Antimicrobials 1

Question 1

Three broad types

Answer 1

Antibiotics
- bacterial

Antivirals
- viral

Antimicotics
- fungal

Question 2

Prophylactic therapy

Answer 2

A sort of “pre-treatment” used in immunosuppressive patients that help increase resistance/treatment of an infection

Question 3

Empiric vs definitive therapy

Answer 3

Empiric: agent is selected based on rational, often broad, judgements and experience

Definitive: agent is selected based on lab results and cultures with pathogen identity confirmed.

Difference is definitive is more narrow spectrum and reduces risk of resistance emerging against broad spectrum agents.
- also reduces super/opportunistic infections as well as community resistance

Question 4

Most common gram negative rods

Answer 4

Enterobacters

E. coli

Haemophilus influenza

Proteus

Pseudomonas aeruginosa

Question 5

Prophylactic therapy

Answer 5

Is a pre-treatment to prevent infections in immunocompromised patients

Question 6

Empiric vs definitive therapy

Answer 6

Empiric (broad)= treatment of known or probable infection

Definitive (narrow)= pathogens identify and antibiotic susceptibility is 100% confirmed

• moving from an empiric to definitive therapy reduces risks of resistance development and reduces risk of superinfections/opportunistic infections*

Question 7

Classes of antibiotics for bacterial infections

Answer 7

Inhibitors of cell wall synthesis

Inhibitors of protein synthesis

Inhibitors of DNA/RNA synthesis

Question 8

General mechanisms of cell wall inhibitors that affect PBPs

Answer 8

All are bacterialcidal via 2 actions

• transpeptidase inhibition: cant synthesis new walls
• autolysin activation: break down cell walls too fast

Both autolysin and transpeptidase are penicillin binding proteins (PBPs) and are found on both gram positive and gram negative bacteria

penicillin has no effect on host cells since human cells do not possess cell walls or PBPs

Question 9

Cell wall synthesis inhibitors broad mechanisms with respect to synthesis of peptidoglycan

Answer 9

Three main steps are possible

1) inhibition of synthesis of the Murein monomers
2) inhibition of polymerization of murein monomers into Glycan backbone
3) inhibition of glycan polymer cross-linking into peptidoglycan (transpeptidases)
* B-lactams prevents the cross linking, the rest of the cell wall synthesis inhibitors do everything else*

Question 10

Peptidoglycan wall components

Answer 10

Primarily N-Ag and N-Am proteins

Question 11

Why are cell wall synthesis inhibitors far more effective towards gram positive vs gram negative bacteria?

Answer 11

Gram positive possess more peptidoglycan than negative

Gram negative possess an additional outer membrane that blocks peptidoglycan

• cell wall inhibitors require gram negative bacteria to possess porin channels in order to infect them*

Question 12

Mechanisms of resistance to cell wall inhibitors by bacteria

Answer 12

Altered PBPs

Expression of efflux pumps

development of B-lactamase enzymes that function to cleave B-lactam drugs

Question 13

How all B-lactams are common

Answer 13

They all possess a common core structure

“active component” ring (3 carbons and 1 nitrogen)

These ring components acetylate PBPs and inactivates them in bacteria

Question 14

B-lactamases

Answer 14

Defend bacteria against B-lactams
- primarily penicillins and cephalosporins

• B-lactamases inhibitors exist = clavulanic acid/clavulanate, sulbactam, tazobactam and avibactam*

Also some chemical modifications to B-lactams can make them more resistant to the B-lactamases (I.e methicillin)

Question 15

DDIs for penicillin

Answer 15

Anti-gout medications (probalan specifically)

-blocks renal transporters

Question 16

Aminopenicillins

Answer 16

Ampicillin (IV) and amoxicillin (PO)

• amoxicillin is drug of choice for upper respiratory infections*
• can develop resistance via B-lactamases*

Question 17

What is the only antipseudomonal penicillin usable?

Answer 17

Piperacillin

• renally eliminated and specifically targets pseudomonas, kiebsiella pneumoniae
• do NOT co-administrate with vancomycin (increases acute intestinal nephritis risk)*
• high doses causes poor coagulation*

Question 18

Cephalosporins

Answer 18

B-lactam drugs that are often used against bacteria that use penicillinase (cant use penicillin on them)

5 generations exist with varying spectrums

Question 19

1st generation cephalosporins

Answer 19

Cefazolin (IV)

Cephalexin (PO)

Cefadroxil (PO)

Similar to anti-staph penicillins but are better tolerated
- great against MSSA, step species, staph species that have penicillinase

DONT USE AGAINST MRSA

Are renally excreted

Question 20

Second gen cephalosporins

Answer 20

Cefactor (PO)

cefuroxime (PO)

Cefoxitin (IV)

Usually used against organisms that can be affected by 1st gen, but also includes more gram negative rods and cocci

• never inject via IM*

Are renally excreted

Question 21

3rd gen cephalosporins

Answer 21

Cefotaxime (IV/IM)

Ceftazidime (IV/IM)

Ceftriaxone (IV/IM)

Often used against hamophilus and pneumococci infections and gonorrhoeae infections
- better against gram (-) than (+)

enter the CSF

Renal excretion except for ceftriaxone (liver excretion)

Question 22

Why are there generations of cephalosporins

Answer 22

A lot of bacteria have grown resistance to previous generations

• also newer generations tend to have more gram(-) activity compared to gram (+) activity*
• exception is gen 5 ceftaroline (anti-MRSA)

Question 23

Which 1st gen cephalosporin drug penetrates BBB?

Answer 23

Cefazolin (IV)

- drug of choice for surgical prophylaxis and bacteria staph infections

Question 24

What drug combo is used for resistant intra-abdominal/urinary tract infections?

Answer 24

Ceftazidime and avibactam

Question 25

4th gen cephalosporins

Answer 25

Cefepime (IV) Only major drug and has similar uses to 3rd generation except for it also is indicated for the following - enterobacter infections - Lyme disease - encephalopathy - P. Aeruginosa Renally cleared *distributes well into the CSF*

Question 26

5th gen cephalosporins

Answer 26

Ceftaroline (IV) Binds to mutated PBP that confers resistance to almost all other b-lactams *can be used as an absolute final decision for almost all bacterial infections especially complicated ones, however it is used almost exclusively for only MRSA*

Question 27

Aztreonam

Answer 27

Primary used monobactams - non penicillin; non cephalosporin narrow spectrum that only works against gram negative bacteria - similar spectrum to 3rd gen - highly resistant to B-lactamases Used primarily to treat serious gram (-) infections and for patients who are allergic to penicillin/ cephalosporins *can not be crossed with patients who are allergic to ceftazidime (can develop cross-allergenicity to aztreonam)* Can penetrate BBB

Question 28

Carbapenems

Answer 28

Imipenem/cilastatin Doripenem Ertapenem Meropenem Renally excreted and all administered via IV Broad spectrum agents used for patients who are experiencing resistant infections and are allergic to penicillin - Urinary tract infections - lower respiratory infections - intra-abdominal and vaginal infections * dont use for pseudomonas infections*

Question 29

Why is imipenem always used with cilastatin clinically?

Answer 29

Imipenem by itself will be hydrolyzed to a toxic metabolite in the proximal tubular epithelium by renal dipeptidase - cilastatin is an adjunct agent that prevents renal dipeptidase form doing this

Question 30

Glycopeptides

Answer 30

Include primarily vancomycin and teicoplanin MOA is to inhibit cell wall synthesis by preventing glycan strand polymerization - also inhibit transpeptidase (PBP) Primarily used for gram-positive infections (stap/strep) that are resistant to penicillin/cephalosporins. * PO form is only used against c.diff infections*

Question 31

Glycopeptides ADRs

Answer 31

Pretty widespread but are reversible - phlebitis - ototoxicity - nephrotoxicity - “red man syndrome” via hypersensitivity * treat this with antihistamines and stop usage*

Question 32

Worst misdiagnosis you can make as it pertains to antibiotics

Answer 32

Prescribing a patient who has a viral infection antibiotics. (doesn’t do anything and increases chance of developing resistance, even higher chance if the antibiotic you prescribe is a broad/empiric agent)