Antibiotics II

Question 1

What are 4 common methods of AB resistance?

Answer 1

1. Decreased permeability of cell
2. Alteration of target site
3. Enzyme inactivation
4. Efflux of drug

Question 2

To what protein do penicillins bind to exert their effect?

Answer 2

Penicillin binding protein

Question 3

What is the structural difference b/w Gram (+) and Gram (-) organisms?

Answer 3

Gram (+) cells have a rigid cell wall made of peptidoglycan layers while Gram (-) cells have a multilayered cell wall that contains lipopolysaccharide (LPS)

Question 4

Where is the site of bacterial hydrolysis of penicillins that lead to resistance?

Answer 4

Hydrolysis of the Beta lactam ring with beta lactamase

Question 5

Describe the mechanism of beta lactamase resistance

Answer 5

Beta-lactamase breaks down beta lactam ring of penicillins, cephalosporins, monobactams, and carbepenems and therefore the drugs cannot bind to the penicillin binding protein

Question 6

Describe the mechanism of cancomycin resistance involving cell walls

Answer 6

1. The peptidoglycans of the cell wall acquire a terminal lactate and therefore vancomycin cannot bind
2. OR the cell wall of the bug can become so thick that the vancomycin gets caught and cannot exert its effect

Question 7

What is an important resistance mechanism that all Staphylococcus aureus has acquired?

Answer 7

Penicillinase! All SA is penicillin reisistant

Question 8

What are the two most common penicillin binding proteins?

Answer 8

PBP2b and PBP2x

Question 9

What drugs bind to PBP2b?

Answer 9

Penicillins and first generation cephalosporins

Question 10

What drugs bind to PBP2x

Answer 10

All non-first generation cephalosporins, the carbapenms, and monobactams

Question 11

What is the bacterial function of PBP?

Answer 11

Anchor and orient the native bacterial transpeptidase which is required to cross-link cell walls

Question 12

What type of mutation would confer resistance to all lactam drugs?

Answer 12

Concurrent alterations in PBP2b and PBP2x would confer resistance to all lactam ABs

Question 13

What characteristic of lactams make them very susceptible to hydrolysis

Answer 13

High-tension 90 degree angle bond

Question 14

Are carbepenems susceptible to penicillinase?

Answer 14

No because carbepenems are not penicillins

Question 15

What are the two ways to protect penicillins from hydrolysis?

Answer 15

1. Adding bulky aromatic groups around the ring to sterically inhibit penicillinase
2. Combine penicillins with suicide inhibitor from the clavam class of drugs

Question 16

Why are neither penicillins nor cephalosporins effective against Extended spectrum beta lactamase gram negative species?

Answer 16

These bugs produce an abundance of of lactamase

Question 17

What is the typical presentation from a lactam-induced allergy?

Answer 17

Either anaphylaxis (hives, angioedema, respiratory stridor, hypotension) or Maculo (flat/red)-papular (lumpy/bumpy) skin eruption

Question 18

What is a serious allergic complication of lactams?

Answer 18

Interstitial nephritis, toxic epidermal necrolysis, cytopenia)

Question 19

What is the antigenic focux responsible for essentially all cases of drug allergy to lactams?

Answer 19

5/6 member ring adjacent to lactam ring

Question 20

What is the cause of allergic cross reactivity b/w penicillins and cephalosporins?

Answer 20

The similarity b/w the functional groups b/w penicillins and cephalosporins at R1 position

Question 21

What immune reaction causes the maculopapular rash from aminopenicillins?

Answer 21

Antigenic reaction with an IgM Ab (NOT IgE) and occurs in 100% of patiets with acute infectious mononucleosis from EBV

Question 22

What are the lactam drugs?

Answer 22

Penicillins, Cephalosporins, carbepenems, monobactam

Question 23

What are the penicillins?

Answer 23

• penicillin g, penicillin v
• penicillinase-resistanat penicillins [oxacillin, dicoxacillin]
• Amniopenicillins [ampicillin, amoxicillin]
• Extended spectrum penicillins [piperacillin]
• Penicillins w/ suicide inhibitors [Piperacillin-tazobactam, amoxicillin-clavulanate]

Question 24

What are the Cephalosporins?

Answer 24

• First generation [cefazolin, cephalexin]
• Second generation [cefuroxime]
• Third generation [ceftriaxone and ceftazidime, cefpodoxime]