Beestjes wk 6 Flashcards
Name a bacteriostatic antibiotic
clarithromicin
Antibiotic Spectrum
the range of bacterial species effectively treated by the antibiotic
NB: Important to distinguish between lack of activity and resistance. Spectrum normally refers to wild type bacteria (i.e. those that haven’t yet acquire resistance genes)
Broad Spectrum Abx
Antibiotics that are active against a wide range of bacteria
downside- also have a substantial effect on colonising bacteria. tend to cause other infections like C. diff and candida
Narrow Spectrum
Antibiotics that are active against a limited range of bacteria
Useful only where the cause of the infection is well defined
Have a much more limited effect on colonising bacteria
Guided therapy
Depends on identifying the cause of infection and selecting agent based on sensitivity testing
Used principally for relatively mild infections for which treatment can be delayed until the results of a lab culture are available
Empirical therapy
Used when therapy cannot wait for culture, i.e. in patients with more severe infections:
- Sepsis
- Bacterial meningitis
Use antibiotic which has extensive action against any bacteria which might be causing infection
Need to penetrate broadly throughout body because the site of infection may be unknown or the infection may be disseminated.
Prophylactic therapy:
Used to prevent an infection before it begins
May be used in healthy people who have been exposed to:
- Surgery → e.g. hip replacements, bone marrow transplants, colorectal surgery
- Injury
- Infective material
Also used in immunocompromised individuals:
- HIV
- Transplantation
- Splenectomy
β-lactam antibiotics
Defined by the presence of a beta-lactam ring
This ring is structurally analogous to peptidoglycan that makes up the bacterial cell wall
Beta lactam antibiotics are penicillin binding protein inhibitors → stop the development of the cell wall
Interfere with peptidoglycan metabolism, and impair the bacteria’s ability to lay down the cell wall by inhibiting cross-linking
Beta lactams cause cell lysis -> bactericidal
Classes of β-lactam antibiotics
1) penicillins
2) cephalosporins
3) Carbapenems (usually the broadest spectrum)
4) Monobactams
5) Combinations
PCCMC
List 3 penicillins
1) benzylpenicillin
2) amoxicillin
3) flucloxacillin
Name a cephalosporin
Ceftriaxone
Name a carbepenem
meropenem
Name a monobactam
aztreonam
Name two beta lactam combination drugs
1) co-amoxiclav = Amoxicillin/clavulanic acid (Augmentin)
2) Piperacillin/tazobactam (Tazocin)
Beta lactamases
Enzymes that lyse and inactivate beta-lactam drugs
Confer high level resistance to antibiotic
what classes of bacteria commonly secrete beta lactams?
Gram negatives and S.aureus
Beta lactam absorption
Most β-lactams poorly absorbed from GI tract:
must be given IV
Which β-lactams can eb given orally?
1) amoxicillin
2) flucloxacillin
NB: vomiting limits dose
β-lactam excretion
Usually excreted unchanged in urine, some also via bile
renal function is therefore the key determinant in beta lactam dosing
β-lactam adverse effects
By and large very safe even in very high doses.
GI effects are the most common - nausea, vomiting, diarrhoea, cholestasis
Other:
- hypersensitivity t1 = urticaria, anaphylaxis (rare)
- t2 hypersensitivity -= haemolytic anaemia
- t3 = vasculitis
- t4 hypersentsitivity - mild to severe = 4th day rash to stevens johnson syndrome
β-lactam allergy
1/10 reports penicillin allergy
Often reported hypersensitivity syndrome is non-allergic
cross reactivity = Patients allergic to a penicillin will usually be allergic to other penicillins
Benzylpenicillin administration
IV
NB: oral agent (Penicillin V) is similar but not often used
Benzylpenicillin spectrum/activity
Narrow spectrum
first choice antibiotic for serious streptococcal infection
also has good activity against neisseria
first choice antibiotic for serious streptococcal infection
Benzylpenicillin
Amoxicillin administration
Much more orally bioavailable than natural penicillins
most commonly used beta lactam
Amoxicillin
Amoxicillin spectrum/activity
principally used against streptococci because of extensive resistance
e.g. in upper respiratory tract infections
also has good activity against enterococci
Flucloxacillin
Synthetic penicillin developed to be resistant to beta-lactamase produced by staphylococci
Flucloxacillin spectrum/activity
highly active against Staphylococcus aureus (not MRSA)
Streptococci (mildly effective)
No activity at all against gram negative organisms
Flucloxacillin administration
Can be given orally but nausea limits dose
Effect of Beta-lactamase inhibitors
Effectively inhibit some beta-lactamases
Greatly broadens spectrum of penicillins against Gram negatives and S. aureus
How does the susceptibility of cephalosporins to beta lactmases compare to that of penicillins?
Less Susceptible To beta-lactamases than penicillins because of the presence of a side chain (their structure is more complicated)
Carbapenems spectrum and use
Ultra-broad spectrum beta-lactam antibiotics
should be held back for patients in who it is really necessary
Excellent spectrum of activity against Gram +ves and Gram –ves
No activity against MRSA
Resistant to beta- lactama
What are CPEs?
cabapenemase producing Enterobacteriaceae
New beta-lactamases that lyse carbapenems
Which beta lactam can be given to patients who are penicillin allergic?
Aztreonam (monobactam)
structure is very different to penicillin therefore no cross reactivity to penicillins (except anaphylactic allergy)
Aztreonam administration
Only given IV – no oral absorption
Which drug can be used as a substitute for gentamicin in patients who can’t have gentamicin due to renal toxicity?
Aztreonam
Vancomycin mechanism of action
Inhibits cell wall formation in Gram +ves only
no Gram –ve action - the molecule is too large to get through the outer membrane
Not dependent on PBP (penicillin binding proteins) binding so effective against resistant organisms who have mutated their penicillin binding protein
Vancomycin spectrum
Broad-spectrum antibiotic
- clostridium
- streptococcus
- enterococcus
- staphylococcus
Vancomycin administration/uses
Indicated for penicillin-allergic patients who cannot receive, or who have failed to respond to penicillin/cephalosporin-antibiotics
Main use is in the treatment of MRSA infection
Not absorbed from GI tract so almost always given IV
Careful drug monitoring is required due to narrow therapeutic index. Main issue in clinical use is underdosing
Oral route only used for treatment of C. diff
vancomycin toxicity
1) Nephrotoxicity – more likely with higher doses
2) hypersensitivity - red man syndrome and anaphylaxis
3) ototoxicity (rare)
Which antibiotic would you prescribe for cellulitis?
Flucloxacillin
Protein synthesis inhibitors targeting the 50S Ribosomal Subunit
1) macrolides -> erythromycin, clarithromycin, azithromycin
2) clindamycin
3) chloramphenicol
Protein synthesis inhibitors targeting the 30S Ribosomal Subunit
1) aminoglycosides -> gentamycin
2) tetracyclines - > doxycycline
Protein synthesis inhibitors
1) macrolides
2) aminoglycosides
3) tetracyclines
macrolides spectrum
Good activity against Gram positive pathogens and respiratory Gram negatives (haemophilus and moraxella)
Most commonly used macrolide
clarithromycin
Active against “atypicals” i.e. organisms causing atypical pneumonia, which is nonresponsive to penicillins
1) Legionella
2) Mycoplasma
3) Chlamydia
Clarithromycin adverse effects
Diarrhoea & Vomiting
QT prolongation
Hearing loss with long term use
Drug interactions
Clarithromycin Drug interactions
over 400 drug interactions
binds to and inhibits CYP-3A4
Statins - Avoid co-prescription. Temporarily stop simvastatin to avoid simvastatin toxicity
Warfarin
Which drug should be stopped if clarythromycin is prescribed?
Statins
clindamycin activity
Principle action against Gram positives
What is useful about clindamycin?
highly effective at stopping exotoxin production because it is such a potent ribosome inhibitor
Added to patients with Gram positive toxin mediated disease because it is thought to add prognostic benefit:
- Toxic shock syndrome
- Necrotising fasciitis
Which antibiotic is given to patients with Gram positive toxin mediated disease to minimise toxin production?
clindamycin
C. Differgic Antibiotics
4C antibiotics:
1) Clindamycin
2) Co-amoxiclav
3) Cephalosporins
4) Ciprofloxacin
Chloramphenicol
inhibits the 50S ribosome
Excellent Broad spectrum of activity
Very toxic:
- Bone marrow suppression
- Aplastic anaemia
- Optic neuritis
Only used for topical therapy to eyes or in bacterial meningitis with beta lactam allergy
Aminoglycosides
30s inhibitors
Aminoglycoside example
gentamicin
Gentamicin mechanism of action
Two mechanisms
1) Bactericidal action on the cell membrane at high concentrations
2) bateriostatic action by binding to 30s ribosomes, causes a prolonged post-antibiotic effect