Antimicrobials Dr. Roane

Question 1

3 major ways bacteria are pathogenic

Answer 1

1. multiply and disturb normal processes - clog airway, biofilm disturbing drug delivery
2. toxin (Shiga toxin, botulinum toxin)
3. overreaction of the immune system -> toxic shock

Question 2

How to treat ESBLs (extended-spectrum beta-lactamases)

Answer 2

Cefamycin
Cephalosporin

Question 3

How to treat ampC bacteria

Answer 3

resistant to Cephamycins and Cephalosporin
Carbapenem

Question 4

MOVIE QUESTIONS!!!

Question 5

What does antibiotic stewardship mean?

Answer 5

Improving antibiotic prescribing and use

Question 6

What does coverage mean?

Answer 6

Range of bacteria that can be treated
f.e. Oxacillin covers Staph infections but not MRSABacteriocidal

Question 7

Overuse of antibiotics

Answer 7

-Handsoap
-animal feed
-doctors office, health care facilities

Question 8

Where are antibiotics derived from?

Answer 8

Plant or microbial origin
-using fighting mechanism of plants and microbes

Question 9

Differences of antibiotics

Answer 9

-Physical (Formulation)
-Chemical (beta-lactam, tetracycline - 4cycles)
-Pharmacologic (MOA, metabolism, distribution)
-Antibacterial spectra - (which organisms are susceptible)

Question 10

Bacteriostatic VS Bacteriocidal

Answer 10

Bacteriostatic: Prevent multiplication or growth
-> may not be effective in immunocompromised patients

Bacteriocidal: Kill bacteria

Question 11

How is Communibility or Transmissibility measured?

Answer 11

Ro (R naught) -> the higher the more transmissible

Question 12

Pathogenicity, Virulence and Resistance

Answer 12

-Pathogenicity: the ability of an organism to cause a
disease

-Virulence: how harmful is it

a pathogen can cause disease (athlete’s foot) without being very harmful (virulent)

-Resistance: a pathogen is not treatable

Question 13

What are the different MOA of antibiotics?

Answer 13

-Inhibition of cell wall synthesis
- Cell wall disruption
-Ribosome binders (30S and 50S) inhibit protein synthesis
-Inhibitors of bacterial gene expression
- Metabolism inhibitors

Question 14

How can tuberculosis (Mycobacteria) be treated?

Answer 14

Isoniazid (narrow-spectrum antibiotic)
-> can pretty much only treat tuberculosis

Question 15

The spectrum of Ampicillin?

Answer 15

Gram (+) bacilli
Gram (-) rods

Question 16

The spectrum of Tetracyclin?

Answer 16

Very broad: Chlamydia, Mycoplasma, Spirochetes, Anaerobics, Gram (-) rods

Question 17

Pregnancy Categories

Answer 17

A: No human risk or fetal harm
B: No controlled studies with human risk, animal studies show potential toxicity
C: Animal toxicity, for human undefined

D: Human fetal risk, but benefits outweigh (mother could die)

X: Contraindicated in pregnancy

Question 18

How can MIC and MBC be measured?

Answer 18

Grow bacteria in antibiotics with increasing concentration -> Once it stops showing growth you have your MIC

Subculture the bacteria in fresh media -> at a lower concentration, there is growth again bc the antibiotics were thrown away and the bacteria grew back again (bacteriostatic)-> but on higher concentration vials there was no growth bc all the bacteria were killed (bactericidal)

Question 19

What factors determine the susceptibility of a pathogen?

Answer 19

-Local factors: pH, protein level (drug might bind to a protein on site), low blood perfusion, Biofilm, Abscesses

-Urin concentration of a drug is sometimes higher than in plasma -> organism could be more susceptible in the urine than in the respiratory system

Question 20

How do bacteria gain resistance?

Answer 20

-beta-lactamase (breaks ß-lactam ring)
-Altered target molecule -> the molecule that the drug binds to has changed (MRSA - ß lactam doesn’t bind anymore)
-Porin (polar channel) proteins altered - drug can’t get in
-Transporters become mutated - drug cant enter
-Overproduction of efflux pumps
-Bacteria don’t activate the prodrug anymore: Isoniazid and Mycobacterium tuberculosis

Question 21

How do bacteria share resistance among each other?

Answer 21

-Conjugation (horizontal transfer) through Plasmids (containing genes coding for resistance proteins)

Question 22

How else can bacteria obtain resistance?

Answer 22

-Mutation
-Transduction: Bacteriophage injecting foreign DNA
-Transformation: Uptake of environmental DNA

Question 23

How does Staph aureus fight Penicillins?

Answer 23

ß-lactamase
-> treated with Methicillin

Question 24

How does Staph aureus fight Methicillin?

Answer 24

altering the binding site of Methicillin
-> treated with Vancomycin (now we start seeing resistant bacteria VMRSA)
-Alternatives: Ceftaroline, Tigecycline or Linezolid

Question 25

Difference between a chromosomal-mediated and a plasma-mediated resistance

Answer 25

The chromosomal-mediated resistance is gained by mutations and is not shared between bacteria, and it is less frequent than plasma-mediated resistance

Question 26

What makes plasma-related resistance clinically important?

Answer 26

-occurs in different species (especially gram neg rods)
-resistance to multiple drugs
-high rate of transfer (by conjugation)
-resistance is constitutive (always active, chromosomal-mediated resistance is often activated slower once the drug is present)

Question 27

What are the different ß-lactamases?

Answer 27

-Penicillinases (Penicillin 5-membered ring)
-Cephalosporinase (Cephalosporin 6 membered)

-ESBL (extended spectrum beta-lactamases)
-ampC (resistance to Cephalosporins and cephamycins + not blocked by ß-lactamase inhibitors)

-Carbapenemase (Carbapene is used late in the hierarchy)
KPC (Klebsiella pneumonia carbapenemase)
NDM-1 (“New Dehli” metalloenzymes – require zinc for activity)
CRE (Carbapenem resistant enterobacteriaceae)

Question 28

Combination of antibiotics

Answer 28

-sulfamethoxazole and Trimethoprim -> SYNERGY (inhibit the same pathway)
-Clavulinic acid and amoxicillin (Augmentin), Imipenem/cilastatin

-Penicillin (fast growth) and chlortetracycline (slow growth) for meningitis -> antagonistic

Question 29

What is Concentration-dependent killing?

Answer 29

-more drug means faster killing

-for some drugs, there is no significant increase of killing with an increase in drug concentration

Question 30

What is Empiric therapy?

Answer 30

-Prescriber does not know the identity of the
infectious agent -> and makes the best guess

Question 31

What is a Superinfection?

Answer 31

-occurs with antibiotic therapy (higher risk with bride-broad antibiotics)

-the proliferation of certain spp. (less affected by the drug) of intestinal flora

-Clostridium difficile (C. diff) superinfection (colon disease - can be fatal)