Agents Targeting Cell Wall (Gartenberg) Flashcards
Bacterial Cell Wall Drugs
- penicillins
- ß-lactamase inhibitors
- cephalosporins
- monobactams
- carbapenems
- glycopeptides
- lipopeptides
- defensins
- inhibitors of peptidoglycan precursors
transglyosylase & transpeptidase
transglycosylase combines NAG/NAM monomers in peptidoglycan, transpeptidase cross-links
ß-lactam antibiotics (mechanism, families (4))
-ex penicillin: mimic D-ala D-ala part of cross-link, irreversibly bind transpeptidase, preventing proper crosslinking, cell lysis (bactericidal). But only works vs growing bacteria!!
4 families:
- Penicillin (5-member ring)
- cephalosporins (6-member ring)
- carbapenem (5-member ring)
- monobactam (no ring)
ß-lactamases (mechanism)
-many gram - bacteria possess. Altered transpeptidase that can reversibly bind ß-lactams, allowing them to stay active
ß-lactamase inhibitor (mechanism, exs)
- bulky ß-lactam that irreversibly binds ß-lactamases
- given with regular ß-lactam antibiotic in combination to allow it to work again
- ex: clavulinic acid, tazobactam, sulbactam
Avibactam (drug class)
- broad spectrum ß-lactamase inhibitor
- given with 3rd gen. cephalosporin (ceftazidine)
Penicillin G (class, target bacteria)
Common penicillin, good vs. gram +/- cocci, anaerobes, anything else that doesn’t produce ß-lactamase. Acid labile (broken down by stomach acid)
Oxacillin, Cloxacillin, Dicloxacillin (class, features, target bacteria, non-target bacteria)
Acid-stable, ß-lactamase resistant penicillins.
- good vs. ß-lactamase staph, penicillin-susceptible strep and pneumococci
- NOT GOOD vs enterococci, gram - rods/cocci, anaerobes
Amoxicillin
Acid stable, extended spectrum penicillin. Good vs. gram -.
- ß-lactamase susceptible, so combo with ßLI (Augmentin = clavulanic acid + amoxicillin)
- Used for sinusitis, UTIs, LRT, otitis.
Penicillins (route of administration, clearance time, side effects, allergy replacement)
- given oral, IV
- 3-4 hour clearance, so multiple dose/day
- little side effects, but rash, diarrhea, nausea
- if allergy, all penicillins. Give 2nd gen.+ cephalosporins instead
Cephalosporins (route, elimination, uses
-oral/IV
-kidney elimination, dont give to renal insufficient
-used vs. sinusitis, otitis, LRT. 4th gen. vs. MRSA
-can have hypersensitivity reactions- anaphylaxis, fever, skin rash, nephritis, granulocytopenia, hemolytic anemia
-
Cefazolin (class, spectrum, special use)
1st gen. cephalosporin
- broad spectrum, better vs. gram +
- used prophylactically in surgery
- no CNS penetration
Cefamandole (class, spectrum, special use)
2nd gen. cephalosporin
- broad spectrum like 1st gen., improved gram - activity
- no cross-reactive allergy with penicillin, so used as replacement
Ceftazidime (class, spectrum, special use)
3rd gen. cephalosporin
- improved gram - but weakened gram + activity
- not effective alone against constitutive ßL
- Avycaz: ceftazidime + ßLI (avibactam)
Cefepime (class, spectrum, special use)
4th gen. cephalosporin
- broadest spectrum cephalosporin, vs gram +/- good
- penetrates CNS
- used vs p. aeruginosa, haemophilus, enterobactericiae, s. aureus, s. pneumoniae, nesseria, penicillin-resistant streptococci
Ceftolozane (class, spectrum, special use)
5th gen. cephalosporin
- used vs. resistant gram - bacteria like pseudomones, complicated UTIs or intrabdominal
- Given with tazobactam (ßLI) to extend half life
Ceftaroline/ceftobiprole
cephalosporins for MRSA (late gen.)
- given IV
- broad spectrum
Monobactams (class, special property, spectrum, ex)
- resistant to ß-lactamases
- active vs. gram - rods (like pseudomones, serratia)
- no activity vs. gram +
- given IV, no cross reaction with penicillin, no side effects
- ex: aztreonam
Carbapenems (class, spectrum, use, side effects)
- broad spectrum, used for mixed infections
- resistant vs. serine ß-lactamases
- penetrate CNS, excreted renally
- cross react with penicillin
- side effects: vomiting, diarrhea, skin rash, penicillin allergy
Imipenem
Carbapenem, inactivated in renal tubules
Cilastatin
Improves half life of carbanepems by inhibiting renal dehydropeptidase
Meropenem
carbapenem, resistant to renal dehydropeptidase so better half life
Vancomycin (class, spectrum, mechanism, side effects)
glycopeptide
-active vs. gram +, especially staph
-bactericidal vs growing cells: binds peptidoglycan unit, preventing proper incorporation, weakening wall and lysis
-resistance via D-ala D-ala–>D-ala D-lactic acid
-penetrates CNS
-used in combo with aminoglycosides vs. enterococci
side effects: minor (phlebitis, chills, fever, nephrotoxicity, ototoxicity)
-given IV, oral for enterococci
-other glycopeptides: teicoplanin, televancin
Dalbavancin (class, use, spectrum)
derivative of teicoplanin (glycopeptide)
- good as vancomycin but less frequent dosing (2x week)
- Good for skin infections of MDR gram +
