Week 3 - Intro to Antibiotics

Question 1

Antimicrobial encompasses

Answer 1

Antibacterial, antifungal, antiparasitic, antiviral

Question 2

Selective Toxicity

Answer 2

Antibiotics need to injure the invading organism while causing minimal adverse effects to the host

Question 3

What is major target of antibiotics?

Answer 3

Cell wall - There is no cell wall in humans so it wont affect us! Antibiotics can damage cell wall and render bacteria damaged, killing them

Question 4

Toxicity of antibiotics

Answer 4

• Extension of mechanism of action.
  ex. Trimethoprim can inhibit folate metabolism in humans resulting in bone-marrow suppression…
• Unintended consequences
  ex. Vancomycin can stimulate histamine release resulting in red man syndrome

Question 5

Therapudic index

Answer 5

High therapeutic index means fewer adverse reactions (cell wall inhibitors)

Question 6

What does trimethoprim inhibit? (extension of mechanism action)

Answer 6

Folate metabolism in humans resulting in bone-marrow suppression

Question 7

What does vancomycin stimulate? (Unintended consequence)

Answer 7

Release of histamines resulting in red man syndrome..

Question 8

Spectrum of Activity

Answer 8

Spectrum of antibiotics

Narrow - Gram negative cocci

Extended - Gram negative rods and cocci

Broad - Many gram positive and gram negative organisms

Question 9

Narrow spectrum antibiotics target?

Answer 9

Gram negative cocci

Question 10

Extended spectrum antibiotics target?

Answer 10

Gram negative rods and cocci

Question 11

Broad spectrum antibiotics target?

Answer 11

Many gram positive and gram negative organisms

Question 12

Prophylaxis Therapy

Answer 12

Treating infections that has not yet developed but is at a high risk of developing an infection

Question 13

Pre-emptive Therapy

Answer 13

Lab test that shows infection but no symptoms are showing yet. The advantage is that it decreases amount of antibiotics used

Question 14

Empiric Therapy

Answer 14

Take culture, patient has infection with serious potential consequences but the organism has not been identified (broad spectrum). Example meningitis

Question 15

Definitive Therapy

Answer 15

Pathogen identified (mono therapy, narrow spectrum)

Question 16

Suppressive Therapy

Answer 16

After initial disease is controlled, therapy is continued at a lower dose

Question 17

Which of the following situations describes empiric antibiotic therapy?

A. Beginning nitrofurantoin for a patient with a history of repeated urinary tract infections to prevent another infection

B. Beginning nitrofurantoin for a patient with signs and symptoms of a urinary tract infection with a positive urinalysis

C. Beginning nitrofurantoin for a patient with signs and symptoms of a urinary tract infection with E. coli growing in the urine that are susceptible to nitrofurantoin

D. Beginning nitrofurantoin for a patient with signs and symptoms of a urinary tract infection with E. coli growing in the urine that are resistant to nitrofurantoin

Answer 17

B

Question 18

Pharmacokinetics

Answer 18

Body’s effect on a drug - must treat the individual with the right drug, right dose, right route, and right duration to kill ENOUGH bacteria to elimiate the infection (Rely on immune system to kill remaining)

Question 19

What are the 4 R’s of a drug?

Answer 19

Must treat the individual with right drug, right dose, right route, and right duration to kill enough bacteria to eliminate the infection

Question 20

Absorption of drug

Answer 20

movement of drug into vascular system

Question 21

Distribution of a drug

Answer 21

transfer of drug from intravascular to extravasular blood brain barrier presents a challenge

Question 22

Metabolism of a drug

Answer 22

irreversible transformation of parent compound into daughter metabolites often in the liver

Question 23

Excretion of drug

Answer 23

elimination of the drug from the body through urine or feces

Question 24

Drug-drug interaction

Answer 24

drug interactions often occur when one drug inhibits or induces the uptake or
clearance of another drug

Question 25

Types of drug administration

Answer 25

Oral, IV, IM, SQ, Inhalant, SL, Intrathecal (into CSF fluid - to brain), rectal, or topical

Question 26

6-year old patient presents to you in clinic with a high fever and inflamed throat. The mother is asking for antibiotics. What will you do?

Answer 26

Check to see if it is bacterial! Responsible writing of prescriptions is important since: 1. Need to minimize the development of antibiotic resistant microorganisms 2. Minimize harm to the patient caused by toxicity due to the use of an unnecessary or inappropriate drug. 3. Provide cost effective treatment. Hospital purchases of antibiotics usually represent 25-30% of the drug budget.

Question 27

Rapid strep test is...

Answer 27

A positive rapid antigen detection test is diagnostic specific (\>95%) available in minutes but sensitivity is (80-90%) Serologic test- characteristic proteins or polysaccharides are detected with antibodies May have a false negative or infection could be due to another bacterial organism

Question 28

Lateral Flow Assay Architecture

Answer 28

draw it. Going to see how fast the material moves through the strip.. the test line will get stuck to RED carbohydrates and you can see a positive strip..

Question 29

Gram Stain and Morphologic Analysis

Answer 29

Used if rapid strep test is negative... takes 24-48 hours then do **gram stain and morphologic analysis**. Look for structure (chain vs cluster) (cocci vs bacilli)

Question 30

Biochemical Tests

Answer 30

Catalase, coagulase test, hemolysis, glucose/lactose fermentation

Question 31

Catalase Test

Answer 31

monitors degradation of H2O2; differentiates between staphylococci (present) and streptococci (absent)

Question 32

Coagulase Test

Answer 32

differentiates Staphylococcus strains

Question 33

Hemolysis Test

Answer 33

clearing around colonies on a blood agar plate differentiates between streptococci α-hemolytic form green ring β-hemolytic clearing around colonies on agar plates γ-hemolysis no hemolysis

Question 34

Glucose/lactose fermentation test

Answer 34

Can distinguish bacteria by their metabolic properties

Question 35

Throat Culture Q From your patient’s throat culture, you get back the following images for the Gram stain and growth on blood agar.You identify the bacteria as ... Streptococcus pyogenes Streptococcus pneumoniae Staphlococcus aereus Staphlococcus epidermis Neisserria meningitidis Need a consult

Answer 35

Gram positive. Streptoccoccus (long chain) B is a diplococci.. This is beta hydrolysis.. Then use dichotimous key to determine it is A.

Question 36

Use John Hopkin's guide to identify the appropriate antibiotic for treatment of Group A streptococcal infection and consider what factors will effect which antibiotic you choose

Answer 36

Pregnancy, cost, administration, patient (kid vs adult) etc

Question 37

What classes of drugs have many allergies?

Answer 37

Beta-lactams (penicillin) and sulfonamides etc... In some cases, allergy to a particular drug will predict allergies to other drugs in the class. Must be careful about labeling a patient as allergic since this can result in treatment with inferior drugs Can do a skin test to confirm and try penicillin desensitization.

Question 38

What can be done to confirm a penicillin allergy?

Answer 38

Skin test

Question 39

Age of pt important. Why?

Answer 39

In elderly pts, kidney function is reduced.. With decreases excretion...

Question 40

Does pt have any other diseases?

Answer 40

ex. Chloramphenicol is inactivated by liver metabolism. With impaired liver function, dose should be reduced.

Question 41

Bacteriostatic

Answer 41

Limits growth and if removed the organism can grow again... Usually successful because it allows immune system to catch back up

Question 42

Bactericidal

Answer 42

Kills 99.9% of bacterial reduction in bacterial inoculums within a 24 hour period. Attacks cell well, disfiguring it and altering osmotic barrier. Bacterial cells lyse.

Question 43

What happens when antibiotics are administered to bacteria that are not actively dividing?

Answer 43

Wont work. Some drugs can be baceriostatic against one organism and bactericidal against another

Question 44

Plot of number of viable bacteria vs Time If your patient was undergoing cancer chemotherapy and had a suppressed immune system, would you choose drug A or drug B to treat the infecting organism? Why?

Answer 44

draw it. Drug B is bactericidal, Use drug B for ppl who are immunocompramized\*

Question 45

Are there genetic factors that make pt susceptible to toxic side effects? (ex?)

Answer 45

Yes. Sufonamides - may cause hemolysis of RBCs in pts with G6P dehydrogenase deficiency

Question 46

Is the pt pregnant?

Answer 46

Important. Look on Johns Hopkins guide of ABx to find risk. Look at table 1... B is really not a risk. 1st trimester is most critical usually.. some drugs may be safe in 3rd semester but not 1st..

Question 47

Has the pt recently been on an antibiotic?

Answer 47

Confirm correct organism. Think drug resistance or super infection

Question 48

Drug resistance

Answer 48

Increased elimination, Drug-interacting enzymes, decreased uptake, alteration in target molecule

Question 49

Superinfection

Answer 49

Consequences of overly broad antibiotic treatment... The balance of the normal residents of the bowel, skin, etc. is maintained by competition for nutrients and the production by bacteria of compounds that inhibit the growth of other bacteria. When an antibiotic kills an important resident bacterium, other harmful bacteria may be able to multiply and cause a secondary infection or superinfection. The broader the spectrum of activity and the longer time period of antibiotic treatment, the more likely that treatment with the antibiotic will cause superinfection. Symptoms of superinfection range from mild diarrhea to acute enteritis.

Question 50

Intrinsic Resistance

Answer 50

Is an absence of inaccessibility of the target for the drug reaction. Ex mycoplasma lack cell walls so they are intrinsically resistant to cell wall inhibitors. No change in the genetics of the bacteria occurs..

Question 51

Acquired Drug Resistance What is very important to understand?

Answer 51

Bacteria change their DNA (mutation) OR acquire new DNA resulting in resistance to a drug \*VERY IMPORTANT to understand that the drug itself is not causing the resistance

Question 52

What is very important about drug resistance?

Answer 52

The drug itself is NOT causing the resistance

Question 53

DNA-mediated transformation

Answer 53

Look at picture. after replication. 1 daughter cell will be resistant, one won't.. the one with the resistance then will start increaseing more rapidly. Transformation

Question 54

Bacteriophage can introduce new DNA through transduction

Answer 54

look at picture. Transduction

Question 55

Ways of drug resistance

Answer 55

Transformation, transduction, conjucation, transposition

Question 56

Conjugation

Answer 56

transfer of R plasmid may contain several resistance determinant genes common amongst gram NEG. look at video of this..

Question 57

Transposition

Answer 57

Can then cause the movement of genetic material within the genome

Question 58

How is antibiotic resistance transferred from Enteroccoccus to Staphylococcus?

Answer 58

Look at pic...think MRSA

Question 59

Few new antibiotics are being developed..

Answer 59

..more and more organisms are becoming resistant

Question 60

Antibiotic Susceptibility Testing

Answer 60

Results can be at least as important as determining the etiologic agent... some organisms

Question 61

Minimum Inhibitory Concentration (MIC)

Answer 61

Lowest concentration of antibiotic that prevents visible growth in culture, ug/ml

Question 62

What is MIC Breakpoint?

Answer 62

lk

Question 63

If MIC is lower than breakpoint...

Answer 63

er

Question 64

What is advantage of agar testing vs broth testing?

Answer 64

Contamination and heterogenous populations are more obvious. Agar is preferred...

Question 65

Phenotypic test

Answer 65

Looking at outcome of growth in presence of antibiotic

Question 66

Genotypic test

Answer 66

Look at actual genes.. look this up. Can look up if gene is resistant..

Question 67

12 Steps to prevent antimicrobial resistance

Answer 67

Look at picture

Question 68

What happens if a pt does not take full course of antibiotics?

Answer 68

..the antibiotics dont work as well after they are stopped becasue the first few doses will kill the MOST susceptible bacteria.. the more resistant form will still be there to reproduce..not there are tougher bacteria to try and get rid of.

Question 69

What ways can we form a mutualistic partnership with bacteria?

Answer 69

Use antibiotics in a way that limits harm to microbiome..

Question 70

NBME Q

Answer 70

c diff.