Glycopeptides Flashcards
Glycopeptides and Short Acting Lipoglycopeptides
Vancomycin
Telavancin
Teicoplanin is a 3rd member but not available in the US
VRE- vancomycin resistant enterococci (especially E. faecium)
A few staph have learned from enterococci
Telavancin was modified from Vanco’s structure
Improved activity against MRSA that is less susceptible to Vanco
Glycopeptides and Short Acting Lipoglycopeptides Spectrum
Bind to terminal D-ala-D-ala chains on peptidoglycan in cell wall, preventing further elongation of peptidoglycan chains
Telavancin has a second mechanism-interferes with the cell membrane, disrupting membrane function
Glycopeptides and Short Acting Lipoglycopeptides Spectrum
Good
MSSA / MRSA
Streptococci
Clostridium difficile
Moderate
Enterococci
Poor
Anything Gram-
Glycopeptides and Short Acting Lipoglycopeptides Adverse Effects
Infusion related reactions
Red man syndrome- histamine mediated reaction; patient may feel warm, flushed, and may develop hypotension; can be prevented by slowing the infusion rate; not a true allergy; antihistamines can ameliorate the reaction; telavancin may also cause reaction (shares same core structure as Vanco)
Ototoxicity
Vanco has historically been considered an ototoxic drug
Evidence linking it with this toxicity is unclear
Renal
Classically associated with nephrotoxicity but historical evidence is poor
Recent studies have shown possible nephrotoxicity in higher doses (such as those commonly used to treat MRSA today)
Early formulation was brown (called Mississippi Mud); current formulation is clear (lacks those possible toxic excipients)
Telavancin has renal toxicity issues as well
Telavancin: in addition to above, taste disturbances and foamy urine can occur
Do not give to pregnant women because of problems seen in animal studies
Glycopeptides and Short Acting Lipoglycopeptides Dosing Issues
Trough concentrations are monitored; different indications have different preferred trough ranges
Higher troughs may be associated with nephrotoxicity
Peak concentrations only used for calculating patient specific PK parameters; do not seem to predict efficacy or safety and should not be drawn for most patients
Glycopeptides and Short Acting Lipoglycopeptides Important Facts
Oral Vanco absorbed poorly
Only used for C. difficile associated disease
IV Vanco does not reach high enough intracolonic concentrations to kill C. diff
Oral achieves sky high gut concentrations so lowest dose is best for majority of patients
If trough is too high, ask if it was drawn correctly; if so, increase dosing interval
Vanco does not kill MSSA as quickly as beta lactams do
Use Cefazolin or Nafcillin instead
MIC creep
Seen with staph and Vanco
Patients receiving Vanco for serious infections caused by staph with an MIC = 2mg/L have worse outcomes than those with lower MICs
Telavancin more rapidly bactericidal than Vanco
Clinical evidence that shows a benefit is lacking
May be useful for patients not responding to other therapies for MRSA
Telavancin is pregnancy category C but should not be used in pregnant women unless absolutely necessary (developmental issues seen in animals)
Good for
Vanco is drug of choice for MRSA and for empiric use when MRSA is a concern (such as nosocomial pneumonia)
Other Gram+ infections when patient has a severe beta lactam allergy
Telavancin indicated for skin and skin structure infections and hospital acquired pneumonia
Long Acting Glycopeptides
Dalbavancin
Oritavancin
Have been designed with PK characteristics that slow their elimination
Each has a half life of over a week; can be doses IV just once for equivalent of 2 weeks of therapy
Only Gram+ coverage
Indicated for skin and skin stricter infections (staph and strep predominate)
Cheaper than hospital admission but one dose could buy a Hawaiian vacation
Long Acting Glycopeptides Spectrum
Good
MSSA / MRSA
Streptococci
Enterococci (Oritavancin)
Moderate
Enterococci (Dalbavancin)
Poor
Anything Gram-
Long Acting Glycopeptides
Adverse Effects
N/V/D and rash
Infusion related reactions can occur with Orit if infused too quickly; given over 3 hours
Orit inhibits warfarin metabolism and may increase risk of bleeding
Long Acting Glycopeptides Important Facts
Prolonged elimination ensures compliance and easy outpatient options
Still need to be monitored for treatment success and adverse effects
Orit interferes with assays for PT- prothrombin time (warfarin) for 24 hours and aPTT- activated partial thromboplastin time (heparin) for 48 hours
Do not use these drugs with Orit during these time frames because monitoring will be unreliable
Dalbavancin has different dosing
Twice: 1000mg on day 1 then 500mg a week later
Once: 1500mg once
Two dose regimen was studied first
Good for
Skin and skin structure infections when Gram+ organisms are involved or highly suspected
