Pogue: Antimicrobials IIb Flashcards Preview

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1

Macrolides

MOA:

Bacteriostatic or Bactericidal?

Bind to the 50S subunit of the ribosome

Bacteriostatic

2

Macrolides

Agents (of clinical relevance)

Erythromycin (IV/PO)
Clarithromycin (PO)
*Azithromycin (IV/PO)*

3

Macrolides

Spectrum of activity

The respiratory pathogens

C.trachomatis: causes Chlamydia

Mycobacterium avium complex (MAC)

H.pylori: clarithromycin

4

The respiratory pathogens:

Streptococcus
H.influenzae
M.catarrhalis
Mycoplasma pneumonia
Chlamydia pneumonia
Legionella pneumophilia

5

What treats against MAC?

Mycobacterium avium complex (MAC): clarithromycin and azithromycin

6

What treats H.pylori?

Clarithromycin

7

Macrolides

Side effects
Biggest class concern:
Worst with what? Why?
Much less with what?

Biggest class concern: nausea/vomiting/diarrhea

–Worst with erythromycin as it binds to the motolin receptor in the GI tract
•Pearl: erythromycin actually used as promotility agent in hospital for severe constipation

–Much less with azithromycin

8

Macrolides

Other side effects:

QT prolongation (pro-arrhythmia)
Rare hepatotoxicity

9

Macrolides
Clinical Uses:

Respiratory Tract Infections: azithromycin first line for CAP (also used in traceobronchitis, COPD exacerbations)

H.pylori: clarithomycin part of standard therapy

Mycobacterial regimens: clarithromycin and azithromycin

10

Macrolide Resistance:

Target-Site Modification: change in the 50S subunit binding site

Decreased Concentration in the Cell: efflux pumps

11

Macrolide

IV dose =
Azithromycin half life:
Metabolism
DDIs
Renal dosing

IV dose = PO dose
Azithromycin long half-life
–~ 72 hours; allows shorter course of the drug

Metabolism
–Inhibitors and substrates of CYP3A4

Many drug interactions

No renal dose adjustment needed

12

Macrolide

DDIs:

Erythromycin and clarithromycin are the big players here

Azithromycin much less

Why azithromycin is the workhorse for this class

13

What is first line medication for CAP?

Azithromycin

14

What are ketolides?
What is Telithromycin?

Ketolides are antibiotics belonging to the macrolide group

Telithromycin is the first ketolide antibiotic to enter clinical use and is sold under the brand name of Ketek.

15

Ketolides: Telithromycin

General:

Spectrum of Activity:

Clinical Use:

Derivative of macrolides

Spectrum of Activity:
- Similar to azithromycin, with enhanced activity against S.pneumo

Clinical Use:
- Originally thought to be a niche drug for CAP
- High rates of hepatotoxicity has limited use clinically

16

TETRACYCLINES:

MOA:

Bacteriostatic or Bactericidal?

MOA: ribosomal antibiotic that works on the 30S subunit of the ribosome

Bacteriostatic

17

TETRACYCLINES:

Pharmacokinetics:

Highly lipophilic: penetrates tissues well

Not highly renally eliminated: but still sufficient for UTI

18

Tetracycline Agents (3):

What is used for SIADH?

Tetracycline (PO)

Doxycycline and Minocycline (IV/PO): most often used

Demeclocycline (PO): used for SIADH

19

Doxycylin and Minocycline

Spectrum of activity:
G+
G-
Anaerobic activity
Miscellaneous: has activity against (2)

Gram (+) Activity:
S.pneumo
S.aureus (including MRSA)
enterococcus

Gram (-) Activity:
H.influenzae
M.catarrhalis
may also have activity against enterobacteraciae (including MDRO)

Anaerobe Activity: variable

Miscellaneous: has activity against
o Atypical pneumonia pathogens
o Organisms associated with animal bites (Lyme disease)

20

Clinical Use (Doxycyclin and Minocyclin) (3):

Respiratory tract infections (including CAP)

UTIs

Skin and soft tissue infections (particularly when community acquired-MRSA is a concern)

21

Tetracycline
Adverse Effects (3):

N/V/D: lessened with food

Binding to growing teeth and bones: avoid if less than 8 years old

Photosensitization

22

Tetracycline
Drug Interactions:

Chelate with divalent and trivalent cations

Do not take with multivitamins!

23

What are Glycylcyclines?
What is Tigecycline?

Glycylcyclines are a new class of antibiotics derived from tetracycline.

Tigecycline is a glycylcycline antibiotic

24

Tigecycline:

MOA:

Pharmacokinetics:

First in this new class that is a derivative of the tetracyclines

MOA: same as tetracycline (bind 30S subunit of ribosome); also bacteriostatic (?)
o However, has a different structure and has the ability to overcome some of the tetracycline-resistance mechanisms (efflux pumps, target-site alterations)

Pharmacokinetics:
- Same as tetracycline

25

Tigecycline

Spectrum of Activity:
G+
G-
Anaerobic
Notable holes

Gram (+) Activity: broad (includes MRSA and VRE)

Gram (-) Activity: similar to tetracyclines, but also includes resistant organisms (ESBL, Acinetobacter)

Anaerobic Activity: some coverage

Notable Holes: pseudomonas and proteus (and providencia)

26

Tigecycline

Clinical use (3):

Adverse reactions:

Clinical Use:

Last line option for many nasty Gram (-) bugs:
o Carbapenem-resistant acinetobacter
o Klebsiella

Polymicrobial wounds: including MRSA or VRE

2nd line therapy for pts with penicillin allergies for multiple disease states

Adverse Reactions:
- Nausea and vomiting: 20% of patients
- Pancreatitis: few cases noted in post marketing analysis

27

LINCOSAMIDES

MOA:

Bacteriostatic or Bactericidal?

Agents (2):

Acts on 50S subunit of the ribosome to prevent protein synthesis

Bacteriostatic

Lincosamide Agents:
1. Lincomycin: been completely replaced by clindamycin (increased activity)
2. Clindamycin

28

Spectrum of Activity (Clindamycin):

G+
G-
Anaerobes

Gram (+) Activity: S.aureus (including MRSA), Streptococcus (usually)
o Note: has toxin suppression activity and necrotizing Gram (+) infections

Gram (-) Activity: NONE

Anaerobes: good (better for oral anaerobes than lower GI anaerobes)

29

Clinical Uses (Clindamycin) (3):

Skin infections: because of staphylococcus (including MRSA) and streptococcus coverage

Aspiration pneumonia: since anaerobes are thought to play a role (but NO Gram (-) coverage)

Alternative for anaerobic coverage

30

Side Effects (Clindamycin):

Diarrhea: in both PO and IV formulations

Nausea

C.difficile Diarrhea: used to be the number one antibiotic associated with C.diff (now FQ and other broad spectrum agents)