Cell wall synthesis inhibitors Flashcards
Cell wall inhibitors are all ________
Bactericidal
Cell wall inhibitors generally have ______ CSF penetration
Good
B lactams bind to transpeptidase and interfere with cross-linking of the terminal peptide components of the linear polymer chains. This results in?
Weakening of cell wall structure, build up in intracellular osmotic pressure, bacterial cell lysis
4-membered B-lactam fused to ____-membered ring in ____?
5 membered ring => penicillins and carbapenems
6-membered dihydrothiazine ring => cephalosporins
Penicillinase is an enzyme that degrades penicillin by __________
Hydrolyzing cyclic amide bond in the B lactam ring, thereby inactivating the antibiotic
Penicillinase resistant penicillins and aminopenicillins can be given _____
Penicillinase resistant penicillins: oral/IV/IM
Aminopenicillins: oral/IV
Cloxacillin (penicillinase resistant penicillins) covers only _____ and ______
MSSA and Streptococcus
Why do penicillinase resistant penicillins have protection against penicillinase?
They have bulky side groups that limit accessibility of B-lactamase
This also explains their narrow spectrum of activity (MSSA and Streptococcus)
Why do aminopenicillins have greater coverage (gram-negative in addition to gram-positive)?
Aminopenicillins have hydrophilic groups that allow penetration into gram-negative bacteria via porins in the outer membrane
Aminopenicillins has gram-negative coverage against hemophilus influenzae and E coli. It does NOT cover _____ and _____
Does NOT cover pseudomonas aeruginosa and klebsiella
*if in combi with BLI, can cover proteus and klebsiella
Incomplete oral absorption of ampicillin results in higher incidence of ____
Diarrhea
*Amoxicillin has better oral absorption than ampicillin
Gram-negative coverage of piperacillin-tazobactam includes _______, ________ and _______
Pseudomonas, Klebsiella, Proteus, H. influenzae, E coli
Why might probenecid be used with penicillins?
To prolong penicillin’s effect since probenecid inhibits tubular secretion of penicillin
Hypersensitivity due to penicillins is due to _____
Penicilloic acid (degradation pdt of penicillin), that acts as a hapten
=> combines with host proteins to form adducts that stimulate Ab pdn
Penicillins and Carbapenems (but also all B lactams) can cause ______ when ___________________________
Patients with _____ have higher risk
Cause neurotoxicity when blood levels of the antibiotics are elevated
*Confusion, hallucination, seizures
Pt with renal failure have higher risk
What are some penicillins that may cause hepatotoxicity?
Oxacillin, nafcillin, flucloxacillin, augmentin
Apart from production of B-lactamases in MSSA, and altered transpeptidase to PBP2a in MRSA, what are two other mechanisms of resistance to penicillins?
- Downregulation of porin expression, decreased ability of antibiotic to reach PBP
- Presence of efflux pumps
How do B-lactamase inhibitors work?
Clavulanic acid: suicide inhibitor, covalently bind to B-lactamase and restructures it, permanently inhibiting it
Sulbactam and tazobactam: binds to or near active site irreversibly
Apart from additional coverage against MSSA and gram-negative aerobes, Beta-lactam/BLI also extends cover for ________
Name 4 other agents that can cover this as well.
Bacteroide fragilis (anaerobic)
Metronidazole, Carbapenems, Clindamycin, Moxifloxacin
Cephalosporins have broadened anti-bacterial spectrum due to:
- Increased affinity for transpeptidases
- Increased ability to penetrate gram-negative cell wall
- Increased resistance to beta-lactamase
What do (1st to 5th gen) cephalosporins lack activity against?
Listeria
Atypicals
MRSA (except 5th gen)
Enterococcus
ESBL-producing strains
Bacteroides
What are some gram-negatives that (1st to 5th gen) cephalosporins can cover?
E coli, Klebsiella, Proteus, Haemophilis influenzae
Only ceftazidime, cefepime, and ceftobiprole covers pseudomonas
Ceftriaxone should not be mixed or reconstituted with ______
Calcium containing pdts (e.g., Ringer’s or Hartmann’s solution) as it will cause calcium precipitates
Which cephalosporin lacks gram positive coverage?
Ceftazidime
*It does not cover MSSA and streps
Carbapenems are first line against _________.
Name 2 other drugs that have activity against this as well
ESBL-producing gram-negative bacteria (e.g., ESBL producing E coli, Klebsiella)
Aminoglycosides, Tigecycline
Ertapenem lacks activity against _______ and ________
Pseudomonas and Enterococcus
Can Aztreonam be used to treat ESBL producing stains?
No
Can Aztreonam be used against Bacteroides?
No, they don’t have anaerobic coverage
Aztreonam is generally well-tolerated, but may cause occasional ______ and ______
skin rash and transaminasemia
Aztreonam can have cross-reactivity to _____
Ceftazidime
Vancomycin is ineffective against gram-negative due to _____
large molecular size (1500kDa), unable to penetrate outer membrane of gram negatives
Oral Vancomycin can be used to treat ____
Name the only other drug that can treat this as well
CDAD
Metronidazole
Name the adverse effects of Vancomycin
Nephrotoxicity
Ototoxicity
Red man syndrome (+ hypotension)
Explain how Enterococcal resistance and S. aureus resistance against Vancomycin emerged.
VRE: expression of enzymes that modify the cell wall precursor by substituting the D-alanine for D-lactate or D-serine, therefore reducing binding affinity of vancomycin
VRSA: reduced susceptibility of bacteria to vancomycin
Which penicillin does not achieve therapeutic levels of penetration into CSF?
Penicillinase resistant penicillins
