2 - Antimicrobials I Flashcards

1
Q

Technically speaking, what’s the difference between an antibiotic and an antimicrobial?

A

An Antibiotic technically has to be a chemical produced by a microbe that has the ability to harm other microbes

Antibiotics like sulfonamides, which are produced in a lab and are not made by other organisms, are antimicrobials but not technically antibiotics

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2
Q

What differences between mammalian and bacterial cells make selective toxicity possible?

A
  1. Bacteria are encased in a rigid cell wall, and the osmotic pressure within the bacterium is extremely high. Since mammalian cells don’t have cell walls, we can give drugs that effect cell walls without worrying about host effects
  2. Mammals obtain folic acid from nutrition, but bacterial cells have to synthesize folic acid for themselves. Sulfonamides block the conversion of PABA into folic acid, which kills microbes but doesn’t effect mammalian cells
  3. Bacterial cells and mammalian cells have very different ribosomes. We can impair bacterial ribosomes without effecting mammalian ones
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3
Q

For most drugs, where is the site of action?

Why is this important?

A

Intracellular

Microbes can develop resistance by controlling what comes in and out of the membrane. They can cease active uptake of certain drugs, and increase active export of others, reducing the effectiveness of the drug

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4
Q

Which bacterial gene codes for almost complete resist to almost all bacteria?

A

New Delhi metallo-beta-lactamase 1 (NDM-1)

pg. 654

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5
Q

There’s only two ways that bacteria can develop resistance:

A

by mutating spontaneously

by conjugating (transferring extrachromosomal DNA from one bacteria to another)

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6
Q

What is an R-Factor?

A

The elements needed for conjugation

In order to transfer resistance by conjugation, the donor organism has to have two unique DNA segments:

  1. The codes for mechanisms of drug resistance
  2. the codes for the sexual apparatus required for DNA factor

The two DNA segments make up the R-Factor

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7
Q

Conjugation takes place primarily among ______ bacteria

A

Gram negative

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8
Q

Is conjugation species specific?

A

NO!

Pathogenic bacteria can inherit R factors from other pathogens or even the normal flora of the body

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9
Q

Which mechanism for resistance usually causes multiple drug resistance?

A

Conjugation

In a single event, a drug-sensitive bacterium can become highly drug resistant

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10
Q

How do different species of microbes in the body keep each other in check?

A
  1. They secrete compounds that are toxic to other microbes
  2. They compete with each other for available nutrients
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11
Q

Which antibiotics promote resistance

A

ALL OF THEM

BUT broad spectrums facilitate emergence the most

Resistance is created by killing, so the more bacteria a drug kills, the more likely it is to create resistance

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12
Q

Obviously antibiotics promote emergence of resistant pathogens. But what else do they promote?

A

Resistant normal flora

this is a big problem because they flora can conjugate with pathogens and create resistant pathogens

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13
Q

What is a superinfection?

Give an example

A

a NEW infection that appears during the course of treatment for a different infection

Getting a yeast infection after taking a drug for a UTI

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14
Q

Hospital acquired pneumonias are usually caused by which three pathogens?

A

Pseudomonas species

Klebsiella species

Staph Aureus

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15
Q

What is a PCR?

A

Polymerase Chain Reaction

An enzyme is used to generate thousands of copies of DNA/RNA unique to the infecting microbe, creating enough material for detection

MORE SPECIFIC AND MORE SENSITIVE THAN GRAM STAINING

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16
Q

To be effective, an antibiotic must be present at the site of infection in a concentration greater than:

A

the minimal inhibitory concentration (MIC)

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17
Q

Why do bacteria flourish on foreign hardware?

A

Phagocytes are too busy attacking the organism to attack the bacteria, allowing microbes to flourish

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18
Q

There is one disease in which the use of multiple drugs actually prevents resistance:

A

TB

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19
Q

As a rule, postop antibiotics are _______

A

unnecessary

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20
Q

There are four types of surgery in which ABX prophylaxis is proven necessary:

A
  1. Cardiac
  2. Vascular
  3. Orthopedic
  4. GI
21
Q

Why are penicillins so wonderful?

A

Broad Spectrum

Low Toxicity

22
Q

Penicillin MOA

A

Weakens the Cell Wall:

  1. Disrupts the cell wall. Inhibits transpeptidases, enzymes critical to the cross bridges that form a strong cell wall
  2. Promotes active destruction of the cell wall. Activates Autolysins, enzymes that cleave bonds in the cell wall
23
Q

The molecular targets of the penicillins are collectively known as:

A

Penicillin-binding proteins (PBPs)

24
Q

Where are PBPs located?

A
25
Q

Do penicillins penetrate Gram negative cells?

A

Generally, no. The can penetrate cell walls, but not the outer membranes that gram negative bacteria have

Only ampicillin

26
Q

What are Beta lactamases?

A

enzymes that cleave the beta lactam ring

The beta lactam ring is the part that binds with PBPs, so the antibiotic is rendered inactive

27
Q

To date, no known strains of S. Aureus produce Beta lactamases capable of inactivating methicillin. So why do we have MRSA?

A

Methicillin-resistant S. Aureus produce PBPs with a low affinity for PCNs and other Beta Lactams.

Completely different method of resistance than Beta Lactamases

28
Q

What is the least toxic of all antibiotics?

A

Penicillin G

29
Q

Can someone who is allergic to a penicillin receive a cephalosporin?

A

Depends on the severity of the reaction

Only 1% of people with a PCN allergy react to cephalosporins, so if the have a rash or something it’s fine. If they had anaphylaxis, it’s not

30
Q

What part of penicillin causes allergic reactions?

A

HAPTENS!

Byproducts of penicillin bind with a protein, forming a hapten and THAT’s what forms an antigen for antibody formation

31
Q

What is the principle difference between Penicillin V and Penicillin G?

A

V can survive in stomach acid

G cannot

32
Q

There are two broad spectrum penicillins:

A

Ampicillin

Amoxicillin

They have all the normal gram positive abilities, but also are active against some gram negative bacilli

33
Q

Which side effects occur more frequently with ampicillin that with any other penicillin?

A

Rash and Diarrhea

34
Q

Why are cephalosporins so popular?

A

Broad Spectrum

Often resistant to Beta lactamases

Low toxicity

35
Q

What is the Cephalosporin MOA?

A

Same as PCN:

Cell wall synthesis and autolysins

36
Q

Which generations of cephalosporins are sensitive to Beta Lactamases?

A

Got smarter over time.

1st: destroyed
2nd: less sensitive

3th/4th/5th: Highly resistant

37
Q

How are cephalosporins absorbed?

A

Generally have to be IM or IV

38
Q

Which cephalosporins interact with alcohol like antabuse?

A

Cefazolin

Cefotetan

39
Q

Which cephalosporin is associated with bleeding?

A

Cefazolin, Cefotetan, ceftriaxone

40
Q

There is only one fifth generation cephalosporin. What is it used for?

A

Ceftaroline

Gram Positive, particularly MRSA

41
Q

Which carbapenems are active against MRSA?

A

None of them

42
Q

How are carbapenems absorbed

A

Poorly. Always given IV.

43
Q

Which carbapenem has an extremely broad spectrum?

A

Imipenem

44
Q

Which antibiotic is most effective against anaerobic bacteria?

A

Imipenem

45
Q

Which patients should absolutely not be placed on imipenem?

A

Anyone using valproate

Reduces blood levels of valproate, causing breakthrough seizures

46
Q

What is the MOA of Vancomycin?

A

inhibits cell wall synthesis

BUT

It does NOT interact with PBPs! It disrupts the cell wall by binding to molecules that serve as precursors for cell wall biosynthesis

47
Q

Vancomycin is only active against ________ bacteria

A

Gram Positive

48
Q

C. Diff is Gram _______

A

positive

49
Q

Which ABX are most likely to promote C. Diff?

A

Clindamycin

2nd and 3rd generation Cephalosporins

Fluoroquinolones (Cipro, Levaquin)