2: Antimicrobials 1 Flashcards
(43 cards)
3 targets of antimicrobials
Peptigolycan layer of cell wall
Inhibition of bacterial protein synthesis
DNA gyros and other prokaryote specific enzymes
what are the 2 types of inhibitors of cell wall synthesis and examples of them, differences
B-lactam abx = penicillins, cephalosporins, carbapenems
- Broad spectrum
Glycopeptides = vancomycine, teicoplanin
- Gram +ve
Gram +ve vs Gram -ve
Gram-positive cell wall – thick peptidoglycan cell wall (made of NAG and NAM components)
Gram-negative cell wall – thinner peptidoglycan cell wall, outer membrane conferring resistance to some antibiotics
- Can be more resistant and harder to treat due to outer membrane
How do B-lactams work?
Inactivate enzymes involved in terminal stages of cell wall synthesis = transpeptidases / penicillin binding proteins
- Beta lactam is a structural analogue of the enzyme substrate
Bactericidal (active against rapidly dividing bacteria) – if cell wall has already been formed, they haveno effect**
- Ineffective against bacteria lacking peptidoglycan cell walls (mycoplasma, chlamydia)
- Cause cell lysis
Give examples of penicillins (5)
Penicillin
Amoxicillin
Flucloxacillin
Piperacillin
Clavulanic acid + amoxicillin (co-amoxiclav) and tazobactam (tazocin/piptazobactam)
Penicillin
gram +ve, streptococci, clostridia
- Broken down by beta lactamase (produced by SA and many other gram -ve organisms)
- Allergy – need to get a clear history
Amoxicillin
broad-spectrum (enterococci to gram -ve)
- Broken down by beta lactamase (produced by SA and many other gram -ve organisms)
Flucloxacillin
SA
- Not broken down by beta-lactamase produced by SA
- Similar to penicillin, less reactive
Piperacillin
broad-spectrum (pseudomonas, non-enteric gram -ve)
- Broken down by beta lactamase (produced by SA and many other gram -ve organisms)
- Similar to amoxicillin
Co-amoxiclav and tazobactam
- Clavulanic acid = beta lactamase inhibitors → protect penicillin from enzymatic breakdown
- Increase coverage to include SA, gram -ve (i.e. E. coli), anaerobes
What bacteria (G+ve) produced b-lactamase?
Staph aureus
Give examples of cephalosporins (4)
Cefuroxime
Ceftriaxone
Ceftazidime
Cefotaxime
Cefuroxime
- Stable to many beta lactamases made by gram -ve
- Similar cover to co-amox (less active against anaerobes)
Ceftriaxone
- Associated with C. difficile
- Treat meningitis (IM ceftriaxone)
- NO COVER against Pseudomonas
Ceftazidime
- Activity against pseudomonas (HAIs often)
Cefotaxime
The paediatric ceftriaxone
Give examples of Carbapenems
Meorpenem, imipenem, ertapenem (STABLE TO ESBL enzymes)
Give an example of monobactams
carumonam
Key features of beta lactase
- Relatively non-toxic
- Renally excreted so decrease dose if renal impairment
- Short T1/2 (many are type 2 drugs so aim to maximise the time > MIC)
- Will not cross BBB
- Cross allergenic – penicillin has 10% cross reactivity with cephalosporins and carbapenems
Glycopeptides
Active against gram +ve (inhibit cell wall synthesis)
- Large molecules so unable to penetrate gram -ve
Important uses:
- MRSA infections (IV)
- C. difficile infection (oral – Vancomycin, teicoplanin)
Slowly bactericidal
Nephrotoxic – must monitor for accumulation
Gove 5 examples of inhibitors of protein synthesis
Aminoglycosides
Tetracyclines
Macrolides
Chloramphenicol
Oxazolidinones
Give 3 examples of aminoglycosides
Gnetamicin, amikacin, tobramycin
G-ve action
Aminoglycoside MoA
- Bind to amino-acyl site of 30s ribosome subunit
- Rapid, concentration-dependent bactericidal
- Require specific transport mechanisms to enter
- Accounts for some intrinsic resistance
- Ototoxic and nephrotoxic – monitor levels
- Gentamicin and tobramycin are particularly active against pseudomonas aeruginosa
-
Synergistic combination with beta lactams
- Endocarditis treatment, pneumonia
- No activity against anaerobes
tetracylines MoA
Broad spectrum, activity against intracellular pathogens – chlamydia, rickettsia, mycoplasma
Bacteriostatic (stops bacteria from reproducing)
Widespread resistance now
Deposited in growing bone
- Don’t give to children, pregnant women
- SE: photosensitivity rash (summer effect)
TETRACYLINE, DOXYCYCLINE