Cell wall synthesis inhibitors

Question 1

Cell wall inhibitors are all ________

Answer 1

Bactericidal

Question 2

Cell wall inhibitors generally have ______ CSF penetration

Answer 2

Good

Question 3

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

Answer 3

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

Question 4

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

Answer 4

5 membered ring => penicillins and carbapenems

6-membered dihydrothiazine ring => cephalosporins

Question 5

Penicillinase is an enzyme that degrades penicillin by __________

Answer 5

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

Question 6

Penicillinase resistant penicillins and aminopenicillins can be given _____

Answer 6

Penicillinase resistant penicillins: oral/IV/IM

Aminopenicillins: oral/IV

Question 7

Cloxacillin (penicillinase resistant penicillins) covers only _____ and ______

Answer 7

MSSA and Streptococcus

Question 8

Why do penicillinase resistant penicillins have protection against penicillinase?

Answer 8

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

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

Question 9

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

Answer 9

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

Question 10

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

Answer 10

Does NOT cover pseudomonas aeruginosa and klebsiella

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

Question 11

Incomplete oral absorption of ampicillin results in higher incidence of ____

Answer 11

Diarrhea

*Amoxicillin has better oral absorption than ampicillin

Question 12

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

Answer 12

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

Question 13

Why might probenecid be used with penicillins?

Answer 13

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

Question 14

Hypersensitivity due to penicillins is due to _____

Answer 14

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

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

Question 15

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

Patients with _____ have higher risk

Answer 15

Cause neurotoxicity when blood levels of the antibiotics are elevated

*Confusion, hallucination, seizures

Pt with renal failure have higher risk

Question 16

What are some penicillins that may cause hepatotoxicity?

Answer 16

Oxacillin, nafcillin, flucloxacillin, augmentin

Question 17

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

Answer 17

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

Question 18

How do B-lactamase inhibitors work?

Answer 18

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

Question 19

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.

Answer 19

Bacteroide fragilis (anaerobic)

Metronidazole, Carbapenems, Clindamycin, Moxifloxacin

Question 20

Cephalosporins have broadened anti-bacterial spectrum due to:

Answer 20

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

Question 21

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

Answer 21

Listeria
Atypicals
MRSA (except 5th gen)
Enterococcus

ESBL-producing strains
Bacteroides

Question 22

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

Answer 22

E coli, Klebsiella, Proteus, Haemophilis influenzae

Only ceftazidime, cefepime, and ceftobiprole covers pseudomonas

Question 23

Ceftriaxone should not be mixed or reconstituted with ______

Answer 23

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

Question 24

Which cephalosporin lacks gram positive coverage?

Answer 24

Ceftazidime
*It does not cover MSSA and streps

Question 25

Carbapenems are first line against _________. Name 2 other drugs that have activity against this as well

Answer 25

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

Question 26

Ertapenem lacks activity against _______ and ________

Answer 26

Pseudomonas and Enterococcus

Question 27

Can Aztreonam be used to treat ESBL producing stains?

Answer 27

No

Question 28

Can Aztreonam be used against Bacteroides?

Answer 28

No, they don't have anaerobic coverage

Question 29

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

Answer 29

skin rash and transaminasemia

Question 30

Aztreonam can have cross-reactivity to _____

Answer 30

Ceftazidime

Question 31

Vancomycin is ineffective against gram-negative due to _____

Answer 31

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

Question 32

Oral Vancomycin can be used to treat ____ Name the only other drug that can treat this as well

Answer 32

CDAD Metronidazole

Question 33

Name the adverse effects of Vancomycin

Answer 33

Nephrotoxicity Ototoxicity Red man syndrome (+ hypotension)

Question 34

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

Answer 34

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

Question 35

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

Answer 35

Penicillinase resistant penicillins