C17. Glycopeptides. Fusidans. Lipopeptides. Bacitracin. Mupirocin. Pharmacotherapy of skin and soft tissue infections.

Question 1

What spectrum does Lipopeptides cover?

Answer 1

It has a similar spectrum to vancomycin → Gram + microbes (Staph, Strep, Enterococcus) but also affects many vancomycin-resistant strains (VRE, etc.).

Question 2

What is the MOA of Glycopeptides?

Answer 2

1. Glycopeptides inhibit cell wall synthesis by binding to the D-Ala-D-Ala terminus of growing PG peptides.
2. Altered PBPs of MRSA, etc. have no effect on this mechanism.
3. Also resistant to beta-lactamases.
4. Synergistic effect with aminoglycosides - help them cross the cell wall.
5. Time-dependent and bactericidal effects.

Question 3

What is the MOA of Fusidic Acid?

Answer 3

Fusidic Acid is one of the fusidans. It binds ribosome, unsure which subunit.

Question 4

What are the side effects of Fusidic acid?

Answer 4

If systemic admin → GI and hepatotoxic.

Question 5

What is the MOA of Bacitracin?

Answer 5

Bacitracin inhibits carrier in transfer of peptidoglycan subunits.

Question 6

What is the MOA of Mupirocin?

Answer 6

Mupirocin is a protein synthesis inhibitor.

Question 7

What spectrum does bactracin cover and its indication ?

Answer 7

Mainly covers Gram+ and is used for mixed skin infections.

Question 8

What are the side effects of Bactracin?

Answer 8

It is high nephrotoxicity → local only.

Question 9

What are the indications of Mupirocin and what spectrum does it cover?

Answer 9

It covers Gram+ cocci (Staph, incl. MRSA) and is used for minor skin infections (impetigo) or tx of Staph carriers.

Question 10

What are the indications for Fusidic acid and what spectrum does it cover?

Answer 10

1. For Gram + bacteria (Staph, incl. MRSA) and Corynebacteria.
2. Used in skin infections by Gram + bacterias.

Question 11

What is the route of administration of Fusidic acid?

Answer 11

1. It can be given orally, but not normally.
2. Usually given as a cream.

Question 12

What are the side effects of Vancomycin?

Answer 12

1. Red Man Syndrome - mast cell histamine release → flushing, hypotension; avoided with slower infusion
2. (thrombophlebitis at injection site - reason for IM contraindication)
3. (DRESS syndrome - rare).

Question 13

What spectrum does glycopeptides cover?

Answer 13

1. Narrow-spectrum against Gram-positive anaerobes and aerobes
2. Enterococci, Diphtheroids, Listeria, Bacillus anthracis and Clostridia
3. Staph incl. MRSA, Strep incl. penicillin-resistant Pneumococci (PRSP) should NOT use if it’s a non-resistant Staph/Strep

Question 14

What is the resistance mechanism behind Glycopeptide resistance in bacteria?

Answer 14

1. Binding Site Modification
2. ex: VRE or VRSA or VISA (vancomycin-insensitive SA) microbe replaces terminal D-Ala with D-lactate → no binding.

Question 15

What are the pharmacokinetic parameters like for Glycopeptides?

Answer 15

1. only cross BBB in case of inflammation (ie meningitis)
2. enters other compartments well (peritoneum, pleura)
3. 90% excreted via kidney (must monitor plasma levels in renal patients)

Question 16

What are the side effects of Glycopeptides?

Answer 16

Low risk nephro- / ototoxicity ( ↑ risk in pt with pre-impaired kidney function, elderly, or with other nephrotoxic drugs, such as aminoglycosides).

Question 17

What are the indications for Glycopeptide?

Answer 17

1. Severe infections (MRSA endocarditis/osteomyelitis, sepsis, post-op infection)
2. Meningitis caused by pneumococci
3. C. diff colitis - given orally
4. (Nosocomial infections - Staph epidermidis endocarditis or MRSA pneumonia)

Question 18

What are the pharmacokinetic parameters of Vancomycin?

Answer 18

1. Normally ist is only given by IV admin, because it is not absorbed orally + irritates if given IM.
2. The only exception to the rule is that it is given orally for C. diff colitis.
3. (Good CNS penetration in inflammation → given with ceftriaxone for meningitis
4. (good bone penetration for MRSA osteomyelitis)

Question 19

What are the indications for Teicoplanin?

Answer 19

Teicoplanin is more effective than vancomycin and is used for vancomycin-resistant strains.

Question 20

What is Ortiavancine used for?

Answer 20

Ortiavancine is a semi-synthetic and give as a single dose for C. diff colitis.

Question 21

What is the route of administration of teicoplanin?

Answer 21

It is given IM or IV lower nephrotoxicity risk.

Question 22

What are the indications of Vancomycin?

Answer 22

1. C.diff colitis
2. Given with ceftriaxone for meningitis
3. MRSA osteomyelitis

Question 23

What is the MOA of Lipopeptides?

Answer 23

Lipopeptides insert lipid tails into cell membrane causing depolarization + cell death (bactericidal).

Question 24

What are the indications of Daptomycin?

Answer 24

1. Nosocomial UTI or endocarditis caused by VRE
2. infections caused by MRSA or VRSA (skin infections, etc. and especially bacteremia → endocarditis).

Question 25

What are the contraindications of Daptomycin?

Answer 25

Contraindicated in S. aureus pneumonia (due to antagonism by surfactant).

Question 26

What are the side effects of Daptomycin?

Answer 26

Myopathy and rarely rhabdomyolysis - monitor creatine kinase in prolonged tx.