Gylycopeptides (3)
Teicoplanin
Oritavacin
Vancomycin
Glycopeptides MOA
- Bactericidal glycoprotein
- Bind to d-Ala-d-Ala terminal of peptidoglycan –> inhibit transglycosylation –> prevent elongation of the peptidoglycan chain and interferes with cross-linking.
Glycopeptide resistance development
give examples
- bacterial replacement of the terminal d-Ala by d-lactate –> vancomycin binding site affinity is decreased
- VRE and VRSA
Glycopeptides indications
- Narrow spectrum
- used for serious infections by G+’s (ex.MRSA)
- used in combination with 3rd Gen. Cephalo. (ex. Ceftriaxon) against PRSP
- used against C.difficile
Glycopeptides Pharmacokinetics
- when given orally not absorbed by the G.I.
- when given parenterally –> penetrates most tissues
- eliminated unchanged in the urine
Glycopeptides administration
- Orally (bacterial enterocolitis)
- Parenterally
Glycopeptides side effects
- chills
- Fever
- Phlebitis
- ototoxicity
- Nephrotoxicity
- Red Man Synd.
What is red man synd?
diffuse flushing as a result of histamine release after RAPID glycopeptides I.V. infusion
Lipopeptides AB example
Daptomycin
Daptomycin spectrum
- similar to vancomycin
- but also active against vancomycin-resistant strains of enterococci and staphylococci
Daptomycin MOA
The drug inserts into the cytoplasmic membrane –> K+ leak –> cell death
Daptomycin pharmacokinetix
Daptomycin is eliminated via the kidney
Daptomycin SE
- Daptomycin may cause myopathy
Creatine phosphokinase should be monitored
Peptide AB example
Bacitracin
Bacitracin MOA
interferes with a late stage in cell wall synthesis in G+’s
Bacitracin administration and SE
- marked nephrotoxicity
- it is limited to topical use (because of the kidney)
What about Mupirocin ?
- it is a natural product from Pseudomonas Fluorescens
- It acts on G+ cocci
- Binds to isoleucyl-tRNA synthetase –> inhibits protein synthesis
Mupirucin Pharmacokinetix and clinical use
- when used topically (it is not absorbed):
- staphylococcal impetigo
- beta-hemolytic streptococci
- Strep. pyogenes
- when used intraNasally:
- eliminate staphylococcal carriage by patients and medical personnel
Mupirucin Toxicity?
- Local itching
- burning sensations
- rash
- erythema
- contact dermatitis.
