Macrolides/Tetracyclines/Glycopeptides

Question 1

Macrolide Examples

Answer 1

Erythromycin
Clarithromycin
Azithromycin

Question 2

Macrolide MOA

Answer 2

attach to the 23S rRNA on the 50S subunit of bacterial ribosome resulting in

inhibition of protein synthesis

Question 3

Macrolide Killing??

Answer 3

Generally bacteriostatic; time dependent killing

Question 4

Bacteria resistance to macrolides

Answer 4

• Change to the binding site

methylation of the rRNA receptor
Inactivating enzymes (able to produce some enzyme that can mess with macrolide causing it to be inactive)
Active efflux (drug actively pumped out so cannot attach at the ribosome)

Question 5

Macrolides spectrum of activity

Answer 5

Gram positive – pneumococci, streptococci and corynebacteria (reserved for penicillin allergic patients)
M pneumoniae
Chlamydia trachomatis –> STI
C. pneumophilia
Bordatella pertussis –> Whooping cough (beta-lactams ineffective)
Campylobacter jejuni –> Stomach/gut
Helicobacter pylori –>Stomach/gut

Question 6

Erythromycin Route of Admin

Answer 6

IV or Oral

Question 7

Adverse Effects of Erythromycin

Answer 7

Gi

Increased liver function tests (LFTs)

Cholestatic hepatitis – increased with estolate and pregnancy (dark urine and jaundice)

Question 8

Drug Interaction Erythromycin

Answer 8

QT prolongation/cardiac arrhythmias particularly when combined with CYP 3A inhibitors –> Have to be alert for drug interactions

Question 9

Clarithromycin and Azithromycin Spectrum of Activity

Just Azithro covers……

Answer 9

Active against staph and strep

• Enhanced against:

L. pneumophilia (pneumonias) , Chlamydia trachomatis (STI), Chlaydiophila pneumoniae, Moraxella catarrhalis, H. influenzae (azithro), Mycobacterium avium complex and other mycobacteria

Question 10

Clarithromycin and Azithromycin are useful for some…..

Answer 10

MRSA

Question 11

Clarithromycin and Azithromycin have lower rates of….

Answer 11

G.I. adverse effects

Question 12

Azithromycin is unique because….

Answer 12

Long half-life leads to long intracellular concentrations

5 days of azithromycin = 10days of therapy

Long periods of sub-inhibitory concentrations may lead to more resistance

Question 13

Uses of Macrolides include…

Answer 13

Upper respiratory tract infections
Sexually transmitted infections
Acne –> effective

Question 14

Macrolide Drug Interactions. Which one has the least interactions?

Answer 14

Significant number of DI especially with erythromycin and clarithromycin

Fewer with azithromycin (if pt is on. A lot of meds)

Erythromycin and clarithromycin are substrates and inhibitors of CYP 3A4

Long list of drugs that are metabolized by CYP 3A4, so E or C may increase the toxicity

Antiarryhthmics, antidepressants, benzodiazepines, anticonvulsants, statins (very common), anticonvuslasants, etc

Question 15

Clindamycin MOA

Answer 15

same as macrolides

Question 16

Clindamycin Spectrum

Answer 16

anaerobes, S. aureus including some MRSA as well as streptococci

Question 17

Clindamycin Use. Is it the drug of choice for any infections? Why?

Answer 17

Used in patients with penicillin allergies or with resistant organisms
Not DOC for any infections
Oral or parenteral –> Can be used in serious and minor infections

Associated the most of antibiotic caused diarhhea  worst culprit of Clostridium difficile infection

Question 18

Clindamycin Adverse Effects and Counselling Tip

Answer 18

Nausea, vomiting, diarrhea
Rash
Elevated LFTs–> not the same degree of macrolides

Esophageal irritation –> pt. counselling –> always be taken with liquid or water –>sit upright after taking it for awhile

Associated with C. difficile diarrhea

Question 19

Tetracycline Examples

Answer 19

• tetracycline
• minocycline
• doxycycline

Question 20

Tetracycline MOA

Answer 20

inhibit binding of aminoacyl-tRNA to the 30S unit of ribosome thereby

inhibiting protein synthesis

Question 21

Tetracycline killing

Answer 21

• Bacteriostatic

Question 22

Tetracyclines spectrum of activity

Answer 22

active against many gram positive and negative organisms but high rates of resistance (e.g. E. coli, S. pneumoniae)

drugs of choice for rickettsiae, Bartonella, chlamydiae and M. pneumoniae
Nocardia –> less common
P. acnes

Question 23

Adverse Effects of Tetracyclines and Contraindications

Answer 23

Gi upset (N, V, D)
Skin rashes
Photosensitivity
Yeast overgrowth –> vaginitis, skin inf (moist places), mouth inf
Deposited in bones and teeth; do not use in children < 8 years old (can cause discolouration of teeth as well as bone deformities)
Hepatitis

Question 24

Tetracycline Drug Interactions + Counselling

Answer 24

Some anticonvulsants may reduce tetracycline levels ( phenobarbital, phenytoin, carbamazepine) –> May not get eves high enough to treat the infection
Divalent and trivalent cations reduce absorption ( iron, bismuth, calcium, magnesium, aluminum); separate doses
Counsel pt’s –> do not take with multivitamin
Doxyxycline has less binding to calcium so therefore do not need to counsel on not taking with milk, etc.
Increased INR and bleeding with warfarin –> Increased bleeding

Question 25

Glycylcyclines Example

Answer 25

Synthetic analogue of tetracycline – tigecycline

Question 26

Tigecycline Spectrum

Answer 26

Active against many gp and gn organisms including MRSA, S. pneumoniae and enterococci, Salmonella, Shigella and Acinetobacter; also anaerobes

Question 27

Tigecycline eliminated through... and are for...

Answer 27

Eliminated through biliary tract and feces Reserved for resistant organisms

Question 28

Glycopeptides Example

Answer 28

Vancomycin

Question 29

Glycopeptide MOA

Answer 29

– inhibits cell wall peptidoglycan synthesis - Bactericidal

Question 30

Glycopeptides resistance

Answer 30

- VRE, S. aureus (VISA)

Question 31

Vancomycin Spectrum

Answer 31

gpc in particular enterococci, PRSP (penicillin resistant streptococcus pneumonaie) and MRSA (pt who is very ill with MRSA); active against clostridia, Clostrioides and some bacilli

Question 32

Vancomycin is the DOC for

Answer 32

Vancomycin is the drug of choice for C. Diff Infection (any antibiotic can produce C. Diff but the more narrow the less chance of infection

Question 33

Vancomycin Route of Admin

Answer 33

IV for serious infections PO only for C. difficile; not orally absorbed

Question 34

Adverse Effects of Vancomycin

Answer 34

Nephrotoxicity – especially in combination with nephrotoxins --> damage to the kidneys Ototoxicity --> Manifests as hearing impairement; or imbalances (not usually) Red-man syndrome (red-neck syndrome) --> person turns red, uncomfortable, associated with hypotension, pt fees nauseated, flushed, uncomfortable --> can be reduced by reducing the infusion rate --> Need to keep in mind of infusion rate --> if to fast, every one will get RMS - 500 mg infused over an hour --> long infusion rates Granulocytopenia --> long term use