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Flashcards in Antibacterial therapy Deck (74):
1

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

Orally....pretty same serum concentration is achieved as IV

2

When might Vd be increased

When ECFV is increased, as in heart failure

3

Antimicrobials that do NOT require renal adjustment

Azithromycin
Ceftriaxone
Clindamycin
Cloxacillin
Doxycline
Linezolid
Metronidazole
Moxifloxacin

4

MIC and MBC

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

5

Types of antimicrobial susceptibility testing

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

6

Bacteriostatic drugs are usually...
Bactericidal drugs are usually...

Protein synthesis inhibitors
Cell wall or DNA synthesis inhibitors

7

When would you use a bactericidal drug
When would you avoid bactericidal drugs

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

8

Examples of bactericidal drug classes

Beta lactams
Carbapenems
Fluoroquinilones
Aminoglycosides
Metroidazole
Glycopeptides
Lipopeptides

9

Examples of bacteriostatic drug classes

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

10

Post antibiotic effect

Continued inhibition of bacterial growth after the antimicrobial is discontinued

11

Factors in choosing an antimicrobial

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

12

Drug classes within beta-lactams

Penicillins
Cephalosporins
Carbapenems

13

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

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

14

Mechanisms of resistance to beta-lactams

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

15

PK/PD properties of beta-lactams

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

16

Spectrum of cephalosporins

NO activity vs. enterococci
NO activity vs. MRSA

17

Carbapenems are usually reserved for...

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

18

Glycopeptides MOA

Inhibit cell wall synthesis earlier than beta-lactams

19

Lipopeptides MOA

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

20

Glycopeptide/Lipopeptide spectrum

G+ (including MRSA)

21

Glycopeptide/Lipopeptide PK/PD

Bactericidal
Poor CSF penetration

22

Aminoglycoside MOA

Binds to 30S, inhibits protein synthesis

23

Aminoglycoside PK-PD

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

24

Macrolides MOA

Protein synthesis inhibtiion (50S)

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