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PR3151 Antibiotics + Antifungals > Cell wall synthesis inhibitors > Flashcards

Cell wall synthesis inhibitors Flashcards

1
Q

Cell wall inhibitors are all ________

A

Bactericidal

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2
Q

Cell wall inhibitors generally have ______ CSF penetration

A

Good

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3
Q

B lactams bind to transpeptidase and interfere with cross-linking of the terminal peptide components of the linear polymer chains. This results in?

A

Weakening of cell wall structure, build up in intracellular osmotic pressure, bacterial cell lysis

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4
Q

4-membered B-lactam fused to ____-membered ring in ____?

A

5 membered ring => penicillins and carbapenems

6-membered dihydrothiazine ring => cephalosporins

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5
Q

Penicillinase is an enzyme that degrades penicillin by __________

A

Hydrolyzing cyclic amide bond in the B lactam ring, thereby inactivating the antibiotic

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6
Q

Penicillinase resistant penicillins and aminopenicillins can be given _____

A

Penicillinase resistant penicillins: oral/IV/IM

Aminopenicillins: oral/IV

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7
Q

Cloxacillin (penicillinase resistant penicillins) covers only _____ and ______

A

MSSA and Streptococcus

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8
Q

Why do penicillinase resistant penicillins have protection against penicillinase?

A

They have bulky side groups that limit accessibility of B-lactamase

This also explains their narrow spectrum of activity (MSSA and Streptococcus)

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9
Q

Why do aminopenicillins have greater coverage (gram-negative in addition to gram-positive)?

A

Aminopenicillins have hydrophilic groups that allow penetration into gram-negative bacteria via porins in the outer membrane

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10
Q

Aminopenicillins has gram-negative coverage against hemophilus influenzae and E coli. It does NOT cover _____ and _____

A

Does NOT cover pseudomonas aeruginosa and klebsiella

*if in combi with BLI, can cover proteus and klebsiella

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11
Q

Incomplete oral absorption of ampicillin results in higher incidence of ____

A

Diarrhea

*Amoxicillin has better oral absorption than ampicillin

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12
Q

Gram-negative coverage of piperacillin-tazobactam includes _______, ________ and _______

A

Pseudomonas, Klebsiella, Proteus, H. influenzae, E coli

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13
Q

Why might probenecid be used with penicillins?

A

To prolong penicillin’s effect since probenecid inhibits tubular secretion of penicillin

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14
Q

Hypersensitivity due to penicillins is due to _____

A

Penicilloic acid (degradation pdt of penicillin), that acts as a hapten

=> combines with host proteins to form adducts that stimulate Ab pdn

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15
Q

Penicillins and Carbapenems (but also all B lactams) can cause ______ when ___________________________

Patients with _____ have higher risk

A

Cause neurotoxicity when blood levels of the antibiotics are elevated

*Confusion, hallucination, seizures

Pt with renal failure have higher risk

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16
Q

What are some penicillins that may cause hepatotoxicity?

A

Oxacillin, nafcillin, flucloxacillin, augmentin

17
Q

Apart from production of B-lactamases in MSSA, and altered transpeptidase to PBP2a in MRSA, what are two other mechanisms of resistance to penicillins?

A
  1. Downregulation of porin expression, decreased ability of antibiotic to reach PBP
  2. Presence of efflux pumps
18
Q

How do B-lactamase inhibitors work?

A

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

19
Q

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.

A

Bacteroide fragilis (anaerobic)

Metronidazole, Carbapenems, Clindamycin, Moxifloxacin

20
Q

Cephalosporins have broadened anti-bacterial spectrum due to:

A
  1. Increased affinity for transpeptidases
  2. Increased ability to penetrate gram-negative cell wall
  3. Increased resistance to beta-lactamase
21
Q

What do (1st to 5th gen) cephalosporins lack activity against?

A

Listeria
Atypicals
MRSA (except 5th gen)
Enterococcus

ESBL-producing strains
Bacteroides

22
Q

What are some gram-negatives that (1st to 5th gen) cephalosporins can cover?

A

E coli, Klebsiella, Proteus, Haemophilis influenzae

Only ceftazidime, cefepime, and ceftobiprole covers pseudomonas

23
Q

Ceftriaxone should not be mixed or reconstituted with ______

A

Calcium containing pdts (e.g., Ringer’s or Hartmann’s solution) as it will cause calcium precipitates

24
Q

Which cephalosporin lacks gram positive coverage?

A

Ceftazidime
*It does not cover MSSA and streps

25
Q

Carbapenems are first line against _________.

Name 2 other drugs that have activity against this as well

A

ESBL-producing gram-negative bacteria (e.g., ESBL producing E coli, Klebsiella)

Aminoglycosides, Tigecycline

26
Q

Ertapenem lacks activity against _______ and ________

A

Pseudomonas and Enterococcus

27
Q

Can Aztreonam be used to treat ESBL producing stains?

A

No

28
Q

Can Aztreonam be used against Bacteroides?

A

No, they don’t have anaerobic coverage

29
Q

Aztreonam is generally well-tolerated, but may cause occasional ______ and ______

A

skin rash and transaminasemia

30
Q

Aztreonam can have cross-reactivity to _____

A

Ceftazidime

31
Q

Vancomycin is ineffective against gram-negative due to _____

A

large molecular size (1500kDa), unable to penetrate outer membrane of gram negatives

32
Q

Oral Vancomycin can be used to treat ____

Name the only other drug that can treat this as well

A

CDAD

Metronidazole

33
Q

Name the adverse effects of Vancomycin

A

Nephrotoxicity
Ototoxicity
Red man syndrome (+ hypotension)

34
Q

Explain how Enterococcal resistance and S. aureus resistance against Vancomycin emerged.

A

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

35
Q

Which penicillin does not achieve therapeutic levels of penetration into CSF?

A

Penicillinase resistant penicillins

PR3151 Antibiotics + Antifungals (5 decks)

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