Wk6 - clinical microbiology 1 Flashcards
(143 cards)
Structure of gram +ve bacteria wall
Cell membrane
Thick peptidoglycan cell wall
Structure of gram -ve bacteria wall
Cell membrane
Peptidoglycan cell wall
Outer membrane
Periplasm
Bacteriocidal
Achieve sterilisation of the infected site by directly killing the bacteria
Lysis of bacteria can lead to release of toxins and inflammatory material
Bacteriostatic
Suppresses growth but does not directly sterilise infected site
Requires additional factors to clear bacteria - immune mediated killing
Antibiotic spectrum
Spectrum refers to the range of bacterial species effectively treated by the antibiotic
Broad spectrum of antibiotics
Antibiotics that are active against a wide range of bacteria
Treat most causes of infection but also have a substantial effect on colonising bacteria
Action of Meropenem
Active against almost all gram +ve and gram -ve species.
Resistance is rare except
Broad spectrum antibiotic
Action of Benzyl-pencillin
Highly active against streptococci.
Most other disease causing bacteria are resistant
Narrow spectrum antibiotic
Narrow spectrum of antibiotics
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
Different ways of using antibiotics (different therapies)
Guided therapy:
Depends on identifying cause of infection and selecting agent based on sensitivity testing
Narrow spectrum options - mostly
Empirical therapy:
Best (educated) guess therapy based on clinical/epidemiological acumen
Used when therapy cannot wait for culture
Broad spectrum - mostly
Prophylactic therapy:
Preventing infection before it begins
Antibiotic associated harm
Disruption of bacterial flora leads to:
Overgrowth with yeasts – thrush
Overgrowth of bowel – diarrhoea
Antibiotic use associated with:
development of C. difficile colitis
future colonisation and infection with resistant organisms
Beta-Lactam antibiotics - 4 main types
Penicillins
Cephalosporins
Carbapenems
Monobactams (Aztreonam)
Main examples of beta-lactam antibiotics
Benzylpenicillin Flucloxacillin Amoxicillin Ceftriaxone Meropenem Aztreonam
Mechanism of action of beta-lactams
All β-lactams share the same structural feature
β-lactam motif analogue of branching structure of peptidoglycan
Inhibits crosslinking of cell wall peptidoglycan
Causes lysis of bacteria - bacteriostatic
Beta-lactamases
Enzymes that lyse and inactivate beta-lactam drugs
Commonly secreted by Gram –ves and S. aureus
Confer high level resistance to antibiotic:
Total antibiotic failure is likely to result
How are beta lactams given?
Most β-lactams poorly absorbed from GI tract:
must be given IV
Some can be effective orally:
amoxicillin, flucloxacillin most commonly used
Vomiting limits dose
Half life of e.g.s of beta lactams
Benzylpenicillin ≈ 1 hour
Ceftriaxone ≈ 8 hours
Adverse effects of beta-lactams
Usually very well tolerated, eveen in high doses
GI toxicity, n&v, diarrhoea, cholestasis
Infection - candidiasis, c.diff
HYpersensitivity - Type 1 - anaphylaxis, Type 4 - mild to seevre dermatology, Iterstitial nephritis
Rare: seizure, haemolysis, leukoaenia
Type 1 hypersensitivty
Relatively common allergy (0.7 – 4% of penicillin courses)
Most patients develop an urticarial rash
Anaphylaxis is the most feared complication
Cross reaction between classes is variable
Cross reactivity
Patients allergic to a penicillin will usually be allergic to other penicillins
Cross reactivity with other antibiotic classes is much lower
Some patients with penicillin allergy may be safely managed with other β-lactams
Particularly important if patient presents with life-threatening infection (esp. meningitis)
Features of Benzylpenicillin
MOA of beta-lactams - Penicillins
Chemically similar to original penicillin
Administered by the intra-venous route
There is an oral agent (Penicillin V) but not often used
Remains the first choice antibiotic for serious streptococcal infection (i.e. erysipelas)
Narrow spectrum agent
MOA:
Attaches to penicillin-binding proteins on forming bacterial cell walls.
This inhibits the transpeptidase enzyme which cross-links the bacterial cell wall.
Failure to cross-link induces bacterial cell autolysis.
Amoxicillin provides some amount of gram-negative cover in addition to gram-positive drugs
Features of Amoxicillin
Semi-synthetic penicillin:
- Greatly increased activity against gram negative organisms (although resistance is now common)
- Much more orally bioavailable than natural penicillins
Widely used in the treatment of a wide range of infections
A lot of resistance to Amoxicillin now
Used against Streptococci (resp. tract infections)
FEatures of FLucloxacillin
Synthetic penicillin developed to be resistant to beta-lactamase produced by staphylococci
Antibiotic highly active against:
Staphylococcus aureus (not MRSA)
Streptococci
No activity at all against gram negative organisms
Can be given orally but nausea limits dose
Beta-lactamase inhibitors
Effectively inhibit some beta-lactamases
Co-administered with penicillin antibiotic
Greatly broadens spectrum of penicillins against Gram –ves and S. aureus
There are many beta-lactamases that are not inhibited leading to antibiotic failure
Co-amoxiclav - broad spectrum
Tazocin - very broad spectrum