoxicillin?

Answer 9

Cholestatic jaundice. The risk of acute liver toxicity is about 6 times greater with co-amoxiclav than with amoxicillin.

Question 10

When is flucloxacillin used?

Answer 10

Flucloxacillin is not inactivated by penicillinases which are produced by most staphylococci and therefore used for these.

Question 11

Which penicillins are used against pseudomonal infections?

Answer 11

Ticarcillin or piperacillin (usually with clavulanic acid) with gentamicin are used for serious pseudomonal infections.

Question 12

When is Pen V used?

Answer 12

For streptococcal sore throats and prophylaxis after splenectomy.

Question 13

How do cephalosporins work?

Answer 13

Inhibit mucopeptide synthesis in the bacterial cell wall, making osmotically unstable organisms susceptible to cell lysis.

Question 14

What are the adverse effects of cephalosporins?

Answer 14

Hypersensitivity - about 0.5-6.5% of penicillin-sensitive patients will also be allergic to cephalosproins. Patients with a history of immediate hypersensitivity to penicillin should not receive a cephalosporin.

Question 15

Give an example of a second generation cephalosporin and its use.

Answer 15

Cefuroxime - greater activity against H. influenzae and N. gonorrhoeae.

Question 16

Which are third generation cephalosporins?

Answer 16

Cefotaxime, ceftazidime and ceftriaxone

Question 17

What are the indications for ceftriaxone?

Answer 17

Serious infections such as septicaemia, pneumonia and meningitis.

Question 18

How do macrolides work?

Answer 18

Inhibit protein synthesis by binding to 50S ribosomal subunits. Bacteristatic

Question 19

What are the indications for macrolides?

Answer 19

Similar spectrum to penicillins therefore used as an alternative in penicillin-allergic patients. Indications include respiratory infections, whooping cough, Legionnaires disease and campyolobacter enteritis.

Erythromycin is also active against Chlamydia, legionella and mycoplasmas and is therefore indicated in severe CAP where these organisms may be suspected.

Question 20

What are the side effects of macrolides?

Answer 20

Common: GI intolerance, diarrhoea, phlebitis with IV administration
Occasional: cholestatic hepatitis, generalised rash, prolonged QTc, raised LFTs

Question 21

What drugs do erythromycin interact with?

Answer 21

Erythromycin is a substrate of CYP3A4 and a potent inhibitor of CYP3A4 and CYP1A2. The most important interactions are:

1) Theophylline - increase serum levels
2) Warfarin - may increase anticoagulant effect
3) Statins - increased risk of myositis

Question 22

How do tetracyclines work?

Answer 22

Inhibit protein synthesis by binding to 30S ribosomal subunit.

Question 23

What are contra-indications to tetracyclines?

Answer 23

Deposition of tetracyclines in growing bone and teeth causes staining and occasionally dental hypoplasia and should not be given to children under 12 or to pregnant or breast-feeding women.

Question 24

What are the adverse effects of tetracyclines?

Answer 24

Common: GI intolerance, stained/deformed teeth, diarrhoea
Rare: exacerbation of renal failure (except doxycycline), hepatitis, dysphagia/oesophageal ulcerations, candidiasis

Question 25

Why is doxycycline preferred to other tetracyclines?

Answer 25

Once daily dosing
Can be safely used in renal failure
No interactions with food
Considered first line agent for COPD exacerbation in penicillin allergic patients.

Question 26

How do quinolones work?

Answer 26

Inhibition of DNA topoisomerases by binding to DNA-enzyme complexes.

Question 27

What are the indications for quinolones?

Answer 27

Respiratory tract infections (except pneumococcal pneumonia), UTIs, GI infections (including typhoid), bone and joint infections, gonorrhoea and septicaemia

Now a second line agent because of higher risk of C. diff

Question 28

What are the adverse effects of quinolones?

Answer 28

Occasional: nausea and diarrhoea, CNS - headache, malaise, insomnia, restlessness and dizziness
Rare: tendon rupture, QTc prolongation, raised transaminases/ liver failure, peripheral neuropathy, severe allergic reactions, intersitial nephritis

Question 29

What are the contraindications to quinolones?

Answer 29

Pregnancy, breast feeding, epilepsy (lowers seizure threshold)

Question 30

How do aminoglycosides work?

Answer 30

Inhibit protein synthesis by irreversibly binding to 30S ribosomal subunit

Question 31

What is gentamicin used to treat?

Answer 31

It is the aminoglycoside of choice in the UK and is widely used for the treatment of serious infections including UTI, intra-abdominal sepsis and sepsis of unknown origin. It has a broad spectrum but is inactive against anaerobes and has poor activity against haemolytic streptococci and pneumococci. It is also active against Pseudomonas aeruginosa.

Question 32

What is streptomycin used for?

Answer 32

TB

Question 33

How are aminoglycosides given?

Answer 33

Not absorbed from the gut and therefore given by injection for systemic infections. Excretion is principally via the kidney and accumulation occurs in renal impairment.

Question 34

What are the adverse effects of aminoglycosides?

Answer 34

Mainly dose-related, so whenever possible treatment should not exceed 7 days. The main side-effects are ototoxicity and nephrotoxicity.

Aminoglycosides may also impair neuromuscular transmission and should not be given to patients with myasthenia gravis.

Question 35

How should aminoglycoside doses be adjusted in renal impairment?

Answer 35

Interval between doses must be increased; if the renal impairment is severe the dose itself should be reduced.

Question 36

Which drugs should you avoid with aminoglycosides?

Answer 36

Should preferably not be given with potentially ototoxic diuretics e.g. furosemide.

Question 37

What are the adverse effects of metronidazole?

Answer 37

Common: GI intolerance, metallic taste, headache, dark urine
Occasional: peripheral neuropathy, phlebitis and disulfiram-like reaction with alcohol