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
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
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
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
5
Q
Which PK/PD parameters are unique to antibiotics (as opposed to other drugs)?
A
T>MIC
6
Q
What kind of vaccine is the measles vaccine?
A
Live attenuated vaccine
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)
8
Q
Which beta-lactam antibiotic is not active against gram-positive bacteria?
A
Monobactam (Aztreonam)
9
Q
What kind of antibiotic is trimethoprim/sulfamethoxazole?
A
A sulfonamide
Sulfonamides inhibit the folate synthesis pathway, this inhibiting bacterial DNA synthesis
10
Q
Which toxicity is most commonly associated with aminoglycosides?
A
Neprotoxicity
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
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
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
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
- Low troughs are okay
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
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
17
Q
Which antibiotic covers all of the most probable causes of community-acquired pneumonia?
A
Macrolides (azythromycin, erythromyin, clarithromycin)
18
Q
What is the general mechanism of rifampin antibiotics?
A
Rifampin antibiotics inhibit RNA polymerase
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
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
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
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
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
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
25
List 3 commonly used fluoroquinolone antibiotics
Ciprofloxacin
Moxifloxacin (Respiratory)
Levofloxacin (Respiratory)
26
How is a C. diff treated?
Oral vancomycin = first choice
Metronidazole = alternative
27
Which penicillins are active against Staphylococcus spp?
Which are not?
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.
28
What kind of antibiotic is amoxicillin-clavulanate?
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**
29
What kind of antibiotics are **-floxacin**s?
Fluoroquinolones;
They directly inhibit bacterial DNA synthesis
They are bactericidal
30
Give 1-2 examples of cephalosporins from each generation
* 1st generation
* Cefazolin
* 2nd generation
* Cefuroxime
* 3rd generation
* Ceftriaxone
* Ceftazidime
* 4th generation
* Cefepime
* Ceftaroline
31
What percentage of patients will have at least 1 adverse effect after taking antibiotics?
20%
32
What is the mechanism of resistance against vancomycin?
Which bacteria are likely to become resistant?
Vancomycin acts by binding to D-alanyl-D-alanine
Some **enterococci and S. aureus spp** possess the mobile genetic element **v****anA**that changes this target to D-alanyl-D-lactate or D-alanyl-D-serine basically**ruining the binding site for vancomycin**
* S. aureus may also be resistant due to an **abnormally thick cell wall**
33
Which antibiotics are time-dependent?
Aminoglycosides
Fluoroquinolones
34
Which beta-lactam antibiotic provides the most comprehensive gram-negative coverage?
Meropenem
(Cefepime, piperacillin/taxobactam, aztreonam, ceftazidime are also pretty good aginst most enterobacteriaceae and pseudomonas)
35
Which beta-lactams are most likley to cause a morbilliform rash?
Ampicillin and amoxicillin
Even more common if pt. also has EBV
Other beta-lactams are likely to be safe
36
Which toxicity is most commonly associated with Fluroquinolones?
Achilles tendon rupture
(Achilles tendon ruption is **only** associated with fluoroquinolones)
37
As a prescriber, what are 3 ways that you can prevent antibiotic resistance?
* 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
38
Which generation of cephalosporin is cefuroxime?
What is it active against?
2nd generation
* Good gram (+) coverage
* Strep and MSSA
* Improved gram (-) coverage
39
Which cephalosporins have good gram positive coverage and the most limited gram negative coverage?
1st generation
Cefazolin
40
Compare the efficacy of conjugate vaccines with polysaccharide vaccines
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
41
Which fluoroquinolone is **not** active against gram-positive bacteria?
Ciprofloxacin
42
Which fluoroquinolones are active against pseudomonas aeruginosa?
Ciprofloxacin and levofloxacin
43
In which clinical scenarios would it be important to use a bactericidal vs. a bacteriostatic agent?
* 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
44
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?
* 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
45
Name two 3rd generation cephalosporins.
How are they different?
Ceftriaxone, ceftazidime
Ceftriaxone maintains some gram (+) activity
Ceftazidime does not have any gram (+) activity, and is **active against pseudomonas**
46
Which generation of cephalosporin is cefazolin?
What is it active against?
1st generation
* Good gram (+) coverage
* Strep, MSSA
* Some gram (-) coverage
* E. coli, K. pneumoniae, protius mirabilis
47
What is the minimum inhibitory concentration (MIC)?
The lowest concentration of an antibiotic that prevents visible growth of the organism after 18-24 hours of incubation
48
What is the general mechanism of lincosamide antibiotics?
Inhibit bacterial protein synthesis by binding the 50S subunit of bacterial ribosomes
49
What is the mechanism of tetracycline antibiotics?
Inhibit bacterial protein synthesis
Bind to the 30S bacterial ribosome
50
What does a live attenuated vaccine contain?
What is the efect on the host?
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
51
What are the mechanisms of resistance to tetracycline antibiotics?
* Protein pump acquisition/alteration
* Impaired influx of antibiotic
* Increased efflux of antibiotic
* Proteins that interfere with tetracycline/ribosome binding
* Enzyme inactivation
52
Which beta-lactam antibiotics provide the least gram-negative coverage?
Penicillin, oxacillin
(ampicillin only has minimal gram-negative activity)
53
What are the mechanisms of resistance of aminoglycoside antibiotics?
* 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
54
Which beta-lactam antibiotics are active against both gram-positive and gram-negative bacteria?
* Anti-pseudomonal penicillins
* Piperacillin
* Beta-lactam/beta-lactamase inhibitor combos
* Ampicillin/sulbactam
* Piperacillin/tazobactam
* Carbapenems
55
What is the mechanism of fluoroquinolone antibiotics?
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
56
Which bacteria pose the most urgent threats (as per the CDC) for antibiotic resistance?
*C. difficile*
Carbapenem-resistant enterobacteriaceae (CRE)
Drug-resistant *Neisseria gonorrhoeae*
57
What kind of antibiotic is carbapenem?
A beta-lactam; interferes with peptidoglycan synthesis
Offers broad spectrum coverage; not vulnerable to beta-lactamases
58
Under which circumstances would you prescribe gentamicin for a patient with a staph infection?
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
59
What does it mean for an antibiotic to be "concentration-dependent?"
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
60
What does it mean for an antibiotic to be "time-dependent?"
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
61
What are 4 of the most common antibiotic toxicities shared by several classes of antibiotics?
* Diarrhea
* Anaphylaxis
* Hepatotoxicity
* Dermatological toxicity
* Rash
62
Which two bacteria are the most likely causes of bacterial meningitis?
Streptococcus pneumoniae
Neisseria meningitidis
63
Which antibiotics act by inhibiting DNA synthesis?
* **Fluoroquinolones**
* Inhibit topoisomerase II and IV
* (Ciprofloxacin, moxifloxacin, levofloxacin)
* **Sulfamethoxazole-trimethoprim**
* ****Inhibit bacterial folic acid synthesis pathway
64
Which infections can be treated with oxazolidinones (ex: linezolid)?
Many gram (+) bacteria
* MRSA
* MSSA
* Streptococci
* Enterococci (including vancomycin resistant)
* Gram (+) anaerobic cocci
* Gram (+) rods
65
Is Dengvaxia (the vaccine for Dengue fever) recommended for everyone?
Why or why not?
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
What is the general mechanism of sulfonamide antibiotics?
Inhibit the folic acid pathway
This inhibits bacterial DNA synthesis
67
Describe the spectrum an clinical use of metronidazole
* 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
Why is the HPV vaccine recommended for everyone?
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
List the arguments against double coverage antibiotic prescription
* May promote antibiotic resistance
* Increased cost
* Increased potential for toxicity/adverse effects
* Antagonism is possible
70
What is the difference between Sabin's and Salk's poliovaccines?
Which one is given in the USA today?
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
What are the dosing recommendations for time-dependent antibiotics?
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
What is the general mechanism of beta lactam antibiotics?
Beta lactam antibiotics inhibit bacterial wall synthesis by bindig to penicillin-binding proteins in the bacteria and interfereing with peptidoglycan formation
73
List 3 aminoglycoside antibiotics
Gentamicin
Tobramycin
Amikacin
74
Which anatomic compartments are considered "protected sites?"
How is this relevant to antibiotic treatment?
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
What is the difference between a Kirby-Bauer test and an E-test?
* 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
What is a toxoid?
A chemically treated toxin that is no longer toxic but retains immunogenicity
Example: Diphtheria toxoid = vaccine that protects against diphtheria
77
Give some examples of macrolide antibiotics
* Azithromycin
* Clarithromycin
* Erythromycin
78
Which antibiotic is generally used to treat *Streptococus pyogenes?*
Penicillin;
Most strains are susceptible; *Streptococcus* spp. do not make beta-lactamase
79
How can gut flora be maintained or re-populated during and after the course of an antibiotic prescription?
* 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
How can you determine MIC breakpoint from a Kirby-Bauer test?
You can't
However, you can compare the diameter of the zone of inhibition to standard values for that antibiotic to determine susceptibility
81
Which cephalosporins are active against pseudomonas?
Ceftazidime (3rd)
Cefepime (4th)
82
What is the MIC breakpoint?
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
Which antibiotics are most closely associated with C. diff infection?
**B**acterial **V**acation **F**inds **C.**diff **S**pores
* **B**eta-lactamase inhibitor combinations
* **V**ancomycin
* **F**luoroquinolones
* **C**ephalosporins
* **S**ulfa-drugs
Note: all antibiotics except Metronidazole has the potential to cause a C. diff infection
84
What kind of vaccine is the HPV vaccine?
Who is it recommended for?
Fractional virus
Nonavalent virus-like particle that self-assembles
(with no viral DNA inside)
Recommended for everyone; prevents cancer
85
In general, which antibiotics are bactericidal?
Are there exceptions?
In general, **cell wall agents** are bactericidal
Exception: Aminoglycosides inhibit protein synthesis, but are also bactericidal
86
Describe a scenario in which therapeutic drug monitoring would be useful
* 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
What does it mean for an antibiotic to be bacteriostatic?
The antibiotic inhibits the **growth** of bacteria
Killing of the bacteria is dependent on the host immune system
88
Which toxicity is most commonly associated with Daptomycin?
Myopathy
89
What kind of vaccine is the varicella vaccine?
Live attenuated VZV
90
Which vaccine is recommended to prevent Herpes Zoster Virus?
Who is it recommended for?
**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
Which infections can be treated by aminopenicillins like ampicillin or amoxycillin?
Streptococci
| (Vulnerable to beta-lactamase)
92
Which generation of cephalosporin is cefepime?
What is it active against?
4th generation
* Good gram positive coverage
* Strep and MSSA
* Good gram negative coverage
* Enerobacteriacea
* Pseudomonas
93
What are the toxicities associated with metronidazole?
* 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
What does an inactivated virus contain?
What is the effect on the host?
* 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
What does it mean for an antibiotic to be bactericidal?
The antibiotic causes the death of the bacteria
(Killing does not depend on host factors)
96
Which infections can be treated by a glycopeptide (vancomycin)?
Gram (+) species only
* MSSA
* MRSA
* Streptococcus epidermidis
* Most enterococci (except those encoding VanA, which would make them resistant)
97
Which agents have activity against gram-positive bacteria?
* Beta-lactams
* Penicillins
* Cephalosporins
* Carbapenems
* **Not monobactams**
* Glycopeptides (Vancomycin)
* Trimethoprim-sulfamethoxazole
* Oxazolidinones (Linezolid)
* Lipopeptides (Daptomycin)
98
List the arguments in favor of "double coverage" antibiotic prescription
* 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
Which beta-lactam antibiotic is active against most gram negative bacteria?
Carbapenems
We want to "save" these; if a bacteria is resistant to carbapenem, we're kind of screwed
100
Which infections can be treated by natural penicillins?
* Streptococci
* Meningococci
* Some enterococci
* Penicillin-susceptible pneumococci
(Vulnerable to beta-lactamase)
101
What is the mechanism of action of macrolide antibiotics?
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
What is the difference between Dtap and Tdap?
* 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
What drives allergic reactions to beta-lactam antibiotics?
What does this mean for cross-reactivity?
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
In which clinical situations would you use daptomycin?
Why?
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
What kind of antibiotics are **-mycin**s or **-micin**s?
Aminoglycosides; inhibit the 30s subunit of the bacterial ribosome to inhibit protein synthesis
106
In which clinical situations would vancomycin be the best choice of antibiotic?
Why?
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
What is Steven-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)
Which antibiotic is it associated with?
Severe adverse reaction characterized by...
* Fever
* Mucocutaneous lesions
* Sloughing of the epidermis
Most commonly associated with trimethoprim-sulfamethoxazole
108
Which infections can be treated with anti-staphylococcal penicillins like oxacillin?
* MSSA
* Some streptococci
109
Which feature of the pathogenesis of bacterial meningitis makes the infection easier to treat?
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
Which organisms are later-generation cephalosporins most effective against?
Later generation cephalosporins provide **broader coverage, especially for gram (-) organisms.** Most maintain their coverage against gram (+) organisms
111
What are the major mechanisms that confer antibiotic resistance?
* 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
Which vaccines can initiate a cell-mediated immune response?
A. Live, attenuated vaccine
B. Inactivated vaccine
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
Give some examples of tetracycline antibiotics
* Doxycycline
* Minocycline
* (anything ending with -cycline)
114
What is the mechanism of action of metronidazole?
Metabolites of the antibiotic damage the DNA of bacteria
115
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?
1. Gram (+) microbes
2. Cephazolin (IV) or cephalexin (oral)
116
Which infections can be treated with lipopeptides (ex: daptomycin)
Gram (+) only, but wide range
* MSSA
* MRSA
* Strep, epidermidis (but not the causative agent of cellulitis)
* Most enterococci
117
What is a "post-antibiotic effect?"
The antibiotic keeps killing microbes even after the serum concentration has fallen below MIC
Exhibited by concentration-dependent antibiotics
118
What are the 4 methods by which bacteria gain antibiotic resistance?
* Horizontal
1. Transduction
2. Transformation
3. Conjugation
* Vertical
1. Spontaneous mutation
119
What does the pneumococcal vaccine contain?
Who is it recommended for?
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
How can C. diff infection be prevented?
List 2 ways
* Healthcare workers should clean their hands to prevent the spread of spores
* Don't prescribe antibiotics unless absolutely necessary
121
Which beta-lactam antibiotic has activity against MRSA?
Ceftaroline (4th generation cephalosporin)
122
Which bacteria should be covered by empiric antibiotic treatment of community-acquired pneumonia?
Which agent shoud you use?
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
Describe the general spectrum of fluoroquinolone antibiotics
Broad spectrum against gram-negative, gram-positive, and atypical organisms
124
What do you need to consider when choosing an antibiotic for empiric treatment of bacterial meningitis?
Which agents do you choose?
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
Describe the spectrum and clinical use of macrolide antibiotics
* 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
Describe the spectrum and clinical use of moxifloxacin
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
Which antibiotics inhibit bacterial Coenzyme-A?
Nitrofurantoin
128
Which generation of cephalosporin is ceftriaxone?
What is it active against?
3rd generation
* Reduced gram (+) coverage
* Still active against pneumococci, staphylococci
* Improved gram (-) coverage
* Citrobacter
* S. marscens
* Providencia
129
Which types vaccines are more likely to lose efficacy over time?
A. Live, attenuated vaccine
B. Inactivated vaccine
B. Inactivated vaccine
130
Which beta-lactamase is **not** active against gram positive bacteria?
Monobactams
131
What is the general mechanism of oxazolidinone antibiotics?
Inhibit bacterial protein synthesis
Bind the 23S ribosomal RNA in the 50S subunit
(unique binding site = no cross-resistance)
132
Describe the spectrum and clinical use of ciprofloxacin
Ciprofloxacin is a fluoroquinolone
* Spectrum
* Gram negative
* Pseudomonas
* Atypical
* Clinical uses
* Treat UTI (simple cystitis)
* Active against enterobacteriaceae
133
What is the mechanism of action of nitrofurantoin?
Inhibits bacterial coenzyme-A
* Interferes with carbohydrate metabolism and cell wall formation
134
Which antibiotics act by inhibiting the bacterial ribosome?
30S
* Tetracycline
* Aminoglycoside
50S
* Macrolide
* Clindamycin
* Erythromycin
* Linezolid (Binds 23S RNA)
* Chloramphenicol
135
Which antibiotics are concentration-dependent?
All beta-lactams
Linezolid
136
Which infections can be treated with trimethoprim-sulfamethoxazole?
* MSSA
* MRSA (most)
* Some *Streptococcus* spp.
* But NOT the causative agent of cellulitis
* Enterobacteriaceae
137
Which drugs are concentration and time-dependent?
Vancomycin
Daptomycin
Tetracycline
Macrolides
138
Which toxicity is most commonly associated with Linezolid?
Bone marrow suppression
139
What is the mechanism of aminoglycoside antibiotics?
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
Which organisms are first-generation cephalosporins most effective against?
Gram (+) bacteria
141
List 4 potential negative consequences of antibiotic use
* Toxicity
* Including allergic reactions
* C. diff infection
* Development of antibiotic resistance
* Disruption of the normal flora
* Can lead to vomiting, diarrhea, etc.
142
In a time-concentration curve, which measurement represents the total concentration of the drug?
Area under the curve (AUC)
143
Which agents are active against MRSA?
**L**ineman **T**ouch**D**own, **V**ery **C**ool
* 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
Describe the spectrum and clinical uses of tetracycline antibiotics
* 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
Describe the spectrum and clinical use of nitrofurantoin
* Spectrum
* Gram negative
* Enterobacteraciae
* E. coli
* Gram positive
* Staphylococcus saprophyticus
* Clinical use
* **Only used to treat UTI**
146
What vaccines are recommended for pregnant women?
* 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)*
## Footnote
**Do not give live, attenuated vaccines**
147
Describe the spectrum and clinical use of aminoglycoside antibiotics
* 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
Which vaccines are **NOT** recommended for pregnant and immunocompromised patients?
A. Live, attenuated vaccine
B. Inactivated vaccine
A. Live, attenuated vaccine
149
What are the 3 key parameters that determine the effect of an antibiotic on the bacterial population?
* EC50
* EMax
* H: The slope of the curve (aka Hill factor)
150
Which infections can be treated by beta-lactam/beta-lactamase inhibitor combos such as ampicillin/sulbactam or piperacillin/tazobactam?
* MSSA
* Streptococcus
* Anaerobic bacteria
* *E. coli*
Beta-lactamase inhibitor = can kill bacteria that make beta-lactamase!
151
What are the 4 major beta-lactam antibiotics?
Penicillins, Cephalosporins, Monobactams, Carbapenems
152
List 3 macrolide antibiotics
Azithromycin
Erythromycin
Clarithromycin
153
What are some features of tetracycline that make it an effective antibiotic?
* It is distributed widely to tissues
* Effective against intracellular bacteria
* Broad spectrum
154
Which generation of cephalosporin is ceftazidime?
What is it active against?
3rd generation
* No gram (+) coverage
* Improved gram (-) coverage
* Citrobacter
* S. marscens
* Providencia
155
Which class of antibiotics is associated with achilles tendon rupture?
Fluoroquinolones
156
What is the most worrisome toxicity related to macrolide antibiotics?
Cardiac
* Macrolides may prolong the QT interval and cause arrhythmia
* Toxicity is more likely in patients with coronary artery disease
157
Which toxicity is most commonly associated with Trimethoprim-sulfamethoxazole?
Stevens-Johnson syndrome
(Severe reaction characterized by fever, mucocutaneous lesions, sloughing of the epidermis)
158
Which toxicity is most commonly associated with Beta-lactams?
Allergic reactions/anaphylaxis
