Antibiotics Part 2 Flashcards
What are the four possible targets of antibiotics?
Cell wall biosynthesis
Protein biosynthesis
DNA and RNA replication
Folate metabolism
What do protein synthesis inhibitors actually inhibit?
Either the 50S or the 30s ribosomal subunits, so that protein transplation can’t occur
Which antibiotics inhibit the 50S ribosomal subunit?
Macrolides (erythromycin, clarithromycin and azithromycin)
Clindamycin
Chloramphenicol
Which antibiotics inhibit the 30S ribosomal subunit?
Aminoglycosides (gentamicin)
Tetracyclines (doxycycline)
What bacteria are macrolides active against?
Good spectrum against gram positives and respiraotry gram negatives. Active against 'atypicals' - legionella - mycoplasma - chlamydia
How are macrolides administered?
Orally - excellent oral absorption even in severe infection
What are ‘atypical’ bacteria?
Bacteria that don’t colour with gram staining (remain colourless). They are neither gram positive or gram negative
List some of the possible complications of Macrolides.
Diarrhoea and vomiting
QT prolongation - can lead to arrhythmias
Hearing loss with long term treatment (not a problem for short courses)
What are some of the importance drug interactions of Clarithromycin (a macrolide)?
Simvastatin - avoid co-prescription by temporarily stopping Simvastatin
Atorvastatin - similar to above
Warfarin - only an issue if the patient isn’t being regularly monitored
Is resistance to macrolides common?
Resistance among typical pathogens is relatively common (can be used in non-severe infections)
Resistance among atypical pathogens is relatively rare (included in treatment for severe infections to cover these organisms)
What are the similarities between Clindamycin and macrolides?
Same mechanism of action
Excellent oral absorption
Principle action is against gram positives
What are the key differences between Clindamycin and macrolides?
No action against aerobic gram negatives or atypical bacteria
Excellent activity against anaerobes
What antibiotic would be added to patients with a gram positive toxin mediated disease, and why?
Clindamycin beause it is highly effective at stopping exotoxin production
Give some examples of gram positive mediated disease?
Toxic shock syndrome
Necrotising fasciitis
What is the main side effect of Clindamycin?
Because it is very active against anaerobes, it effectively disrupts the colonic flora.
- this leads more easily to a C.diff infection
(all antibiotics cause CDI to a small extent)
Why does C.diff commonly colonise the gut after antibiotic use?
Antibiotics dramatically after the colonic flora
C.diff easily colonises and forms spores which are difficult to eradicate as they can remain inactive until put under stress.
C.diff has developed resistance against common antibiotic classes
Which antibodies most commonly cause C.diff infections?
4 C’s
- Clindamycin
- Co-amoxiclav (broad)
- Cephalosporins
- Ciprofloxacin
How can the disruptive properties of antibiotics on colonic flora be minimised?
Keep antibitoics as narrow spectrum as possible
Use a faecal transplant to re-balance gut flora
Chloramphenicol is broad spectrum, which means its very toxic, causing….
Bone marrow suppression (aplastic anaemia)
Optic neuritis
What are the modern uses of chloramphenicol?
Topical therapy to eyes
- doesn’t cause BM suppression (not administered systemically)
Bacterial meningitis with beta-lactam allergy
Why has use of aminoglycosides increased more in the last 5 years?
Improved dosing regimens
Restriction of other broad spectrum antibiotics
Which bacteria is Gentamicin (an aminoglycoside) active against?
Excellent gram negative coverage (some gram positive effects), so a different class is needed to treat gram positive as well
Describe the action of Gentamicin when it binds to the 30S ribsome
Reversibly binds to the 30S ribosome
- bacteriostatic action (stops bacterial growing)
- results in prolonged post-antibiotic effect
Does Gentamicin have a bacteriostatic or bactericidal action?
Both
- bacteriostatic action by binding to the 30S ribosome
- bactericidal actionon the cell membrane, resulting in rapid killing early in the dosing interval
What are the possible toxic effects of aminoglycosides (including gentamicin)
Nephrotoxicity
Ototoxicity (hearing loss, loss of balance and oscillopsia)
Neuromuscular blockade (only significant in myaesthenia gravis)
Why are aminoglycosides given as once-daily dosing?
Risk of toxicity
- given a high initial dose to take advantage of rapid killing
- leave long dosing interval
- measure tough level to ensure drug isn’t accumulating