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FDN3 Minnie > Antibiotics/Vaccines > Flashcards

Antibiotics/Vaccines Flashcards

1
Q

Which vaccine prevents Ebolavirus?

A

A monoclonal antibody vaccine is in development

Recombinant viral vector derived from VZV

It protects against Ebola Zaire

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2
Q

What does T > MIC represent in a time-concentration curve?

A

The fraction fo the dosing interval for which the drug concentration remains above the MIC

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3
Q

What are the “Four Core Actions” that are recommended by the CDC for combating antibiotic resistance?

A
  • Prevent infections/spread of infections
  • Track resistance patterns
  • Improve the use of antibiotics
    • Practice good stewardship; use only when necessary, use narrowest spectrum and shortest duration that is appropriate
  • Develop new antibiotics and diagnostic tests
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4
Q

How can you use MIC and MIC breakpoint to choose the best antibiotic against a particular agent?

A

You want to choose the antibiotic with the MIC furthest below the MIC breakpoint

This is especially importatn for very sick patients and multi-drug resistant strains

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5
Q

Which PK/PD parameters are unique to antibiotics (as opposed to other drugs)?

A

T>MIC

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6
Q

What kind of vaccine is the measles vaccine?

A

Live attenuated vaccine

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7
Q

Which beta-lactam would be safest to give to a patient with a penicillin allergy?

A

Aztreonam

The side chain is structurally different from other beta-lactams

(Still use extreme caution if the patient has an anaphylactic reaction)

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8
Q

Which beta-lactam antibiotic is not active against gram-positive bacteria?

A

Monobactam (Aztreonam)

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9
Q

What kind of antibiotic is trimethoprim/sulfamethoxazole?

A

A sulfonamide

Sulfonamides inhibit the folate synthesis pathway, this inhibiting bacterial DNA synthesis

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10
Q

Which toxicity is most commonly associated with aminoglycosides?

A

Neprotoxicity

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11
Q

What is the difference between empiric and directed antibiotic therapy?

A

Empiric therapy is based on clinical judgement and reasoning

  • You have done your best to narrow down the causative agent of disease based on presentation and symptoms
  • You choose an antibiotic that will be active against the most likely causes

Directed therapy is informed by cell culture and lab results

  • You know exactly which bacteria you need to kill
  • You choose an antibiotic active against that bacteria
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12
Q

In general, which antibiotics are bacteriostatic?

Are there exceptions?

A

In general, agents that inhibit protein synthesis are bacteriostatic

Exception: Aminoglycosides inhibit protein synthesis but are bactericidal

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13
Q

Are anti-staphylococcal penicillins active against MRSA?

Why or why not?

A

Anti-staphylococcal penicillins are not active against MRSA

  • MRSA is resistant to all penicillins becaue it possesses an alternative PBP, called PBP 2a
  • Even penicillins that are not destoryed by beta-lactamase cannot bind to PBP 2a, therefore they will not kill MRSA
  • To treat MRSA, use vancomycin, clindamycin (but confirm susceptibility with D-test), trimethoprim-sulfamethoxazole, linezolid, or daptomycin
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14
Q

What are the dosing recommendations for concentration-dependent antibiotics?

A

Goal = highest possible peak concentration (CMax)

  • Duration of peak and T>MIC have no impact on efficacy
  • Give high doses less frequently
    • Low troughs are okay
      • Reduces the risk of toxicity
      • Microbes are still killed due to post-antibiotic effect
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15
Q

What kind of vaccine is the HiB vaccine?

Why is it important?

A

The HiB vaccine protects against Haemophilus influenzae, the former leading cause of childhood bacterial meningitis

Vaccination has basically eradicated the H. influenzae as a cause of bacterial meningitis :D

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16
Q

What is a broad spectrum antibiotic?

Give some examples

A

A broad-spectrum antibiotic is active against a variety of both gram (+) and gram (-) species

  • Beta-lactam/beta-lactamase inhibitors
    • Ampicillin/sulbactam
    • Piperacillin/tazobactam
  • Aminopenicillins
    • Amoxicillin
    • Ampicillin
  • Trimethoprim/sulfamethoxazole
  • Carbapenems
    • Imipenem
    • Meropenem
    • Doripenem
    • Ertapenem
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17
Q

Which antibiotic covers all of the most probable causes of community-acquired pneumonia?

A

Macrolides (azythromycin, erythromyin, clarithromycin)

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18
Q

What is the general mechanism of rifampin antibiotics?

A

Rifampin antibiotics inhibit RNA polymerase

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19
Q

What are the mechanisms of resistance of fluoroquinolone antibiotics?

A
  • Point mutations in the target enzyme (topoisomerase II or topoisomerase IV)
    • Prevents binding between fluoroquinolone and enzyme
  • Reducing the penetration of fluoroquinolone into the bacterial cell by removing porin channels or acquiring pumps to promote antibiotic efflux
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20
Q

Which fluoroquinolone antibiotic would you use against community-acquired pneumonia?

A

Moxifloxacin or levofloxacin (the respiratory fluoroquinolones

Ciprofloxacin is not active against streptococus pneumoniae (or other gram-positive bacteria), and therefore would not be a good choice

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21
Q

What are the two options for flu vaccination?

How are they different?

A
  • Trivalent inactivated subunit vaccine (TIV)
    • Intramuscular
    • Less effective (~50%-70%)
    • Fewer adverse effects
  • Live attenuated influenza vaccine (LAIV)
    • Intranasal
    • More effective especially in children (87%)
    • More likely to have adverse effects
      • URI symptoms in adults
      • Asthma flare in children
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22
Q

Describe the spectrum and clinical use of levofloxacin

A

Levofloxacin = respiratory fluoroquinolone

  • Spectrum
    • Gram positive
    • Gram negative
    • Pseudomonas
    • Atypical
  • Clinical use
    • Use against community-acquired pneumonia when streptococcus pneumoniae is suspected
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23
Q

Which toxicity is most commonly associated with Vancomycin?

A

Red Man’s Syndrome

Rash/pain during infusion due to release of histamine from mast cells

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24
Q

What is the general mechanism of glycopeptide antibiotics? (ex: vancomycin)

A

Inhibit cell-wall synthesis (at a different point than beta-lactams)

Binds D-alanyl-D-alanine, blocking the link to the glycopeptide polymer

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25
Q

List 3 commonly used fluoroquinolone antibiotics

A

Ciprofloxacin

Moxifloxacin (Respiratory)

Levofloxacin (Respiratory)

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26
Q

How is a C. diff treated?

A

Oral vancomycin = first choice

Metronidazole = alternative

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27
Q

Which penicillins are active against Staphylococcus spp?

Which are not?

A

Active against staph (not vulnerable to beta-lactamase)

  • Anti-staphylococcal penicillins (oxacillin)
  • Betalactam/beta-lactamase inhibitor combos
    • (Ampicillin/sulbactam, piperacillin/tazobactam)

Not active against staph (vulnerable to beta-lactamase)

  • Natural penicillin (panicillin V and G)
  • Aminopenicillins (ampicillin, amoxycillin)

Note: All penicillins have activity against Streptococcus spp.

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28
Q

What kind of antibiotic is amoxicillin-clavulanate?

A

Beta lactam + Beta lactamase inhibitor

Amoxicillin = beta lactam

Clavulanate = beta lactamase inhibitor

(Any -illin + something else is usually this combo)

This is prescribed to enhance activity against bacteria that synthesize beta-lactamase, such as MSSA and enterococci

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29
Q

What kind of antibiotics are -floxacins?

A

Fluoroquinolones;

They directly inhibit bacterial DNA synthesis

They are bactericidal

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30
Q

Give 1-2 examples of cephalosporins from each generation

A
  • 1st generation
    • Cefazolin
  • 2nd generation
    • Cefuroxime
  • 3rd generation
    • Ceftriaxone
    • Ceftazidime
  • 4th generation
    • Cefepime
    • Ceftaroline
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31
Q

What percentage of patients will have at least 1 adverse effect after taking antibiotics?

A

20%

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32
Q

What is the mechanism of resistance against vancomycin?

Which bacteria are likely to become resistant?

A

Vancomycin acts by binding to D-alanyl-D-alanine

Some enterococci and S. aureus spp possess the mobile genetic element vanAthat changes this target to D-alanyl-D-lactate or D-alanyl-D-serine basicallyruining the binding site for vancomycin

  • S. aureus may also be resistant due to an abnormally thick cell wall
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33
Q

Which antibiotics are time-dependent?

A

Aminoglycosides

Fluoroquinolones

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34
Q

Which beta-lactam antibiotic provides the most comprehensive gram-negative coverage?

A

Meropenem

(Cefepime, piperacillin/taxobactam, aztreonam, ceftazidime are also pretty good aginst most enterobacteriaceae and pseudomonas)

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35
Q

Which beta-lactams are most likley to cause a morbilliform rash?

A

Ampicillin and amoxicillin

Even more common if pt. also has EBV

Other beta-lactams are likely to be safe

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36
Q

Which toxicity is most commonly associated with Fluroquinolones?

A

Achilles tendon rupture

(Achilles tendon ruption is only associated with fluoroquinolones)

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37
Q

As a prescriber, what are 3 ways that you can prevent antibiotic resistance?

A
  • Only prescribe antibiotics when necessary
  • Use the narrowest spectrum antibiotic that is appropriate for the patient
  • Use the shortest duration that is appropriate for the patient
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38
Q

Which generation of cephalosporin is cefuroxime?

What is it active against?

A

2nd generation

  • Good gram (+) coverage
    • Strep and MSSA
  • Improved gram (-) coverage
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39
Q

Which cephalosporins have good gram positive coverage and the most limited gram negative coverage?

A

1st generation

Cefazolin

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40
Q

Compare the efficacy of conjugate vaccines with polysaccharide vaccines

A

Conjugate vaccines (polysaccharide conjugated to a peptide/protein) are more effective

The peptide is able to activate a cell-mediated immune resonse in addition to the humoral response activated by the polysaccharide

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41
Q

Which fluoroquinolone is not active against gram-positive bacteria?

A

Ciprofloxacin

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42
Q

Which fluoroquinolones are active against pseudomonas aeruginosa?

A

Ciprofloxacin and levofloxacin

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43
Q

In which clinical scenarios would it be important to use a bactericidal vs. a bacteriostatic agent?

A
  • If the patient is immune compromised
    • Their system will not be able to kill the bacteria
    • Young children, elderly patients, anyone else who is immunosuppressed
  • If the infection is serious
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44
Q

Describe the scope of antibiotic resistance in the USA

How many people are infected each year with an infection that is resistant to antibiotics?

How many die?

What is the economic cost?

A
  • How many people are infected each year with an infection that is resistant to antibiotics?
    • >2 million
  • How many die?
    • 23,000
  • What is the economic cost?
    • $20 billion in excess healthcare costs
    • An additional $35 billinon in lost productivity
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45
Q

Name two 3rd generation cephalosporins.

How are they different?

A

Ceftriaxone, ceftazidime

Ceftriaxone maintains some gram (+) activity

Ceftazidime does not have any gram (+) activity, and is active against pseudomonas

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46
Q

Which generation of cephalosporin is cefazolin?

What is it active against?

A

1st generation

  • Good gram (+) coverage
    • Strep, MSSA
  • Some gram (-) coverage
    • E. coli, K. pneumoniae, protius mirabilis
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47
Q

What is the minimum inhibitory concentration (MIC)?

A

The lowest concentration of an antibiotic that prevents visible growth of the organism after 18-24 hours of incubation

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48
Q

What is the general mechanism of lincosamide antibiotics?

A

Inhibit bacterial protein synthesis by binding the 50S subunit of bacterial ribosomes

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49
Q

What is the mechanism of tetracycline antibiotics?

A

Inhibit bacterial protein synthesis

Bind to the 30S bacterial ribosome

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50
Q

What does a live attenuated vaccine contain?

What is the efect on the host?

A

A weakened form of a live virus

  • (Virulence factors lost though multiple passages through subculture)
  • Must be able to replicate inside of the host in order to be effective
  • Immune response is similar to that of a natural infection without causing illness
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51
Q

What are the mechanisms of resistance to tetracycline antibiotics?

A
  • Protein pump acquisition/alteration
    • Impaired influx of antibiotic
    • Increased efflux of antibiotic
  • Proteins that interfere with tetracycline/ribosome binding
  • Enzyme inactivation
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52
Q

Which beta-lactam antibiotics provide the least gram-negative coverage?

A

Penicillin, oxacillin

(ampicillin only has minimal gram-negative activity)

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53
Q

What are the mechanisms of resistance of aminoglycoside antibiotics?

A
  • Bacteria produces transferase
    • Transferase inactivates the aminoglycoside via adenylation, acetylation, or phosphorylation
  • Reduce porin channels
    • Aminoglycoside cannot enter the bacterial cell
  • Mutations in the 30S subunit can prevent the aminoglycoside from binding to the ribosome
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54
Q

Which beta-lactam antibiotics are active against both gram-positive and gram-negative bacteria?

A
  • Anti-pseudomonal penicillins
    • Piperacillin
  • Beta-lactam/beta-lactamase inhibitor combos
    • Ampicillin/sulbactam
    • Piperacillin/tazobactam
  • Carbapenems
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55
Q

What is the mechanism of fluoroquinolone antibiotics?

A

Fluoroquinolones inhibit bacterial DNA synthesis by binding to the enzyme-DNA complex

  • Block topoisomerase II (aka DNA gyrase)
    • Prevents the relaxation of supercoils, blocking DNA replication
  • Block topoisomerase IV
    • Prevents the separation of replicated bacterial DNA into daughter cells
  • Bacteriostatic = fluoroquinolone binding to the enzyme-DNA complex
  • Bactericidal = complex cleaves DNA and prevents ligation
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56
Q

Which bacteria pose the most urgent threats (as per the CDC) for antibiotic resistance?

A

C. difficile

Carbapenem-resistant enterobacteriaceae (CRE)

Drug-resistant Neisseria gonorrhoeae

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57
Q

What kind of antibiotic is carbapenem?

A

A beta-lactam; interferes with peptidoglycan synthesis

Offers broad spectrum coverage; not vulnerable to beta-lactamases

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58
Q

Under which circumstances would you prescribe gentamicin for a patient with a staph infection?

A

Gentimicin (or any aminoglycoside) would only be prescribed in concert with another antibiotic class (ex: beta-lactam) to provide synergy if the infection is serious

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59
Q

What does it mean for an antibiotic to be “concentration-dependent?”

A

The antibiotic kills most effectively when the maximum concentration of the drug (CMax) is high

  • Duration of the peak does not matter
  • Typically has a post-antibiotic effect
    • Keeps killing even when concentration falls below MIC
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60
Q

What does it mean for an antibiotic to be “time-dependent?”

A

The antibiotic kills most effectively when the concentation of the antibiotic is above the MIC of the bacteria for as long as possible (T > MIC is large)

  • Magnitude of the peak is not important
  • May need to adjust dosing to avoid toxicity
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61
Q

What are 4 of the most common antibiotic toxicities shared by several classes of antibiotics?

A
  • Diarrhea
  • Anaphylaxis
  • Hepatotoxicity
  • Dermatological toxicity
    • Rash
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62
Q

Which two bacteria are the most likely causes of bacterial meningitis?

A

Streptococcus pneumoniae

Neisseria meningitidis

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63
Q

Which antibiotics act by inhibiting DNA synthesis?

A
  • Fluoroquinolones
    • Inhibit topoisomerase II and IV
    • (Ciprofloxacin, moxifloxacin, levofloxacin)
  • Sulfamethoxazole-trimethoprim
    • ​Inhibit bacterial folic acid synthesis pathway
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64
Q

Which infections can be treated with oxazolidinones (ex: linezolid)?

A

Many gram (+) bacteria

  • MRSA
  • MSSA
  • Streptococci
  • Enterococci (including vancomycin resistant)
  • Gram (+) anaerobic cocci
  • Gram (+) rods
65
Q

Is Dengvaxia (the vaccine for Dengue fever) recommended for everyone?

Why or why not?

A

Dengvaxia is only recommended for people who have had Dengue fever. It can protect against reinfection

In individuals who have not had Dengue fever, the vaccine increases the liklihood of death, should a person become infected wtih the vaccine. This is due to antibody-dependent enhancement of infection

66
Q

What is the general mechanism of sulfonamide antibiotics?

A

Inhibit the folic acid pathway

This inhibits bacterial DNA synthesis

67
Q

Describe the spectrum an clinical use of metronidazole

A
  • Spectrum
    • Anaerobic bacteria
      • Gram (+) cocci and bacilli (Clostridium)
      • Gram (-) bacilli (Bacteroides)
      • Protozoa (Trichomonas, giardiasis, amoebiasis)
  • Clinical use
    • Treat the above bacteria
    • Second choice agenta against C. diff**​
68
Q

Why is the HPV vaccine recommended for everyone?

A

It reduces cancer risk

Best to give before a person is sexually active; the vaccine does not work against established HPV infections (which people may have asymptomatically)

69
Q

List the arguments against double coverage antibiotic prescription

A
  • May promote antibiotic resistance
  • Increased cost
  • Increased potential for toxicity/adverse effects
  • Antagonism is possible
70
Q

What is the difference between Sabin’s and Salk’s poliovaccines?

Which one is given in the USA today?

A

Salk

  • Inactivated polio vaccine (IPV)
  • Virus is not live; cannot replicate in the body, will not cause polio
    • Except when it is manufactured poorly

Sabin

  • Live attenuated oral vaccine (OPV)
  • Virus is alive
  • Very effective and vaccinates many via fecal veneer
  • Has the potential to mutate and regain virulence; can cause vaccine-associated polio myelitis

In the United States, an enhanced-potency inactivated polio vaccine is used (A descendent of Salk’s vaccine)

71
Q

What are the dosing recommendations for time-dependent antibiotics?

A

Goal = 40%-50% of total time with [drug] above MIC (T>MIC)

  • Or longest duration of T>MIC possible (or maximize AUC/MIC?)
  • The magnitude of the peak (CMax) is not important
  • Dosing options (especially if MIC for the microbe is close to the MIC breakpoint of the antibiotic)
    • Lower the dose and increase the frequency
    • Extended infusion time
    • Continuous infusion
72
Q

What is the general mechanism of beta lactam antibiotics?

A

Beta lactam antibiotics inhibit bacterial wall synthesis by bindig to penicillin-binding proteins in the bacteria and interfereing with peptidoglycan formation

73
Q

List 3 aminoglycoside antibiotics

A

Gentamicin

Tobramycin

Amikacin

74
Q

Which anatomic compartments are considered “protected sites?”

How is this relevant to antibiotic treatment?

A

Protected sites are compartments that antibiotics do not readily perfuse; therefore, infections in these areas are hard to treat

  • CNS (Brain, CSF)
  • Eye
  • Prostate
  • Biofilms on prosthetic devices
75
Q

What is the difference between a Kirby-Bauer test and an E-test?

A
  • Kirby-Bauer = disks
    • Measure diameter of zone of inhibition
    • Cannot determine MIC
  • E-test = strip w/ antibiotic gradient
    • MIC = intersection of zone of inhibition and strip
76
Q

What is a toxoid?

A

A chemically treated toxin that is no longer toxic but retains immunogenicity

Example: Diphtheria toxoid = vaccine that protects against diphtheria

77
Q

Give some examples of macrolide antibiotics

A
  • Azithromycin
  • Clarithromycin
  • Erythromycin
78
Q

Which antibiotic is generally used to treat Streptococus pyogenes?

A

Penicillin;

Most strains are susceptible; Streptococcus spp. do not make beta-lactamase

79
Q

How can gut flora be maintained or re-populated during and after the course of an antibiotic prescription?

A
  • Probiotic
    • Give good bacteria
  • Prebiotic
    • Give nutrients to promote the growth of good bacteria
  • Bacteriotherapy
    • Stool transplant
    • Used in very serious C. diff infections
80
Q

How can you determine MIC breakpoint from a Kirby-Bauer test?

A

You can’t

However, you can compare the diameter of the zone of inhibition to standard values for that antibiotic to determine susceptibility

81
Q

Which cephalosporins are active against pseudomonas?

A

Ceftazidime (3rd)

Cefepime (4th)

82
Q

What is the MIC breakpoint?

A

The concentration (mg/L) fo an antibiotic that defines whether a species of bacteria is susceptible or resistant to the antibiotic

If MIC < MIC breakpoint, the bacteria is susceptible

(Basically, the antibiotic has to work against the bacteria at a concentration that you would actually want to give to a patient)

83
Q

Which antibiotics are most closely associated with C. diff infection?

A

Bacterial Vacation Finds C.diff Spores

  • Beta-lactamase inhibitor combinations
  • Vancomycin
  • Fluoroquinolones
  • Cephalosporins
  • Sulfa-drugs

Note: all antibiotics except Metronidazole has the potential to cause a C. diff infection

84
Q

What kind of vaccine is the HPV vaccine?

Who is it recommended for?

A

Fractional virus

Nonavalent virus-like particle that self-assembles
(with no viral DNA inside)

Recommended for everyone; prevents cancer

85
Q

In general, which antibiotics are bactericidal?

Are there exceptions?

A

In general, cell wall agents are bactericidal

Exception: Aminoglycosides inhibit protein synthesis, but are also bactericidal

86
Q

Describe a scenario in which therapeutic drug monitoring would be useful

A
  • There is a direct relationship between drug concentraion and efficacy or toxicity
  • Inter-patient variability in serum concentration if the standard dose is given
  • Narrow therapeutic window
  • Clinical efficacy or toxicity is delayed/difficult to measure
  • There is a reliable assay to use to monitor the drug
87
Q

What does it mean for an antibiotic to be bacteriostatic?

A

The antibiotic inhibits the growth of bacteria

Killing of the bacteria is dependent on the host immune system

88
Q

Which toxicity is most commonly associated with Daptomycin?

89
Q

What kind of vaccine is the varicella vaccine?

A

Live attenuated VZV

90
Q

Which vaccine is recommended to prevent Herpes Zoster Virus?

Who is it recommended for?

A

Shigrix: VZV glycoprotein E antigen with ASO1B adjuvant

(A fractional vaccine)

Recommended for all adults (even those who have not had chickenpox; may be infected with VZV without classic primary presentation)

91
Q

Which infections can be treated by aminopenicillins like ampicillin or amoxycillin?

A

Streptococci

(Vulnerable to beta-lactamase)

92
Q

Which generation of cephalosporin is cefepime?

What is it active against?

A

4th generation

  • Good gram positive coverage
    • Strep and MSSA
  • Good gram negative coverage
    • Enerobacteriacea
    • Pseudomonas
93
Q

What are the toxicities associated with metronidazole?

A
  • Disulfram-like effect (makes people very sick if they drink alcohol)
  • Metallic taste in mouth
  • No detectable levels in the serum unless intestinal inflammation or renal impairment
94
Q

What does an inactivated virus contain?

What is the effect on the host?

A
  • A whole killed bacterial cell OR fractional/subunit components
  • Cannot cause disease or replicate in the host
  • Causes a mostly humoral immune response that may diminish over time
95
Q

What does it mean for an antibiotic to be bactericidal?

A

The antibiotic causes the death of the bacteria

(Killing does not depend on host factors)

96
Q

Which infections can be treated by a glycopeptide (vancomycin)?

A

Gram (+) species only

  • MSSA
  • MRSA
  • Streptococcus epidermidis
  • Most enterococci (except those encoding VanA, which would make them resistant)
97
Q

Which agents have activity against gram-positive bacteria?

A
  • Beta-lactams
    • Penicillins
    • Cephalosporins
    • Carbapenems
    • Not monobactams
  • Glycopeptides (Vancomycin)
  • Trimethoprim-sulfamethoxazole
  • Oxazolidinones (Linezolid)
  • Lipopeptides (Daptomycin)
98
Q

List the arguments in favor of “double coverage” antibiotic prescription

A
  • Synergy = more effective bacterial killing
  • Cover the odds in empiric treatment
    • You’re more likely to cover the pathogen
  • Prevent the emergence of resistance
99
Q

Which beta-lactam antibiotic is active against most gram negative bacteria?

A

Carbapenems

We want to “save” these; if a bacteria is resistant to carbapenem, we’re kind of screwed

100
Q

Which infections can be treated by natural penicillins?

A
  • Streptococci
  • Meningococci
  • Some enterococci
  • Penicillin-susceptible pneumococci

(Vulnerable to beta-lactamase)

101
Q

What is the mechanism of action of macrolide antibiotics?

A

Inhibit protein synthesis by inhibiting the bacterial ribosome (50S subunit)

This prevents peptidyl transferase from adding the growing peptide chain to the next amino acid

102
Q

What is the difference between Dtap and Tdap?

A
  • Both
    • Protect against dipheria, tetanus, and pertussis
    • The diphtheria and tetanus components in both vaccine are toxoids
  • Dtap
    • Pertussis component is killed whole cell
    • Greater efficacy, but more adverse effects
  • Tdap
    • ​Pertussis component is an acellular subunit
    • Less effective, wears off over time
    • Fewer adverse effects
103
Q

What drives allergic reactions to beta-lactam antibiotics?

What does this mean for cross-reactivity?

A

Allergic reaction to beta-lactams is driven by their side chains

  • Cross-reactivity is most likely to occur between agents with similar side chains
  • Distantly-related side chains are less likely to cross react
  • Aztreonam is structurally different from other beta lactams => typically safe to give to people with allergies to other beta-lactams
104
Q

In which clinical situations would you use daptomycin?

Why?

A

Daptomycin provides excellent gram (+) coverage, but it would not be prescribed in most clinical situations

  • Use as a “last resort” antibiotic when all else has failed
    • Prevent muscle toxicity
    • Good antibiotic stewardship (save the big guns only for when they’re needed)
    • These drugs are expensive
105
Q

What kind of antibiotics are -mycins or -micins?

A

Aminoglycosides; inhibit the 30s subunit of the bacterial ribosome to inhibit protein synthesis

106
Q

In which clinical situations would vancomycin be the best choice of antibiotic?

Why?

A

An inpatient who has a serious infection caused by a gram (+) bacteria, especially if penicillin has not been active against the infection

  • Vancomycin is active against a broad spectrum of gram (+) bacteria
  • Lack of susceptibility to penicillin indicates that the bacteria either
    • a) synthesizes beta-lactamase or
    • b) has alternative penicillin binding proteins
  • Vancomycin works against either of these bacteria becase it binds to D-alanyl-D-alanine, instead of PBP
  • Vancomycin to treat this kind of infection must be given via IV; oral vancomycin is not absorbed into the systemic system
107
Q

What is Steven-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)

Which antibiotic is it associated with?

A

Severe adverse reaction characterized by…

  • Fever
  • Mucocutaneous lesions
  • Sloughing of the epidermis

Most commonly associated with trimethoprim-sulfamethoxazole

108
Q

Which infections can be treated with anti-staphylococcal penicillins like oxacillin?

A
  • MSSA
  • Some streptococci
109
Q

Which feature of the pathogenesis of bacterial meningitis makes the infection easier to treat?

A

Inflammation due to bacterial infection makes the blood-brain barrier more permeable

  • Tight junctions open
  • Bacteria can permeate the CSF, but antibiotics can too!
110
Q

Which organisms are later-generation cephalosporins most effective against?

A

Later generation cephalosporins provide broader coverage, especially for gram (-) organisms. Most maintain their coverage against gram (+) organisms

111
Q

What are the major mechanisms that confer antibiotic resistance?

A
  • Reduced entry (alteration of porins)
  • Increased efflux (overexpression of pumps)
  • Enzymes that destroy the antibiotic (ex: beta-lactamase)
  • Alteration of the target molecule
  • Increased binding sites for the antibiotic (thick cell wall)
  • Alteration of microbial proteins that activate pro-drugs
  • Alterantive pathways to those inhibitied by the antimicrobial

(Last 3 apply more to antivirals)

112
Q

Which vaccines can initiate a cell-mediated immune response?

A. Live, attenuated vaccine

B. Inactivated vaccine

A

Both can initiate a cell-mediated immune response

All live attenuated vaccines will initiate a cell-mediated response

All whole cell vaccines will initate a cell-mediated response

Fractional vaccines that contain peptides (ex: toxoid, polysaccharide conjugated to a protein) will initiate a cell-mediated response

(Fractional vaccines that contain only polysaccharides will not initiate a cell-mediated response)

113
Q

Give some examples of tetracycline antibiotics

A
  • Doxycycline
  • Minocycline
  • (anything ending with -cycline)
114
Q

What is the mechanism of action of metronidazole?

A

Metabolites of the antibiotic damage the DNA of bacteria

115
Q

A patient is scheduled for throacic surgery. To prevent an incision site infection, the surgeon orders prophylactic antibiotics.

  1. What microbes are you worried about?
  2. What antibiotics would be appropriate?
A
  1. Gram (+) microbes
  2. Cephazolin (IV) or cephalexin (oral)
116
Q

Which infections can be treated with lipopeptides (ex: daptomycin)

A

Gram (+) only, but wide range

  • MSSA
  • MRSA
  • Strep, epidermidis (but not the causative agent of cellulitis)
  • Most enterococci
117
Q

What is a “post-antibiotic effect?”

A

The antibiotic keeps killing microbes even after the serum concentration has fallen below MIC

Exhibited by concentration-dependent antibiotics

118
Q

What are the 4 methods by which bacteria gain antibiotic resistance?

A
  • Horizontal
    1. Transduction
    2. Transformation
    3. Conjugation
  • Vertical
    1. Spontaneous mutation
119
Q

What does the pneumococcal vaccine contain?

Who is it recommended for?

A

Subunit conjugate; 13-valent

Recommended for anyone with increased risk of bacterial pneumococcal disease

  • Immunocompromised
  • No functional spleen
  • CSF leak
  • Cochlear implants
  • Adults >60 yo
    • Note: immunizing children provides herd immunity for aging adults
120
Q

How can C. diff infection be prevented?

List 2 ways

A
  • Healthcare workers should clean their hands to prevent the spread of spores
  • Don’t prescribe antibiotics unless absolutely necessary
121
Q

Which beta-lactam antibiotic has activity against MRSA?

A

Ceftaroline (4th generation cephalosporin)

122
Q

Which bacteria should be covered by empiric antibiotic treatment of community-acquired pneumonia?

Which agent shoud you use?

A

Bacteria

  • Staphylococcus peumoniae (Gram +)
  • Legionella pneumophila (Atypical)
  • Chlamydophila pneumonia (Gram -)

Treatmetn = one of the following

  • Fluoroquinolone w/ Gram negative coverage
    • Ceftriaxone, ceftazidime, cefipime
  • Doxycycline (a tetracycline)
  • Azithromycin (a macrolide)
123
Q

Describe the general spectrum of fluoroquinolone antibiotics

A

Broad spectrum against gram-negative, gram-positive, and atypical organisms

124
Q

What do you need to consider when choosing an antibiotic for empiric treatment of bacterial meningitis?

Which agents do you choose?

A

The agent must…

  • Cover streptococcus pneumoniae and neisseria meningitidis
  • Be able to reach the CSF

You should choose both…

  • Ceftriaxone
    • Can penetrate the CSF at high doses without toxicity
    • Low affinity for the membrane transporter that would promote efflux
    • Active against both bacteria
  • Vancomycin
    • Active against penicillin-resistant staphylococcus pneumoniae
    • Usually cannot penetrate CSF, but may be able to due to meningitis-related inflammation
125
Q

Describe the spectrum and clinical use of macrolide antibiotics

A
  • Spectrum
    • Gram positive
      • S. pneumoniae
    • Gram negative
      • Agents that cause respiratory infection
        • H. influenzae
        • Neisseria spp.
        • B. pertussis
        • Campylobacter
    • Atypical
      • Mycoplasma
      • Legionella
      • Chlamydia
  • Clinical use
    • Best thing to use for community-acquired pneumonia
126
Q

Describe the spectrum and clinical use of moxifloxacin

A

Moxifloxacin = respiratory fluoroquinolone

  • Spectrum
    • Gram positive
    • Gram negative
    • Atypical
  • Clinical use
    • Community-acquired pneumonia when coverage for streptococcus pneumoniae is needed
    • Note: no urinary concentration = not effective against UTI
127
Q

Which antibiotics inhibit bacterial Coenzyme-A?

A

Nitrofurantoin

128
Q

Which generation of cephalosporin is ceftriaxone?

What is it active against?

A

3rd generation

  • Reduced gram (+) coverage
    • Still active against pneumococci, staphylococci
  • Improved gram (-) coverage
    • Citrobacter
    • S. marscens
    • Providencia
129
Q

Which types vaccines are more likely to lose efficacy over time?

A. Live, attenuated vaccine

B. Inactivated vaccine

A

B. Inactivated vaccine

130
Q

Which beta-lactamase is not active against gram positive bacteria?

A

Monobactams

131
Q

What is the general mechanism of oxazolidinone antibiotics?

A

Inhibit bacterial protein synthesis

Bind the 23S ribosomal RNA in the 50S subunit

(unique binding site = no cross-resistance)

132
Q

Describe the spectrum and clinical use of ciprofloxacin

A

Ciprofloxacin is a fluoroquinolone

  • Spectrum
    • Gram negative
    • Pseudomonas
    • Atypical
  • Clinical uses
    • Treat UTI (simple cystitis)
      • Active against enterobacteriaceae
133
Q

What is the mechanism of action of nitrofurantoin?

A

Inhibits bacterial coenzyme-A

  • Interferes with carbohydrate metabolism and cell wall formation
134
Q

Which antibiotics act by inhibiting the bacterial ribosome?

A

30S

  • Tetracycline
  • Aminoglycoside

50S

  • Macrolide
  • Clindamycin
  • Erythromycin
  • Linezolid (Binds 23S RNA)
  • Chloramphenicol
135
Q

Which antibiotics are concentration-dependent?

A

All beta-lactams

Linezolid

136
Q

Which infections can be treated with trimethoprim-sulfamethoxazole?

A
  • MSSA
  • MRSA (most)
  • Some Streptococcus spp.
    • But NOT the causative agent of cellulitis
  • Enterobacteriaceae
137
Q

Which drugs are concentration and time-dependent?

A

Vancomycin

Daptomycin

Tetracycline

Macrolides

138
Q

Which toxicity is most commonly associated with Linezolid?

A

Bone marrow suppression

139
Q

What is the mechanism of aminoglycoside antibiotics?

A

Inhibit protein synthesis

  • Bind to the 30s ribosomal subunit
    • Block initiation complex
    • Cause misreading of mRNA -> errors in peptide chain
    • Block movement of the ribosome; mRNA forms a complex with a single, nonfunctional monosome (rather than a polysome)
140
Q

Which organisms are first-generation cephalosporins most effective against?

A

Gram (+) bacteria

141
Q

List 4 potential negative consequences of antibiotic use

A
  • Toxicity
    • Including allergic reactions
  • C. diff infection
  • Development of antibiotic resistance
  • Disruption of the normal flora
    • Can lead to vomiting, diarrhea, etc.
142
Q

In a time-concentration curve, which measurement represents the total concentration of the drug?

A

Area under the curve (AUC)

143
Q

Which agents are active against MRSA?

A

Lineman TouchDown, Very Cool

  • Linezolid
  • Trimethoprim-sulfamethoxazole
  • Daptomycin
  • Vancomycin
  • Clindamycin (but confirm susceptibility with D-test)

(Football players get MRSA because contact sports; it’s very cool if a lineman scores a touchdown because it doesn’t happen often)

144
Q

Describe the spectrum and clinical uses of tetracycline antibiotics

A
  • Spectrum = broad (one of the broadest)
    • Gram positive
    • Gram negative
    • Anaerobes
    • Atypicals
      • Chlamydiae, mycoplasma, legiionella
  • Clinical uses
    • Treat Rickettsiae and Borreliae infections
      • Rocky mountain spotted fever
      • Lyme disease
    • Efficacy against intracellular pathogens (like rickettsiae)
145
Q

Describe the spectrum and clinical use of nitrofurantoin

A
  • Spectrum
    • Gram negative
      • Enterobacteraciae
      • E. coli
    • Gram positive
      • Staphylococcus saprophyticus
  • Clinical use
    • Only used to treat UTI
146
Q

What vaccines are recommended for pregnant women?

A
  • Tdap with every pregnancy
  • Flu vaccine (Inactivated TIV, not LAIV)
  • If necessary (not previously administered)
    • Hep A vaccine
    • Hep B vaccine
    • Meningococcal vaccine (protects against Nesseria meningitidis)

Do not give live, attenuated vaccines

147
Q

Describe the spectrum and clinical use of aminoglycoside antibiotics

A
  • Spectrum
    • Aerobic, gram-negative rods
    • Includes multi-drug resistant enterobacteriaceae
    • Pseudomonas
  • Clinical use
    • Treatment for the above gram-negative organisms
    • Synergy with another antibiotic class to treat serious staphylococcal or enterococcal infections
      • Not effective alone against gram-positive organisms
148
Q

Which vaccines are NOT recommended for pregnant and immunocompromised patients?

A. Live, attenuated vaccine

B. Inactivated vaccine

A

A. Live, attenuated vaccine

149
Q

What are the 3 key parameters that determine the effect of an antibiotic on the bacterial population?

A
  • EC50
  • EMax
  • H: The slope of the curve (aka Hill factor)
150
Q

Which infections can be treated by beta-lactam/beta-lactamase inhibitor combos such as ampicillin/sulbactam or piperacillin/tazobactam?

A
  • MSSA
  • Streptococcus
  • Anaerobic bacteria
  • E. coli

Beta-lactamase inhibitor = can kill bacteria that make beta-lactamase!

151
Q

What are the 4 major beta-lactam antibiotics?

A

Penicillins, Cephalosporins, Monobactams, Carbapenems

152
Q

List 3 macrolide antibiotics

A

Azithromycin

Erythromycin

Clarithromycin

153
Q

What are some features of tetracycline that make it an effective antibiotic?

A
  • It is distributed widely to tissues
  • Effective against intracellular bacteria
  • Broad spectrum
154
Q

Which generation of cephalosporin is ceftazidime?

What is it active against?

A

3rd generation

  • No gram (+) coverage
  • Improved gram (-) coverage
    • Citrobacter
    • S. marscens
    • Providencia
155
Q

Which class of antibiotics is associated with achilles tendon rupture?

A

Fluoroquinolones

156
Q

What is the most worrisome toxicity related to macrolide antibiotics?

A

Cardiac

  • Macrolides may prolong the QT interval and cause arrhythmia
  • Toxicity is more likely in patients with coronary artery disease
157
Q

Which toxicity is most commonly associated with Trimethoprim-sulfamethoxazole?

A

Stevens-Johnson syndrome

(Severe reaction characterized by fever, mucocutaneous lesions, sloughing of the epidermis)

158
Q

Which toxicity is most commonly associated with Beta-lactams?

A

Allergic reactions/anaphylaxis

FDN3 Minnie (14 decks)

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