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Antibacterial therapy Flashcards

1
Q

When drugs are greater than 80% bioavailable, how should you administer them?

A

Orally….pretty same serum concentration is achieved as IV

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2
Q

When might Vd be increased

A

When ECFV is increased, as in heart failure

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3
Q

Antimicrobials that do NOT require renal adjustment

A 
Azithromycin
Ceftriaxone
Clindamycin
Cloxacillin
Doxycline
Linezolid
Metronidazole
Moxifloxacin
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4
Q

MIC and MBC

A 
MIC= mininum inhibitory concentration is the lowest antimicrobial concentration that inhibits visible growth
MBC= minimum bactericidal concentration is the minimum concentration of antimicrobial needed to have bactericidal action

Both are determined with broth dilution. MIC can be determined with Epsilometer testing

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5
Q

Types of antimicrobial susceptibility testing

A 
Disk diffusion (yes/no)
Broth dilution (MIC and MBC)
E- test (MIC)
Synergy testing (synergistic vs. antagonistic effects)
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6
Q

Bacteriostatic drugs are usually…

Bactericidal drugs are usually…

A

Protein synthesis inhibitors

Cell wall or DNA synthesis inhibitors

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7
Q

When would you use a bactericidal drug

When would you avoid bactericidal drugs

A

Deep seated infections
vs.
inflammation from bacterial lysis is a danger

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8
Q

Examples of bactericidal drug classes

A 
Beta lactams
Carbapenems
Fluoroquinilones
Aminoglycosides
Metroidazole
Glycopeptides
Lipopeptides
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9
Q

Examples of bacteriostatic drug classes

A 
Macrolides
Clindamycin (Lincosamides)
Linezolid (Oxazolidinones)
Tetracyclines
Glycylcyclines
Anti-folates
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10
Q

Post antibiotic effect

A

Continued inhibition of bacterial growth after the antimicrobial is discontinued

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11
Q

Factors in choosing an antimicrobial

A

Efficacy: susceptibility of organism, infection site

Toxicity: interactions

Patient Factors: renal/hepatic function, weight, allergies, age, pregnancy, immune status

Ease of administration: PO vs. IV, once a day is easier than QID

Cost

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12
Q

Drug classes within beta-lactams

A

Penicillins
Cephalosporins
Carbapenems

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13
Q

Mechanism of action of beta-lactams and imitations of beta-lactams

A
  • Inhibit cell wall synthesis

- therefore, not active against mycoplasma (they lack a cell wall) and not active vs. intracellular pathogens

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14
Q

Mechanisms of resistance to beta-lactams

A
  • altered penicillin binding protein
  • alteration in channel in outer membrane needed to access cell wall (and PBP)
  • production of beta-lactamase
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15
Q

PK/PD properties of beta-lactams

A
  • Relatively poor bioavailability (need IV for serious infections)
  • Bactericidal
  • Wide distribution (incl. bone, and some CNS) with IV
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16
Q

Spectrum of cephalosporins

A

NO activity vs. enterococci

NO activity vs. MRSA

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17
Q

Carbapenems are usually reserved for…

A

multi-drug resistance (but not effective vs. MRSA)

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18
Q

Glycopeptides MOA

A

Inhibit cell wall synthesis earlier than beta-lactams

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19
Q

Lipopeptides MOA

A

cell wall membrane disruption (unique MOA means less chance of resistance)

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20
Q

Glycopeptide/Lipopeptide spectrum

A

G+ (including MRSA)

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21
Q

Glycopeptide/Lipopeptide PK/PD

A

Bactericidal

Poor CSF penetration

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22
Q

Aminoglycoside MOA

A

Binds to 30S, inhibits protein synthesis

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23
Q

Aminoglycoside PK-PD

A

Bactericidal
Only IV/IM
Poor CNS and bone penetration
Renal elimination

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24
Q

Macrolides MOA

A

Protein synthesis inhibtiion (50S)

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25
Macrolides PK/PD
Bacteriostatic Works agains intracellular organisms Poor bioavailability
26
Lincosamides MOA
Protein synthesis inhibition
27
Lincosamines PK/PD
Bacteriostatic Excellent bioavailability Penetrates bone, but not CSF or urine
28
Tetracyclines and glycylcyclines MOA
Protein synthesis inhibition
29
Tetracyclines and glycylcyclines PK/PD
Bacteriostatic Excellent bioavailability Active vs. intracellular pathogens
30
Fluoroquinolones MOA
Inhibition of DNA gyrase and topoisomerase
31
Fluroquinolones PK/PD
Bactericidal | Excellent bioavailability
32
Anti-folates MOA
Inhibit purine synthesis
33
Anti-folates PK/PD
Bacteriostatic | Excellent bioavailability
34
Nitroimidazoles MOA
Inhibits DNA synthesis
35
Nitroimidazole PK/PD
Excellent bioavailability | Excellent CNS penetration
36
Oxazolidinones MOA
Protein synthesis inhibition
37
Oxazolidinones PK/PD
Bacteriostatic Excellent bioavailability Excellent lung and CNS penetration
38
Anti-tuberculous MOA
Rifampin: inhibits mRNA synthesis Isoniazid: inhibits mycolic acid synthesis Pyrazinamide: inhibits mycolic acid synthesis Ethambutol: inhibits cell wall synthesis
39
How many people who report penicillin allergy have a true IgE mediated reaction?
10%
40
Is IgE-mediated penicillin allergy genetic?
No
41
Is IgE-mediated penicillin allergy permanent?
Not usually (80% lose sensitivity after 10 years)
42
Graded challenge vs. desensitization
A graded challenge is good for distant reactions. Give 1/10th or less of the dose and observe. Desensitization starts at a fraction of the therapeutic dose (1/100) and works up to therapeutic dose (AKA induction of drug tolerance)
43
Penicillin allergy cross-reactivity - chance with cephalosporins - chance with carbapenems
- 2.5% risk with cephalosporins with confirmed penicillin allergy. Better with later generations - 1% risk with carbapenems
44
Example of non-IgE mediated lief-threating allergy
Stevens-Johnson Syndrome (Type IV hypersensitivity)
45
Highest risk for subsequent C. diff infection
Cephalosporins Fluoroquinolones Clindamycin
46
Highest risk of increasing INR due to inhibition of Vit K producing bacteria
Septra Ciprofloxacin Metronidazole
47
Only useful for lower UTI
Nitrofurantoin
48
Concentration dependent killing, so can give high dose less often....
Fluoroquinolones | Aminoglycosides
49
CYP34A inhibitors
Clarithromycin | Anole antifungals
50
CYP34A inducers
Rifampin
51
Polyenes MOA
Bind to ergosterol
52
Polyenes PK/PD
Fungicidal, not renally eliminated
53
Azole MOA
inhibit ergosterol synthesis
54
Azole PK/PD
fungistatic vs. candida and fungicidal vs. aspergillus | Potent CYP 3A4 inhibitors
55
Echinocandins MOA
inhibit glucan synthesis
56
Echinocandins PK/PD
fungicidal vs. candida, fungistatic vs. aspergillus | Not renally eliminated
57
Allylamines MOA
inhibits squalene epoxidase (ergosterol synthesis)
58
Allylamines PK/PD
Dsitributes mainly to sebum and skin
59
Clotrimazole MOA
inhibit ergosterol synthesis
60
Ciclopirox MOA
inhibit cell uptake of substrates
61
Tolnaftate
inhibits squalene epoxidase (ergosterol synthesis)
62
Chloroquine MOA
inhibits HgB utilization by plasmodium
63
Mefloquine MOA
inhibts HgB utilization by plasmodium
64
Atovaquone/proguanil MOA
inhibit ETC in plasmodium
65
Artesunate MOA
free radicals
66
Qunine MOA
intercalates plasmodium DNA
67
Primaquine MOA
binds plasmodium DNA
68
Albendazole MOA
inhibits microtubule formation in helminths
69
Ivermectin MOA
activates chloride channels in helminths
70
Pyrantel pamoate MOA
cholinesterase inhbitor (in helminths only?)
71
Praziquantel MOA
increase schistome permeability to calcium
72
Iodoquinol MOA
unknown, antiprotozoal
73
Parmomycin MOA
bind 30S
74
Permethrin MOA
alters sodium channels, paralyses parasite

IDMM (33 decks)

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