Antimicrobials Flashcards
Which antibiotics have a higher risk of causing C. diff?
Cephalosporins, quinolones and clindamycin
How do penicillins work?
Penicillins are bactericidal and act by interfering with bacterial cell wall synthesis.
What are the adverse effects of penicillins?
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
What is the difference between amoxicillin and ampicillin?
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.
What are some of the indications for amoxicillin?
Otitis media, sinusitis, oral infections, bronchitis/IE COPD, CAP, H. influenzae infections, invasive salmonellosis, listerial meningitis.
Why should ampicillin/amoxicillin not be used in glandular fever?
Can cause a maculopapular rash
What is co-amoxiclav made up of?
beta-lactamase inhibitor clavulanic acid plus amoxicillin
What are the indications for co-amoxiclav?
Infections likely to be caused by amoxicillin-resistant beta-lactamase-producing strains.
What is an additional warning of co-amoxiclav in addition to those for amoxicillin?
Cholestatic jaundice. The risk of acute liver toxicity is about 6 times greater with co-amoxiclav than with amoxicillin.
When is flucloxacillin used?
Flucloxacillin is not inactivated by penicillinases which are produced by most staphylococci and therefore used for these.
Which penicillins are used against pseudomonal infections?
Ticarcillin or piperacillin (usually with clavulanic acid) with gentamicin are used for serious pseudomonal infections.
When is Pen V used?
For streptococcal sore throats and prophylaxis after splenectomy.
How do cephalosporins work?
Inhibit mucopeptide synthesis in the bacterial cell wall, making osmotically unstable organisms susceptible to cell lysis.
What are the adverse effects of cephalosporins?
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.
Give an example of a second generation cephalosporin and its use.
Cefuroxime - greater activity against H. influenzae and N. gonorrhoeae.
Which are third generation cephalosporins?
Cefotaxime, ceftazidime and ceftriaxone
What are the indications for ceftriaxone?
Serious infections such as septicaemia, pneumonia and meningitis.
How do macrolides work?
Inhibit protein synthesis by binding to 50S ribosomal subunits. Bacteristatic
What are the indications for macrolides?
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.
What are the side effects of macrolides?
Common: GI intolerance, diarrhoea, phlebitis with IV administration
Occasional: cholestatic hepatitis, generalised rash, prolonged QTc, raised LFTs
What drugs do erythromycin interact with?
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
How do tetracyclines work?
Inhibit protein synthesis by binding to 30S ribosomal subunit.
What are contra-indications to tetracyclines?
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.
What are the adverse effects of tetracyclines?
Common: GI intolerance, stained/deformed teeth, diarrhoea
Rare: exacerbation of renal failure (except doxycycline), hepatitis, dysphagia/oesophageal ulcerations, candidiasis
Why is doxycycline preferred to other tetracyclines?
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.
How do quinolones work?
Inhibition of DNA topoisomerases by binding to DNA-enzyme complexes.
What are the indications for quinolones?
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
What are the adverse effects of quinolones?
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
What are the contraindications to quinolones?
Pregnancy, breast feeding, epilepsy (lowers seizure threshold)
How do aminoglycosides work?
Inhibit protein synthesis by irreversibly binding to 30S ribosomal subunit
What is gentamicin used to treat?
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.
What is streptomycin used for?
TB
How are aminoglycosides given?
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.
What are the adverse effects of aminoglycosides?
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.
How should aminoglycoside doses be adjusted in renal impairment?
Interval between doses must be increased; if the renal impairment is severe the dose itself should be reduced.
Which drugs should you avoid with aminoglycosides?
Should preferably not be given with potentially ototoxic diuretics e.g. furosemide.
What are the adverse effects of metronidazole?
Common: GI intolerance, metallic taste, headache, dark urine
Occasional: peripheral neuropathy, phlebitis and disulfiram-like reaction with alcohol
