C.17. Glycopetides. Fusidans, Lipopetides. Bacitracin. Mupirocin. Pharmacotherapy of skin and soft tissue infection.

Question 1

what is the mechanism of action of Glycopeptides Ab?

Answer 1

1. Bactericidal effect
2. interfere with cross-linking. GP’s Binds at the D-ala-D-ala terminal –> inhibits the elongation of peptidoglycan chains

Question 2

list the Glycopeptide antibiotics

Answer 2

Vancomycin
Teicoplanin
Oritavancin
Mupirocin

Question 3

how are vancomycin, teicoplanin and Oritavancin given?

Answer 3

Parenterally

*not absorbed orally –> benefit in bacterial colitis treatment

Question 4

what strains are resistant to Vancomycin, teicoplanin and Oritavancin. what is the mechanism of resistance?

Answer 4

VRSA -vancomycin-resistant S. aureus
VISA- vancomycin intermediate S.aureus
VRE-vancomycin resistant Enterococci
most β-lactamases

alteration of the terminal D-ala to D-lactate

Question 5

what is the spectrum and clinical uses of Vancomycin and Teicoplanin? (6)

Answer 5

Narrow spectrum:

1. gram + bacteria
2. MRSA and PRSP
3. Clostridium difficile (2nd line)
4. empiric treatment: endocarditis, meningitis (with 3 gen’ cephalosporins)
5. osteomyelitis
6. prosthetic joint infection

Question 6

what is the spectrum and clinical uses of Oritavancin?

Answer 6

narrow spectrum:

1. gram + bacteria, anerobic and aerobic
2. severe skin infection

Question 7

what is the T1/2 of Vancomycin and teicoplanin?

Answer 7

6 hours

Question 8

do vancomycin and Teicoplanin require monitoring of drugs plasma concentrations?

Answer 8

yes, have a narrow therapeutic index

Question 9

adverse effects of Vancomycin and Teicoplanin?

Answer 9

chills, fever
injection site phlebitis
ototoxicity
nephrotoxicity (when given with aminoglycosides)
DRESS syndrome
diffuse flushing–>’red man syndrome’ when given rapid IV administration due to histamine release

Question 10

how do we avoid ‘red man syndrome’ when giving Vancomycin and Teicoplanin?

Answer 10

slow injection

Question 11

what is more toxic- vancomycin or Teicoplanin?

Answer 11

vancomycin

Question 12

side effects of Oritavancin?

Answer 12

GI symptoms
elevated liver enzymes
elevated CK

Question 13

what is the mechanism of Mupirocin

Answer 13

inhibits bacterial protein synthesis by selectively binding to isoleucyl-tRNA synthetase

Question 14

when do we give Mupirocin?

Answer 14

1. gram +cocci
2. impetigo caused by staph (MRSA), S.pyogenes
3. nasal carriage of S. Aureus (intranasal ointment)

Question 15

who do we give intranasal ointment Mupirocin for S. aureus nasal carriage?

Answer 15

medical workers

Question 16

how do we give Mupirocin?

Answer 16

topically (not absorbed)

Question 17

side effects of Mupirocin

Answer 17

local itching and burning

rash, erythema, contact dermatitis

Question 18

what is Daptomycin?

Answer 18

Lipopeptide Ab

depolarization agent

Question 19

what is the mechanism of action of Daptomycin

Answer 19

Bactericidal effect

enters the cytoplasmic membrane (irreversibly)–> disrupts ionic gradients and membrane depolarization

Question 20

what has a more rapid effect- daptomycin or vancomycin?

Answer 20

daptomycin

Question 21

what is the spectrum of daptomycin?

Answer 21

narrow
gram +
MRSA,VRSA ,VRE

Question 22

How is daptomycin given?

Answer 22

parenterally

Question 23

how is daptomycin eliminated in the body?

Answer 23

renal

Question 24

what inhibits daptomycin and when it shouldn’t be given?

Answer 24

pulmonary surfactant

cannot be used to treat pneumonia

Question 25

side effects of daptomycin

Answer 25

myopathy (additive with statins)--> monitor creatine phosphokinase Rhabdomyolysis (rare) pneumonitis (therapy >2 w')

Question 26

what Ab are polypeptides?

Answer 26

bacitracin and fusidic acid

Question 27

is Bacitracin bacteriostatic or bactericidal?

Answer 27

both (depends on the concentration)

Question 28

how is Bacitracin given?

Answer 28

topically (wounds) | too toxic for systemic use --> nephrotoxicity

Question 29

what does bacitracin do?

Answer 29

inhibits the precursor translocation across the bacterial membrane

Question 30

what is Neomycin-Bacitracin- Polymyxin B?

Answer 30

ointment preparation, over the counter drug (Neosporin) | prevent and treat minor skin infection

Question 31

how is fusidic acid given?

Answer 31

topical/parenteral

Question 32

when do we give systemic fusidic acid (fusidans)?

Answer 32

MRSA infection

Question 33

when do we give topical fusidic acid?

Answer 33

skin infection (cellulitis, impetigo), conjunctivitis

Question 34

what other indications are there for fusidic acids, other than skin infections are MRSA?

Answer 34

gram + aerobes and anaerobes corynebacterium endocarditis

Question 35

what is the mechanism of fusidic acids (fusidans)?

Answer 35

bacteriostatic effect | inhibitor of bacterial protein synthesis (inhibits translocations-elongation factor G)

Question 36

what side effect does fusidic acid cause in systemic use?

Answer 36

hepatotoxicity

Question 37

what is the 1st line topical treatment for Cellulitis &impetigo?

Answer 37

fusidic acid Mupirocin Polymyxin E (colistin)

Question 38

what is the 1st line treatment for Cellulitis &impetigo in case of staphylococcal or streptococcal infection?

Answer 38

Nafcillin IV or Oxacillin IV

Question 39

what is the alternative treatment for Cellulitis &impetigo in case of staphylococcal or streptococcal infection?

Answer 39

Cefazolin IV or | Ampicillin/Sulbactam IV

Question 40

what is the 1st line treatment for Cellulitis &impetigo in case of MRSA infection?

Answer 40

vancomycin IV

Question 41

what is the alternative treatment for Cellulitis &impetigo in case of MRSA infection?

Answer 41

Linezolid IV

Question 42

what is the 1st line treatment for Necrotizing fasciitis?

Answer 42

Clindamycin IV and Penicillin-G IV

Question 43

what is the 1st line treatment for gas gangrene (C.perfringes)?

Answer 43

Clindamycin IV and Penicillin-G IV

Question 44

what is the alternative treatment for Necrotizing fasciitis?

Answer 44

Clindamycin IV and Cephalosporin IV

Question 45

what is the alternative treatment for gas gangrene (C.perfringes)?

Answer 45

Clindamycin IV and Cefoxitin IV