Intro to anti-microbials

Question 1

What is selective toxicity?

Answer 1

Most ideal drug will be highly selective against the bugs that are causing the most problem and still causes little toxicity to the host

Need to target something that’s common among bacteria and are specific to bacteria

Question 2

A good antibiotic should have a high/low therapeutic index?

What is the spectrum of activity?

Answer 2

High

Spectrum of activity

Each antibiotic takes adv of a particular target. Each agent has microbes that it has activity against and some for which it is useless

Question 3

Describe the difference between a broad spectrum agent and a narrow spectrum agent

When would you use either?

Answer 3

A broad spectrum agent has activity against multiple different bacteria, a narrow spectrum antibiotic is a little bit more targeted

The more narrow spectrum an agent is, the less adverse effects, the less likely it is to develop resistance and is ass’d with fewer allergies/HSRs

Broad spectrum: Useful when you don’t know the organism that’s the cause of infection, if pt has infection with more than one bug or in the case of antibiotic resistance

Narrow spectrum: useful when causative agent is known

Question 4

What is the difference between intrinsic and acquired anti-microbial resistance?

Answer 4

Intrinsic: depend on the target. Some antibiotics target the cell membrane for example and if a bacterium don’t have that particular component in the membrane that your drug targets, the drug is not going to work

Acquired: transfer of resistance genes or thru mutations

Question 5

What are 5 other mechanisms that bacteria employ to develop resistance to antibiotics?

Answer 5

Some bacteria can pump the antibiotic out (avoid it – pump it out), render it ineffective by inactivating it (inactivate it – break it or stick something to it), evolving to live with the antibiotic by changing its target, or avoiding it (don’t let it in)

Question 6

Describe the difference between bacteriostatic and bacteriocidal

Answer 6

Bacteriocidal agents are those that kill bacteria whereas bacteriostatic ones are ones that inhibit growth

Need to consider which drug to use (static vs cidal) depending on the situation, for example: infections that are difficult to treat because the bug is sequestered (e.g. if the bug is behind the blood brain barrier or in bone tissue or heart tissue or anywhere else where antibiotics can’t reach easily)

Question 7

Which antibiotics are associated with the development of C. diff infection?

Answer 7

All antibiotics are ass’d with development of C. diff

Question 8

What 3 antibiotics are the most commonly reported for C. diff infection?

Answer 8

Fluoroquinolones

Cephalosporins

Clindamycin

(Fluorian was about to quin dating this girl Clinda (clindamycin) coz she was getting spores in her cephal and she always had C.diff!- not a good look)

Question 9

Two types of drugs that inhibit Folic acid metabolism are __ and __

Answer 9

Trimethroprim and sulfonamides

(Prim took meth 3x and she’s already addicted to sulfas. That’s unfortunate coz now she can’t make folic acid)

Question 10

The combination drug that works to inhibit folic acid synthesis (and thus amino acid synthesis) is ___

Answer 10

Trimethoprim-Sulfamethoxazole

Question 11

Trimethoprim-Sulfamethoxazole has two parts to its function. One part is the inhibition of the 1st part of folate synthesis which is conducted by the (sulfa/trimethroprim) part of the antibiotic. What is the 2nd enzyme in the folate synthesis pathway that this antibiotic inhibits?

Answer 11

Trimethoprim-Sulfamethoxazole has two parts to its function. One part is the inhibition of the 1st part of folate synthesis which is conducted by the sulfa part of the antibiotic.

The sulfa part of the drug>> mimics PABA and competes with it to competitively bind to dihydropteroate synthase (inhibits 1st step of folate synthesis) (the part that ends with a synthase = sulfa)

Trimethoprim is a potent inhibitor of dihydrofolate reductase (note that humans also have this enzyme but the drug has a greater affinity for the bacterial version of the enzyme)

Question 12

T/F: Trimethroprim sulfas have a broad range of activity including working against anaerobes

Answer 12

Falsehood. See image below

Question 13

In general, trimethroprim sulfas work against skin and soft tissue infections (e.g. community acquired MRSA). What 3 other cases are these drugs used for?

What 3 niche infections would you use these drugs for?

Answer 13

Respiratory infections

Urinary tract infections

Bacterial diarrhea

Nocardia (just another planet)

Stenotrophomonas maltophilia (maltophilia like you like those malts so much you gon get stenotrophomonas)

Pneumocystis jirovecii

Question 14

Common adverse effects of trimethroprim sulfas include ___

Less common adverse effects include ___

Severe adverse effects include ___

Answer 14

Rash, nausea/vomiting, headache

Less common effects: hyperkalemia, hepatitis, pancreatitis

Severe effects: Steven Johnson syndrome (and hemolytic anemia in people with G6PD deficiency)

Question 15

Trimethroprim sulfas can also cause kidney issues. How?

What is kerniterus and how do thes drugs cause this?

Answer 15

Trimethorprim acts to decrease the tubular secretion of creatine and thus causes elevated serum creatine; this elevation, however, does not reflect a true reduction in glomerular filtration rate and true nephrotoxicity is rare (although can occur).

Kernicterus: babies are born with yellowing in the skin and eyes because of elevated levels of bilirubin in the blood. The drug binds albumin which decreases free albumin, leading to unconjugated bilirubin in the blood

Question 16

A 21-year-old woman complains of 2 days of dysuria, urinary frequency and urgency. She is diagnosed with symptomatic urinary tract infection and is given a prescription for trimethoprim-sulfamethoxazole. Which of the following adverse effects is most likely to occur?

a. Headache
b. Nausea
c. Maculo-papular rash
d. Overgrowth of resistant microorganisms
e. Pseudomembranous colitis

Answer 16

Answer = D, Overgrowth of resistant microorganisms

As discussed overgrowth of resistant microorganisms is a side effect of every antibiotic and can occur with a single dose

While trimethorpim-sulfamethoxazole can commonly cause headache, nausea, and rash the effect on the microbiome resulting in selection and overgrowth of resistant microorganisms is the most likely adverse effect.

Question 17

A 38-year-old healthy man presents to clinic with a skin and soft tissue infection of the right lower leg (cellulitis); he is not toxic appearing and vital signs are normal. Which of the properties would be “ideal” in an antibiotic agent?

A.Intravenous administration

B.Spectrum of activity covering GI microorganisms

C.Very broad spectrum

D.Low therapeutic index

E.Oral administration, high bioavailability

Answer 17

Answer = E, oral administration and high bioavailability

This otherwise healthy man with few/no comorbidities and a mild severity of illness should be managed at home with oral antibiotics; intravenous antibiotics would not be appropriate because that would require hospitalization which is otherwise unnecessary. The agent selected does not need to be “very broad spectrum” in this case and can be more directed to organisms common to the site of infection (i.e. skin and soft tissue); coverage of GI pathogens would not be appropriate. It is never desirable to have a low therapeutic index

Question 18

A 38-year-old man with diabetes presents to clinic with a skin and soft tissue infection of the right lower leg (cellulitis); he is confused, toxic appearing and hypotensive. Which of the properties would “ideal” in an antibiotic agent?

A.Narrow spectrum

B.Spectrum of activity covering GI microorganisms

C.Very broad spectrum

D.Low therapeutic index

E.Oral administration, high bioavailability

Answer 18

Answer = C, very broad spectrum

This patient is very ill and while the responsible organisms may be suspected based on the patients signs and symptoms of a skin and soft tissue infection at this point the organisms remain unknown, furthermore he has risk factors (e.g. diabetes) for more severe or unusual infections. In this case, a broad (not narrow) spectrum antimicrobial agent(s) would be appropriate until the causative microorganism is identified. Oral administration, even with high bioavailability, is not preferable/ideal. Coverage of GI pathogens is not appropriate since this is not the most likely source of infection. A low therapeutic index is never desirable.