Antibacterial Agents: Cell Wall Synthesis Inhibition Flashcards
What are the different stages of bacterial cell wall synthesis?
1: cell wall subunits assembly (in CYTOSOL)
2: Linear polymerization of subunits (CELL MEMBRANE)
3: Cross-linking of peptidoglycan polymers (CELL WALL)
What is the mechanism of action for penicillins?
Stage 3 - Cell wall synthesis inhibition
Bactericidal
Describe resistance to penicillins
- Penicillinase production via plasmid in presence of penicillin — Problem w/ MSSA
- Alterations in penicillin-binding proteins – MRSA
- Inability to penetrate outer membrane of g(-) bacteria —- Pen G can’t
Describe the absorption of penicillins
- Moderately strong acids, highly water-soluble
Pen G: IM/IV (poor oral)
Pen V: good po
Dicloxacilin: good po
Amoxicillin: good po
Piperacillin + Beta-lactamase inhibitor: IV only
Describe the distribution of Penicillins
- Distribute throughout body water — penetrate into cells/tissues poorly (b/c it’s ionized at physiological pH)
- Can enter inflamed tissues or membranes (CSF, joints, eyes)
Describe the elimination of penicillins
90% renal excretion
t1/2 = <1-2 hrs
What are narrow spectrum penicillins used for? (E.g. Pen G and V)
G(+) cocci = staph, strep, enterococcus
G(-) cocci = Neisseria
Anaerobes
NOT (!!!!) MSSA, MRSA
What are penicillinase resistant penicillins used for? (E.g. Dicloxacilin)
MSSA skin infections
NOT(!!!!) MRSA
Other than penicillinase-resistant antibiotics, all other PCNs are susceptible to penicillinase unless they are combined with what?
A beta-lactamase inhibitor!!
Amoxicillin-clavulanate
What are extended spectrum penicillins used for? (E.g. amoxicillin)
G(-) RODS = E.coli
G(+) COCCI = staph, strep, enterococcus (less so than Pen G and V)
NOT (!!) MRSA or MSSA
NOT Klebsiella or E.coli (TEM-1)
What are antipseudomonal penicillins used for? (E.g. Piperacillin/Ticarcilin + Beta-lactamase inhibitor)
G(+) COCCI = strep, staph, entero
MSSA
E.Coli, Klebsiella
Pseudomonas, bacteroides, anaerobes!!
What are potential adverse rxns to penicillins?
- Anaphylaxis (Type 1, rare)
- Rash (common)
What are potential adverse rxns to narrow spectrum PCNs?
Convulsions at very high doses
What are potential adverse rxns to extended spectrum PCNs?
- Diarrhea
- Superinfection (CDAD)
What is the mechanism of action for cephalosporins?
Stage 3 - Cell wall synthesis inhibition
Bactericidal
How do cephalosporins differ from PCNs G and V?
- Broader spectrum vs g(-) bacteria
- Less susceptibility to beta-lactamases
- Less cross-reactivity in penicillin sensitive patients
Describe the absorption of cephalosporins
1st gen: Cephalexin (po), Cefazolin (IV only)
2nd gen: Cefaclor (po), Cefuroxime (po, IV)
3rd gen: Cefdinir (po), Ceftriaxone (good CNS penetration!!!)
Describe the distribution of cephalosporins
- Penetrate well into most tissues/fluids (includes placenta)
- Not the case for brain and CSF
- However, 3rd generation can do CNS penetration
Describe the excretion of cephalosporins
- Via kidneys!
- Dose adjustment required w/ renal insufficiency (makes sense) — except w/ ceftriaxone
What are 1st generation cephalosporins used for? (E.g. Cephalexin, Cefazolin)
G(+) COCCI
MSSA
G(-) RODS = E. Coli, Klebsiella
What are 2nd generation cephalosporins used for? (E.g. Cefaclor, Cefuroxime)
G(+) COCCI => less than 1st gen
MSSA
RODS
Bacteroides fragilis (anaerobes)
What are 3rd generation cephalosporins used for? (E.g. Cefdinir, Ceftriaxone)
Expanded g(-) RODS (E.colis, klebsiella)
good G(+) cocci — ceftriaxone
moderate pseudonomas
Ceftriaxone –» N. gonorrhoeae
What are adverse rxns associated w/ cephalosporins?
- Generally well-tolerated due to high toxicity
1) Allergy/hypersensitivity: anaphylaxis, rashes, nephritis
2) GI distress: nausea, vomiting, diarrhea
3) Superinfection w/ 2nd and 3rd gen
4) Can intensify anticoag warfarin! w/2nd gen
What is the mechanism of action for Vancomycin?
- Stage 2: cell wall synthesis inhibition
- Blocks glycopeptide elongation by binding to D-alanyl-D-alanine part of cell wall precursor
Bactericidal
Which bacteria are shown to be resistant to Vancomycin?
S. Aureus (VRSA)
Enterococci (VRE)
B/c these bacteria do not have a D-ala-D-ala peptide
Describe the absorption of Vancomysin
bad PO
IV use!
How is vancomycin excreted from the body?
Via the kidneys
Remember dosage adjustment may be needed w/ renal probs
What is vancomysin used for?
G(+) Cocci => S. aureus, Staph, Strep, Entero
Anaerobes => C. Diff (but metronidazole is first choice…)
What are adverse rxns associated w/ Vancomycin?
- Usually related to dosing and/or route of admin
1) Chills, fever, rash
2) Nephrotoxicity
3) Ototoxicity
Describe the mechanism of action for carbapenems
- STAGE 3: CW synthesis inhibitor
- Beta-lactamase resistant
How are carbapenems administered?
Parenterally (IV only)
Describe the distribution of carbapenems
Good into CSF
How are carbapenems excreted?
Via kidneys
increase t1/2 if renal failure
What are carbapenems used for?
- Reserved for multiple drug resistant organisms
- Used when aminoglycosides and cephalosporins don’t work
G(-) rods G(+) cocci Pseudomonas C perf MSSA, not MRSA
What are the adverse rxns associated w/ carbapenems?
N/v, diarrhea, rash
Seizures, rarely
