Antibiotics/Vaccines Flashcards Preview

FDN3 By Nathan and Minnie > Antibiotics/Vaccines > Flashcards

Flashcards in Antibiotics/Vaccines Deck (191)
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1
Q

What is the general mechanism of fluroquinolone antibiotics?

A

Quinolones inhibit DNA gyrase; they prevent the separation of sister chromatids after DNA replication

2
Q

What is the general mechanism of beta lactam antibiotics?

A

Beta lactam antibiotics inhibit bacterial wall synthesis by interfereing with peptidoglycan formation

3
Q

What is the general mechanism of tetracycline antibiotics?

A

Inhibit the bacterial ribosome

4
Q

What is the general mechanism of aminoglycoside antibiotics?

A

Inhibit protein synthesis by inhibiting the 30s ribosomal subunit

5
Q

What is the general mechanism of macrolide antibiotics?

A

Inhibit the bacterial ribosome

6
Q

What is the general mechanism of oxazolidinone antibiotics?

A

Inhibit the bacterial ribosome

7
Q

What is the general mechanism of lincosamide antibiotics?

A

Inhibit the bacterial ribosome

8
Q

What is the general mechanism of rifampin antibiotics?

A

Rifampin antibiotics inhibit RNA polymerase

9
Q

What is the general mechanism of sulfonamide antibiotics?

A

Inhibit the folic acid pathway

10
Q

Which antibiotic is generally used to treat Streptococus pyogenes?

A

Penicillin;

Most strains are susceptible

11
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)
12
Q

Which organisms are first-generation cephalosporins most effective against?

A

Gram (+) bacteria

13
Q

Which organisms are later-generation cephalosporins most effective against?

A

Later generation cephalosporins provide broader coverage, especially for gram (-) organisms

14
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)

15
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

16
Q

What kind of antibiotic is trimethoprim/sulfamethoxazole?

A

A sulfonamide

Sulfonamides inhibit the folate synthesis pathway

17
Q

What kind of antibiotics are -floxacins?

A

Fluoroquinolones;

They directly inhibit bacterial DNA synthesis

18
Q

What kind of antibiotics are -mycins or -micins?

A

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

19
Q

What kind of antibiotic is carbapenem?

A

A beta-lactam; interferes with peptidoglycan synthesis

20
Q

What are the 4 major beta-lactam antibiotics?

A

Penicillins, Cephalosporins, Monobactams, Carbapenems

21
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

22
Q

What is empiric antibiotic therapy?

A

Choosing an antibiotic based on

  • Guidelines for recommendations
  • Knowledge of the organism that typically causes a certain infection
  • Knowledge of the susceptibilities of organisms present in a certain setting
23
Q

What is directed therapy?

A

Choosing an antibiotic based on knowledge of what organism is causing an infection and what antibiotics it is susceptible

(such as results from a wound culture)

24
Q

What is an example of a broad spectrum beta-lactam with both gram-positive and gram-negative coverage?

A

Piperacillin-tazobactam

25
Q

What is the mechanism of action of beta-lactams?

A

Binding and inhibiting PBPs, causing termination of peptidoglycan structure, interfering with synthesis of the cell wall and leading to cell death

26
Q

What are the mechanisms of bacterial resistance to beta-lactams?

A
  • Beta-lactamases: enzymes that destroy beta-lactam antibiotics (penicillinases: penicillin resistance in Staph aureus)
  • Alteration of pencillin binding proteins (PBP2a of MRSA has low affinity for beta-lactams and renders MRSA resistant)
27
Q

What groups of antibiotics are in the beta-lactam class?

A
  • Penicillins
  • Cephalosporins
  • Monobactams
  • Carbapenems
28
Q

What is an example of a glycopeptide antibiotic?

A

Vancomycin

29
Q

What is the mechanism of action of glycopeptides (vancomycin)?

A

Inhibiting bacteria cell wall synthesis by binding to D-alanyl-D-alanine terminus and blocking linkage to glycopeptide polymer

30
Q

What are the mechanisms of bacterial resistance to glycopeptides (vancomycin)?

A
  • Change in peptidoglycan with reduced binding to vancomycin (terminus altered to D-ala-D-lactate or D-ala-D-serine)
  • Production of thick cell wall with increased or false targets for vancomycin
31
Q

What is an example of a lincosamide antibiotic?

A

Clindamycin

32
Q

What is the mechanism action of action of lincosamides (clindamycin)?

A

Inhibits protein synthesis by binding to the 50s subunit of the ribosome and blocking peptide bond formation

33
Q

What are the mechanisms of bacterial resistance to lincosamides (clindamycin)?

A
  • Methylation of the 50s subunit prevents clindamycin attachment
  • Cross resistance with macrolides
34
Q

What is an example of a folate antagonist antibiotic?

A

Trimethoprim-sulfamethoxazole

35
Q

What is the mechanism of action of folate antagonist antibiotics (trimethoprim-sulfamethoxazole)?

A

Blocks sequential steps in folate metabolism (synergistic combo)

36
Q

What are the mechanisms of bacterial resistance to folate antagonist antibiotics (trimethoprim-sulfamethoxazole)?

A
  • Increased PABA concentration
  • Enzymes with reduced affinity
  • Loss of permeability
37
Q

What is an example of an oxazolidinone?

A

Linezolid

38
Q

What is the mechanism of action of oxazolidinones (linezolid)?

A

Inhibit protein synthesis by binding to the 23S portion of the 50S subunit and preventing formation of ribosomal complex

39
Q

What is the mechanism of bacterial resistance to oxazolidinones (linezolid)?

A

Point mutation in 23S rRNA

40
Q

What is an example of a lipopeptide antibiotic?

A

Daptomycin

41
Q

What is the mechanism of action of lipopeptides (daptomycin)?

A
  1. Bind to cell membran
  2. Cause depolarization due to K+ efflux
  3. Depolarization disrupts cellular processes and leads to cell death
42
Q

What is the mechanism of bacterial resistance to lipopeptides (daptomycin)?

A

Not characterized yet

43
Q

Describe the differences among the generations of the cephalosporin classes

A
  • There is increasing gram-negative coverage as you progress from the 1st through the 4th generations of cephalosporins
  • Gram-positive coverage
    • 1st and 4th generations have good streptococcal and staphylococcal coverage
    • 2nd generation has poor coverage
    • 3rd generation: ceftriaxone has good coverage but ceftazidime has no coverage
44
Q

Name two agents from the beta-lactam class that have activity against both Gram-positive and Gram-negative organisms

A

Cefazolin

Imipenem

Others

45
Q

Why would a clinician not want to use the broadest, most potent antibiotic in all circumstances?

A

Using unnecessarily broad antibiotics will

  • Kill more of the normal flora
  • Be more likely to select for future resistance
46
Q

What are examples of fluoroquinolones?

A
  • Ciprofloxacin
  • Moxifloxacin
  • Levofloxacin
47
Q

What is the mechanism of action of fluoroquinolones (ciprofloxacin, moxifloxacin, levofloxacin)?

A

Disrupting DNA synthesis by interacting with DNA gyrase (topoisomerase II) and DNA topoisomeraise IV

Bacterial cell growth inhibiting by trapping the enzymes in a complex

Bacterial cell death due to DNA cleavage and inability to repair DNA

48
Q

What is the function of DNA gyrase (DNA topoisomerase II) in bacteria?

A

Relaxes DNA supercoiling during transcription and replication

49
Q

What is the function of DNA topoisomerase IV in bacteria?

A

Separates replicated DNA into daughter cells

50
Q

What are the mechanisms of bacterial resistance to fluoroquinolones (ciprofloxacin, moxifloxacin, levofloxacin)?

A
  • Point mutation in DNA gyrase or topoisomerase results in conformational change and inability of fluoroquinolones to bind
  • Efflux pumps pump out fluoroquinolones
  • Reduction in porin channels prevents fluoroquinolones from entering bacterial cell
51
Q

What is an example of a nitrofuran antibiotic?

A

Nitrofurantoin

52
Q

What is the mechanism of action of nitrofurantoin?

A
  • Inhibits bacterial Acetyl-CoA, interfering with carbohydrate metabolism
  • Disrupts bacterial cell wall formation
53
Q

What are examples of aminoglycosides?

A
  • Gentamicin
  • Amikacin
  • Tobramycin
  • Streptomycin
  • Neomycin
54
Q

What is the mechanism of action of aminoglycosides?

A

Interfering with protein synthesis by binding to 30s ribosomal subunit

  • Blocks formation of initiation complex between 50S and 30S subunits
  • Misread mRNA leading to miscoded peptide chain
  • Block translocation on mRNA
55
Q

What are the mechanisms of bacterial resistance to aminoglycosides?

A
  • Bacterial transferase enzyme inactivates aminoglycoside
  • Fewer porin channels decrease drug entry into bacterial cells
  • Conformational change in 30S subunit prevents binding
56
Q

What is the minimum inhibitory concentration (MIC)?

A

Lowest concentration of an antibiotic that prevents visible growth of bacteria after 18-24 hours of incubation

57
Q

What is the minimum bactericidal concentration (MBC)?

A

Lowest concentration of an antibiotic that results in complete killing of bacteria

58
Q

What is the MIC breakpoint?

A

Antibiotic concentration that separates strains where there is a high likelihood of treatment success from those bacteria where treatment is more likely to fail

“clinical cut-off”

59
Q

When can a drug be used while considering MIC and breakpoint?

A

When MIC is under the breakpoint

(ideally want MIC as far from breakpoint as possible)

60
Q

When is a bacteria sensitive to an antibiotic?

A

When growth of the organism is inhibited by the antibiotic concentration lower than the breakpoint

61
Q

Which is the best aminoglycoside to use?

A

Trick question! You need to have the MIC breakpoint to answer the question

62
Q

What is the best aminoglycoside to use?

Why?

A

Amikacin

Amikacin MIC is two dilutions away from the breakpoint, which is a larger difference than tobramycin (MIC is one dilution away from the breakpoint) or gentamicin (MIC is at the breakpoint)

63
Q

When is interpreting MICs most critical?

A
  • For the sickest patients
  • For multi-drug resistant organisms
64
Q

Can you compare the absolute number of MICs between antibiotic classes or between antibiotics in the same class?

A

No. Cannot compare absolute number of MICs between antibiotic classes or between antibiotics within same class

65
Q

Describe the difference between microbroth dilution, Kirby-Bauer test, and E-test

A
  • All these methods determine MIC by evaluating what concentration of antibiotic effectively kills the bacteria being tested
  • Microbroth dilution utilizes tubes or wells of antibiotics into which the bacteria are inoculated
  • Kirby-Bauer test uses discs impregnated with antibiotic placed on an agar plate inoculated with bacteria
  • E-test is a strip that has a gradient of antibiotic concentrations that is placed on an agar plate inoculated with bacteria
66
Q

You are seeing a patient with community-acquired pneumonia. You remember you need to cover Streptococcus pneumoniae as well as atypical organisms such as Legionella pneumophila and Chlamydophila pneumoniae. Which agents would achieve intracellular penetration and be active against atypicals?

A
  • Fluoroquinolones
  • Tetracyclines (doxycycline)
  • Macrolides (azithromycin)
67
Q

What is the mechanism of action of tetracyclines?

A

Inhibiting protein synthesis by binding reversibly to the 30S ribosome

68
Q

What are the mechanisms of bacterial resistance to tetracyclines?

A
  • Impaired influx or increased efflux by an active transport protein pump
  • Ribosome protection due to production of proteins that interfere with tetracycline binding to the ribosome
  • Enzymatic inactivation
69
Q

What are the uses/spectrum of tetracyclines?

A
  • Gram-positive
  • Gram-negative
  • Anaerobic
  • Atypical organisms (Chlamydiae, Mycoplasma, Legionella)
  • Ricketssiae and Borreliae spp. (Rocky Mountain spotted fever, Lyme disease)

(distributed widely to tissues and fluids, good intracellular activity)

70
Q

What is does it mean if an antibiotic acts by concentration-dependent killing?

A

The rate of bactericidal killing is mazimized at the peak concentration (Cmax) in the serum

71
Q

For an antibiotic that acts by concentration-dependent killing, what occurs after drug concentrations decrease to levels below the MIC?

A

Persistent suppression of growth

due to post-antibiotic effect (PAE)

72
Q

For an antibiotic that acts by concentration-dependent killing, why is there persistent suppression of growth after drug concentrations decrease to levels below the MIC?

A

Post-antibiotic effect

73
Q

What is the relationship between drug concentration and the duration of post-antibiotic effect and residual bacterial population for an antibiotic that acts by concentration-dependent killing?

A

The higher the drug concentration, the longer the duration of the PAE and the smaller the residual bacterial population when the next dose is given

74
Q

Which classes of antibiotics act by concentration-dependent killing?

A
  • Aminoglycosides
  • Fluoroquinolones
75
Q

What does it mean if an antibiotic acts by time-dependent killing?

A

Bacterial killing occurs while serum concentrations remain above the MIC

Goal is to keep antibiotic concentrations higher than the MIC for as much of the dosing interval as possible (at least 40-50%)

76
Q

For an antibiotic that acts by time-dependent killing, what do you want the antibiotic concentrations to be?

A

Goal is to keep antibiotic concentrations higher than the MIC for as much of the dosing interval as possible (at least 40-50%)

77
Q

For an antibiotic that acts by time-dependent killing, what is the effect of achieving high peak serum concentrations?

A

For an antibiotic that acts by time-dependent killing, achieving high peak serum concentrations has no effect upon bacterial killing

78
Q

For an antibiotic that acts by time-dependent killing, is there a post-antibiotic effect?

A

Minimal to no PAE for an antibiotic that acts by time-dependent killing

79
Q

What class of antibiotics acts by time-dependent killing?

A

Beta-lactams

(also Linezolid)

80
Q

What two drugs is therapeutic drug monitoring usually used for?

A
  • Vancomycin
  • Gentamicin
81
Q

Why would a clinician employ therapeutic drug monitoring?

A
  • Assure therapeutic dosing is achieved
  • Avoid toxicity
  • When there are conditions which will alter standard distribution or clearance (obesity, renal impairment)
82
Q

What are the goal troughs for vancomycin used to treat a non-severe infection?

A

10-15 ug/mL

83
Q

What are the goal troughs for vancomycin used to treat a deep-seated infection?

A

15-20 ug/mL

(bacteremia, endocarditis, osteomyelitis, prosthetic joint infection, pneumonia warranting hospitalization, infections of the CNS)

84
Q

What is the rationale for using therapeutic drug monitoring? (5)

A
  • A direct relationship exists between drug concentration and efficacy or toxicity
  • Substantial interpatient variability exists in serum concentrations on standard doses
  • There is a small difference between therapeutic and toxic serum concentrations (small therapeutic window)
  • Clinical efficacy or toxicity of the drug is delayed or difficult to measure
  • An accurate assay is available
85
Q

What are bacteriocidal agents (antibiotics)?

A

Cause death of bacteria

Killing of organism depends less on host factors

86
Q

What are bacteriostatic agents (antibiotics)?

A

Inhibit the growth of bacteria

Killing of the organism depends on host defense mechanisms

87
Q

In general, which antibiotics are bactericidal?

A

Cell-wall active agents

88
Q

In general, which antibiotics are bacteriostatic?

A

Antibiotics that inhibit protein synthesis (except aminoglycosides)

89
Q

What conditions is it optimal to use bactericidal antibiotics for?

A
  • Septic shock
  • Meningitis
  • Endocarditis
  • Impaired immune system
  • Chemotherapy-induced neutropenia with infection
90
Q

For which populations/syndromes is it optimal to use a bactericidal agent for?

A. Adult with meningitis

B. Leukemic patient with fever and neutropenia

C. Child with pneumonia

D. All of the above

A

All the above!

91
Q

Which PK/PD parameters are unique to antibiotics?

A

Time-dependent killing and concentration-dependent killing

92
Q

What is the best choice for an antibiotic to treat C. difficile infection?

A

Oral vancomycin

93
Q

What is the only indication for oral vancomycin?

A

Treatment of C. difficile collitis

(drug is not systematically absorbed, no significant toxicity, not useful for treating infection outside of the intestines)

94
Q

What is the toxicity of metranidazole?

A
  • Headache
  • Nausea
  • Decreased appetite
  • Metallic taste
  • Disulfiram-like effect
  • Neuropathy
95
Q

Which type of bacteria/pathogens does metronidazole target?

A

Anaerobes: all anaerobic cocci and both gram-negative bacilli, including Bacteroides spp., and anaerobic spore-forming Gram-positive bacilli

Protozoa: trichomonas, giardiasis, and amebiasis

96
Q

How is metranidazole administered to treat C. difficile infection?

A

Orally

97
Q

What is the mechanism of action of metronidazole?

A

Metabolites damage DNA

98
Q

Which class of antibiotics is metranidazole included in?

A

Nitroimidazole

99
Q

What is the preferred treatment strategy for C. difficile infection?

A

Oral vancomycin is best choice

Metranidazole is second choice

100
Q

What is the relationship between antibiotic exposure and risk of C. difficile infection?

A

Dose-response effect

Longer the treatment with antibiotic, the greater the risk of C. diff infection

Greater the number of antibiotics used, the greater the risk of C. diff infection

101
Q

What are three examples of macrolide antibiotics?

A
  • Erythromycin
  • Clarithromycin
  • Azithromycin
102
Q

What is the mechanism of action of macrolides (erythromycin, clarithromycin, azithromycin)?

A

Inhibiting protein synthesis by binding to the 50S subunit of the ribosome and blocking peptide bond formation

103
Q

What is the spectrum of coverage of macrolides (erythromycin, clarithromycin, azithromycin)?

A
  • Gram-positive: S. pneumoniae
  • Gram-negative: H. influenzae, Neisseria spp., B. pertussis, Campylobacter
  • Atypical: Mycoplasma, Legionella, Chlamydia
104
Q
A
105
Q

What is the toxicity of macrolides (erythromycin, clarithromycin, azithromycin)?

A
  • GI, especially diarrhea
  • Cardiac toxicity: prolonged QT interval leading to torsades des pointes, ventricular tachycardia, and sudden death
106
Q

Which patients are the cardiac toxicities of macrolides (erythromycin, clarithromycin, azithromycin) more likely to occur in?

A

Patients:

  • With coronary artery disease
  • On other drugs that predispose to arrhythmia
  • With electrolyte disturbances
107
Q

What are the toxicites of beta-lactams?

A
  • Allergic reactions
  • Anaphylaxis
108
Q

What is the toxicity of aminoglycosides?

A

Nephrotoxicity

109
Q

What is the toxicity of vancomycin?

A

Red Man’s Syndrome

(histamine is released and skin becomes itchy upon vancomycin infusion)

110
Q

What is the toxicity of fluoroquinolones?

A

Achilles tendon rupture

111
Q

What is the toxicity of linezolid?

A

Bone marrow suppression

112
Q

What is the toxicity of daptomycin?

A

Myopathy

113
Q

What is the toxicity of trimethoprim-sulfamethoxazole?

A

Stevens-Johnson Syndrome

114
Q

What are two ways to prevent C. difficile infection?

A
  • Do not prescribe antibiotics if patient does not have bacterial infection
  • Always clean your hands to prevent transmission
115
Q

Whaat are three ways in which a prescriber may reduce antibiotic resistance?

A
  • Avoid prescribing antibiotics if patient does not have a bacterial infection
  • Use the narrowest antibiotic appropriate for the infection
  • Use the shortest duration of antibiotic treatment appropriate for the infection
116
Q

What is an example of a common antibiotic toxicity shared by several classes of antibiotics?

A

Diarrhea

(many other answers would work here)

117
Q

What is an example of a toxicity unique to a single class of antibiotics?

A

Fluoroquinolones are the only drugs associated with Achilles tendon rupture

(many other answers would work here)

118
Q

If a patient tells you she has an allergy to penicillin, what factors would you evaluate to determine whether another beta-lactam agent should be used?

A
  • What was the reaction? (anaphylaxis vs rash)
  • What agent caused the reaction? (if amoxicillin or ampicillin, there is a good chance other beta-lactams could be used safely)
  • How long ago did the reaction occur? (some allergies can resolve over time)
  • Has she taken other beta-lactams without a reaction? (if yes, it should be safe to use that agent again)
119
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

120
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)
121
Q

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

A

Monobactams

122
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.

123
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
124
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
125
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)

126
Q

Which infections can be treated by natural penicillins?

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

(Vulnerable to beta-lactamase)

127
Q

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

A
  • MSSA
  • Some streptococci
128
Q

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

A

Streptococci

(Vulnerable to beta-lactamase)

129
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!

130
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)
131
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
132
Q

Which infections can be treated with trimethoprim-sulfamethoxazole?

A
  • MSSA
  • MRSA (most)
  • Some Streptococcus spp.
    • But NOT the causative agent of cellulitis
  • Enterobacteriaceae
133
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
134
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
135
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
136
Q

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

A

Monobactam (Aztreonam)

137
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
138
Q

Which beta-lactam antibiotic has activity against MRSA?

A

Ceftaroline (4th generation cephalosporin)

139
Q

Describe the general spectrum of fluoroquinolone antibiotics

A

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

140
Q

List 3 commonly used fluoroquinolone antibiotics

A

Ciprofloxacin

Moxifloxacin (Respiratory)

Levofloxacin (Respiratory)

141
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
142
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
143
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
144
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

145
Q

Which fluoroquinolones are active against pseudomonas aeruginosa?

A

Ciprofloxacin and levofloxacin

146
Q

Which fluoroquinolone is not active against gram-positive bacteria?

A

Ciprofloxacin

147
Q

List 3 aminoglycoside antibiotics

A

Gentamicin

Tobramycin

Amikacin

148
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
149
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

150
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
151
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
152
Q

Which antibiotics act by inhibiting the bacterial ribosome?

A

30S

  • Tetracycline
  • Aminoglycoside

50S

  • Macrolide
  • Clindamycin
  • Erythromycin
  • Linezolid (Binds 23S RNA)
  • Chloramphenicol
153
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)

154
Q

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

A

Penicillin, oxacillin

(ampicillin only has minimal gram-negative activity)

155
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)
156
Q

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

A

Area under the curve (AUC)

157
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

158
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
159
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
160
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)
161
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.
162
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

163
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
164
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
165
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
166
Q

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

A
  • Diarrhea
  • Anaphylaxis
  • Hepatotoxicity
  • Dermatological toxicity
    • Rash
167
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
168
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)

169
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

170
Q

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

A

20%

171
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

172
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
173
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
174
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
175
Q

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

A. Live, attenuated vaccine

B. Inactivated vaccine

A

B. Inactivated vaccine

176
Q

Which vaccines are NOT recommended for pregnant and immunocompromised patients?

A. Live, attenuated vaccine

B. Inactivated vaccine

A

A. Live, attenuated vaccine

177
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)

178
Q

What kind of vaccine is the measles vaccine?

A

Live attenuated vaccine

179
Q

What kind of vaccine is the varicella vaccine?

A

Live attenuated VZV

180
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)

181
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)

182
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
183
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
184
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

185
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)

186
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
187
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

188
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

189
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

190
Q

Which vaccine prevents Ebolavirus?

A

A monoclonal antibody vaccine is in development

It protects against Ebola Zaire

191
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