C17. Glycopeptides. Fusidans. Lipopeptides. Bacitracin. Mupirocin. Pharmacotherapy of skin and soft tissue infections. Flashcards
What spectrum does Lipopeptides cover?
It has a similar spectrum to vancomycin → Gram + microbes (Staph, Strep, Enterococcus) but also affects many vancomycin-resistant strains (VRE, etc.).
What is the MOA of Glycopeptides?
- Glycopeptides inhibit cell wall synthesis by binding to the D-Ala-D-Ala terminus of growing PG peptides.
- Altered PBPs of MRSA, etc. have no effect on this mechanism.
- Also resistant to beta-lactamases.
- Synergistic effect with aminoglycosides - help them cross the cell wall.
- Time-dependent and bactericidal effects.
What is the MOA of Fusidic Acid?
Fusidic Acid is one of the fusidans. It binds ribosome, unsure which subunit.
What are the side effects of Fusidic acid?
If systemic admin → GI and hepatotoxic.
What is the MOA of Bacitracin?
Bacitracin inhibits carrier in transfer of peptidoglycan subunits.
What is the MOA of Mupirocin?
Mupirocin is a protein synthesis inhibitor.
What spectrum does bactracin cover and its indication ?
Mainly covers Gram+ and is used for mixed skin infections.
What are the side effects of Bactracin?
It is high nephrotoxicity → local only.
What are the indications of Mupirocin and what spectrum does it cover?
It covers Gram+ cocci (Staph, incl. MRSA) and is used for minor skin infections (impetigo) or tx of Staph carriers.
What are the indications for Fusidic acid and what spectrum does it cover?
- For Gram + bacteria (Staph, incl. MRSA) and Corynebacteria.
- Used in skin infections by Gram + bacterias.
What is the route of administration of Fusidic acid?
- It can be given orally, but not normally.
- Usually given as a cream.
What are the side effects of Vancomycin?
- Red Man Syndrome - mast cell histamine release → flushing, hypotension; avoided with slower infusion
- (thrombophlebitis at injection site - reason for IM contraindication)
- (DRESS syndrome - rare).
What spectrum does glycopeptides cover?
- Narrow-spectrum against Gram-positive anaerobes and aerobes
- Enterococci, Diphtheroids, Listeria, Bacillus anthracis and Clostridia
- Staph incl. MRSA, Strep incl. penicillin-resistant Pneumococci (PRSP) should NOT use if it’s a non-resistant Staph/Strep
What is the resistance mechanism behind Glycopeptide resistance in bacteria?
- Binding Site Modification
- ex: VRE or VRSA or VISA (vancomycin-insensitive SA) microbe replaces terminal D-Ala with D-lactate → no binding.
What are the pharmacokinetic parameters like for Glycopeptides?
- only cross BBB in case of inflammation (ie meningitis)
- enters other compartments well (peritoneum, pleura)
- 90% excreted via kidney (must monitor plasma levels in renal patients)
What are the side effects of Glycopeptides?
Low risk nephro- / ototoxicity ( ↑ risk in pt with pre-impaired kidney function, elderly, or with other nephrotoxic drugs, such as aminoglycosides).
What are the indications for Glycopeptide?
- Severe infections (MRSA endocarditis/osteomyelitis, sepsis, post-op infection)
- Meningitis caused by pneumococci
- C. diff colitis - given orally
- (Nosocomial infections - Staph epidermidis endocarditis or MRSA pneumonia)
What are the pharmacokinetic parameters of Vancomycin?
- Normally ist is only given by IV admin, because it is not absorbed orally + irritates if given IM.
- The only exception to the rule is that it is given orally for C. diff colitis.
- (Good CNS penetration in inflammation → given with ceftriaxone for meningitis
- (good bone penetration for MRSA osteomyelitis)
What are the indications for Teicoplanin?
Teicoplanin is more effective than vancomycin and is used for vancomycin-resistant strains.
What is Ortiavancine used for?
Ortiavancine is a semi-synthetic and give as a single dose for C. diff colitis.
What is the route of administration of teicoplanin?
It is given IM or IV lower nephrotoxicity risk.
What are the indications of Vancomycin?
- C.diff colitis
- Given with ceftriaxone for meningitis
- MRSA osteomyelitis
What is the MOA of Lipopeptides?
Lipopeptides insert lipid tails into cell membrane causing depolarization + cell death (bactericidal).
What are the indications of Daptomycin?
- Nosocomial UTI or endocarditis caused by VRE
- infections caused by MRSA or VRSA (skin infections, etc. and especially bacteremia → endocarditis).
What are the contraindications of Daptomycin?
Contraindicated in S. aureus pneumonia (due to antagonism by surfactant).
What are the side effects of Daptomycin?
Myopathy and rarely rhabdomyolysis - monitor creatine kinase in prolonged tx.
