Antibiotics/Vaccines Flashcards
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 interfering with peptidoglycan formation
3
Q
What is the general mechanism of tetracycline antibiotics?
A
Inhibit the 30s 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 50s bacterial ribosome
6
Q
What is the general mechanism of oxazolidinone antibiotics?
A
Inhibit the 50s bacterial ribosome
7
Q
What is the general mechanism of lincosamide (clindamycin) antibiotics?
A
Inhibit the 50s bacterial ribosome
8
Q
What is the general mechanism of rifampin antibiotics?
A
Inhibit DNA-dependent RNA polymerase
9
Q
What is the general mechanism of sulfonamide antibiotics?
A
Inhibit the folic acid pathway (folate antagonist)
10
Q
Which antibiotic is generally used to treat Streptococus pyogenes?
A
Penicillin;
Most strains are susceptible
11
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)
12
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
13
Q
What kind of antibiotics are -floxacins?
A
Fluoroquinolones;
They directly inhibit bacterial DNA synthesis
14
Q
What kind of antibiotics are -mycins or -micins?
A
Aminoglycosides; inhibit the 30s subunit of the bacterial ribosome to inhibit protein synthesis
15
Q
What kind of antibiotic is carbapenem?
A
A beta-lactam; interferes with peptidoglycan synthesis
16
Q
What are the 4 major beta-lactam antibiotics?
A
Penicillins, Cephalosporins, Monobactams, Carbapenems
17
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
18
Q
What is an example of a broad spectrum beta-lactam with both gram-positive and gram-negative coverage?
A
Piperacillin-tazobactam
19
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
20
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)
21
Q
What is an example and the mechanism of action of glycopeptides?
A
vancomycin
Inhibit bacteria cell wall synthesis by binding to D-alanyl-D-alanine terminus and blocking linkage to glycopeptide polymer
22
Q
What is an example of a lincosamide antibiotic?
A
Clindamycin
23
Q
What is the mechanism of action of lincosamides (clindamycin)?
A
Inhibits protein synthesis by binding to the 50s subunit of the ribosome and blocking peptide bond formation
24
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
25
What is the mechanism of action of lipopeptides (daptomycin)?
1. Bind to cell membrane
2. Cause depolarization due to K+ efflux
3. Depolarization disrupts cellular processes and leads to cell death
26
What are the mechanisms of bacterial resistance to fluoroquinolones (ciprofloxacin, moxifloxacin, levofloxacin)?
* 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
27
What is the mechanism of action of nitrofurantoin?
* Inhibits bacterial Acetyl-CoA, interfering with carbohydrate metabolism
* Disrupts bacterial cell wall formation
28
What are examples of aminoglycosides?
* Gentamicin
* Amikacin
* Tobramycin
* Streptomycin
* Neomycin
29
What is the mechanism of action of aminoglycosides?
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
30
When can a drug be used while considering MIC and breakpoint?
When MIC is under the breakpoint
(ideally want MIC as far from breakpoint as possible)
31
What is the mechanism of action of tetracyclines?
Inhibiting protein synthesis by binding reversibly to the 30S ribosome
32
What are the uses/spectrum of tetracyclines?
* 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)
33
What is does it mean if an antibiotic acts by concentration-dependent killing?
The rate of bactericidal killing is mazimized at the peak concentration (Cmax) in the serum
34
For an antibiotic that acts by concentration-dependent killing, what occurs after drug concentrations decrease to levels below the MIC?
Persistent suppression of growth
due to post-antibiotic effect (PAE)
35
Which classes of antibiotics act by concentration-dependent killing?
* Aminoglycosides
* Fluoroquinolones
36
What does it mean if an antibiotic acts by time-dependent killing?
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%)
37
For an antibiotic that acts by time-dependent killing, what is the effect of achieving high peak serum concentrations?
For an antibiotic that acts by time-dependent killing, achieving high peak serum concentrations has no effect upon bacterial killing
38
What class of antibiotics acts by time-dependent killing?
Beta-lactams
| (also Linezolid)
39
What two drugs is therapeutic drug monitoring usually used for?
* Vancomycin
* Gentamicin (aminoglycosides)
40
In general, which antibiotics are bactericidal?
Cell-wall active agents
41
In general, which antibiotics are bacteriostatic?
Antibiotics that inhibit protein synthesis (except aminoglycosides)
42
What conditions is it optimal to use bactericidal antibiotics for?
* Septic shock
* Meningitis
* Endocarditis
* Impaired immune system
* Chemotherapy-induced neutropenia with infection
43
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
All the above!
44
What is the best choice for an antibiotic to treat C. difficile infection?
**Oral** vancomycin (or can do metro)
45
Which type of bacteria/pathogens does metronidazole target?
Anaerobes: all anaerobic cocci and both gram-negative bacilli, including Bacteroides spp., and anaerobic spore-forming Gram-positive bacilli
Protozoa: trichomonas, giardiasis, and amebiasis
46
What is the mechanism of action of macrolides (erythromycin, clarithromycin, azithromycin)?
Inhibiting protein synthesis by binding to the 50S subunit of the ribosome and blocking peptide bond formation
47
What is the spectrum of coverage of macrolides (erythromycin, clarithromycin, azithromycin)?
* Gram-positive: S. pneumoniae
* Gram-negative: H. influenzae, Neisseria spp., B. pertussis, Campylobacter
* Atypical: Mycoplasma, Legionella, Chlamydia
48
What is the toxicity of macrolides (erythromycin, clarithromycin, azithromycin)?
* GI, especially diarrhea
* Cardiac toxicity: prolonged QT interval leading to torsades des pointes, ventricular tachycardia, and sudden death
49
What are the toxicities of beta-lactams?
* Allergic reactions
* Anaphylaxis
50
What is the toxicity of aminoglycosides?
Nephrotoxicity
51
What is the toxicity of vancomycin?
Red Man's Syndrome
(histamine is released and skin becomes itchy upon vancomycin infusion)
52
What is the toxicity of fluoroquinolones?
Achilles tendon rupture
53
What is the toxicity of linezolid?
Bone marrow suppression
54
What is the toxicity of trimethoprim-sulfamethoxazole?
Stevens-Johnson Syndrome
55
Which agents have activity against gram-positive bacteria?
* Beta-lactams
* Penicillins
* Cephalosporins
* Carbapenems
* **Not monobactams**
* Glycopeptides (Vancomycin)
* Trimethoprim-sulfamethoxazole
* Oxazolidinones (Linezolid)
* Lipopeptides (Daptomycin)
56
Which beta-lactam is **not** active against gram positive bacteria?
Monobactams
57
Which penicillins are active against Staphylococcus spp?
Which are not?
Active against staph (not vulnerable to beta-lactamase)
* Anti-staphylococcal penicillins (oxacillin)
* Beta-lactam/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.
58
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
59
Are anti-staphylococcal penicillins active against MRSA?
Why or why not?
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
60
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)
61
Which infections can be treated by natural penicillins?
* Streptococci
* Meningococci
* Some enterococci
* Penicillin-susceptible pneumococci
(Vulnerable to beta-lactamase)
62
Which infections can be treated by aminopenicillins like ampicillin or amoxycillin?
Streptococci
| (Vulnerable to beta-lactamase)
63
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!
64
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)
65
Which infections can be treated with trimethoprim-sulfamethoxazole?
* MSSA
* MRSA (most)
* Some *Streptococcus* spp.
* But NOT the causative agent of cellulitis
* Enterobacteriaceae
66
Which infections can be treated with oxazolidinones (ex: linezolid)?
Many gram (+) bacteria
* MRSA
* MSSA
* Streptococci
* Enterococci (including vancomycin resistant)
* Gram (+) anaerobic cocci
* Gram (+) rods
67
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
68
What is a broad spectrum antibiotic?
Give some examples
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
69
Give 1-2 examples of cephalosporins from each generation
* 1st generation
* Cefazolin
* 2nd generation
* Cefuroxime
* 3rd generation
* Ceftriaxone
* Ceftazidime
* 4th generation
* Cefepime
70
Describe the general spectrum of fluoroquinolone antibiotics
Broad spectrum against gram-negative, gram-positive, and atypical organisms
71
Which fluoroquinolones are active against pseudomonas aeruginosa?
Ciprofloxacin and levofloxacin
72
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
73
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**
74
Which antibiotics act by inhibiting the bacterial ribosome?
30S
* Tetracycline
* Aminoglycoside
50S
* Macrolide
* Clindamycin
* Linezolid (Binds 23S RNA)
* Chloramphenicol
75
Which beta-lactam antibiotic provides the most comprehensive gram-negative coverage?
Carbapenems
(Cefepime, piperacillin/tazobactam, aztreonam, ceftazidime are also pretty good against most enterobacteriaceae and pseudomonas)
76
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 -)
Treatment = one of the following
* Fluoroquinolone w/ Gram negative coverage
* Ceftriaxone, ceftazidime, **cefipime**
* Doxycycline (a tetracycline)
* Azithromycin (a macrolide)
77
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
78
Which vaccines are **NOT** recommended for pregnant and immunocompromised patients?
A. Live, attenuated vaccine
B. Inactivated vaccine
A. Live, attenuated vaccine
79
What kind of vaccine is the measles vaccine?
Live attenuated vaccine
80
What kind of vaccine is the varicella vaccine?
Live attenuated VZV
81
Which vaccine is recommended to prevent Herpes Zoster Virus?
Who is it recommended for?
**Shingrix:** 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)
82
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)
83
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
84
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
85
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
86
What kind of vaccine is the HiB vaccine?
Why is it important?
conjugate polysaccaride
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
87
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**
