Antimicrobials 1 Flashcards
(55 cards)
Gram positive vs. Gram negative
Gram positive = Thick peptidoglycan layer - catches Gram stain - purple
Gram negative = Thin peptidoglycan layer + outer LPS membrane - pink
What is the MoA of B-lactams?
B-lactam ring binds and inactivates transpeptidases that form cross links between peptidoglycan monomers in cell wall - weak cell wall = lysis
BACTERICIDAL to rapidly dividing daughter cells forming cross-links only - not active on stable cell walls already formed
Which bacteria lack a cell wall?
Mycoplasma, chlamydia, RIckettsia (B-lactams don’t work)
What are the 6 main types of penicillin? (B-lactam 1)
SA resistant:
- (Benzyl)penicillin - still most potent but narrow spectrum - Gram positive only but not S aureus
- Amoxicillin - broader spectrum to some Gram negs (E coli) but not S aureus
- Piperacillin - even broader spectrum (covers Pseudomonas + more Gram negs) but not S aureus
SA sensitive: (new approaches)
- Flucloxacillin - similar spectrum to penicillin + mainstay against S aureus
- Co-amoxiclav = amoxicillin + clavulinic acid (B-lactamase inhibitor)
- Tazocin = piperacillin + tazobactam (B-lactamase inhibitor)
What does SA produce that makes it resistant to B-lactams?
B-lactamase - degrades B-lactam ring that binds transpeptidase
Why is flucloxacillin favoured over Co-amox/Tazocin in difficult to access infections?
E.g. deep skin infections with lots of necrotic tissue, osteomyelitis
Don’t have to get 2 drugs into infection
3 generations of cephalosporins
B-lactams 2
1st gen - Cephalexin
2nd gen - cefuroxime
3rd gen - cefotaxime, ceftriaxone, ceftazidime
- All stable to B-lactamases but not ESBLs
- Increasing activity against Gram negatives, reducing activity against Gram positives
What happens to cephalosporin activity from 1st to 3rd generation?
Gram negative activity increases
Cephalosporin in meningitis
Ceftriaxone
Gram negative cocci
Cephalosporin for Pseudomonas
Ceftazidime
Cephalosporin with similar cover to co-amoxiclav but favoured as one drug
Cefuroxime
Needs to be combined with metronidazole to cover anaerobes
Cefuroxime (cef + met)
Carbapenems
B-lactams 3
- Stable to ESBLs but now carbapenemases are a problem
- Reserved for high-risk mutli-drug resistance bacteria - most powerful B-lactams
3 types of B-lactam
Penicillins
Cephalosporins
Carbapenems
Inhibit cell wall synthesis
B-lactams
Glycopeptides
MoA of glycopeptides
Lodge into cell wall to physically block transpeptidases forming cross links - weak cell = lysis
BACTERICIDAL to daughter cells again
Two examples of glycopeptides
Vancomycin
Teicoplanin
Glycopeptide indications
- Gram positive only. Very large molecules that can’t get through outer membrane of Gram negative (except Neisseria)
- Used in tricky MRSA and C difficile infections
- Nephrotoxic - monitor levels
Inhibitors of protein synthesis
Bind 30S: Aminoglycosides, tetracyclines
Bind 50S: Macrolides, chloramphenicol
Bind 23S: Linezolid
What is unusual about the aminoglycosides?
All inhibitors of protein synthesis are bacteriostatic (prevent division) except aminoglycosides (bactericidal)
Mechanism unknown
AminoGlycoside Binds 30S Pseudomonas Ototoxic + nephrotoxic B-lactam synergy Gram negatives
Gentamicin
Tetracycline Binds 30S Bacteria without cell wall + MRSA Deposit in bone - teeth staining, enamel hypoplasia Bad rash in sunlight
Doxycyline
Binds 50S
Mild staph + strep infections in penicillin allergic
Atypical pneumonias (Legionella, Mycoplasma)
Campylobacter gastroenteritis
Macrolides (erythromycin, clarithromycin, azithromycin)
- New-old (newer agents longer half-life so better in paediatrics)
Binds 50S
2nd line meningitis
Risk of aplastic anaemia
Grey baby syndrome
Chloramphenicol
