Mark Johnson, Pharm.D., BCPS
Associate Professor and Director of
Postgraduate Education
Vancomycin—A glycopeptide
• Mechanism of action
– Inhibits cell wall synthesis by binding to the D-Ala-D-Ala
terminus of of peptidoglycan pentapeptide, which as a
result inhibits transglycosylase, preventing peptidoglycan
elongation and cross-linking
• Mechanism of Resistance: modification of D-Ala-DAla binding site (D-Ala is replaced by D-lactate), and
thus vancomycin cannot bind to its target site
• Spectrum of Activity
– Gram + organisms only (Staph and Strep); particularly
Staphylococci (MRSA), penicillin-resistant Streptococcus
– Synergistic in vitro with gentamicin and streptomycin
against Enterococcus faecium and Enterococcus faecalis
– Increased incidence of VRE, but otherwise good coverage
against enterococcus
– Vancomycin Resistance: VISA (GISA), VRSA
– Kills Staph slowly compared to beta-lactams
– Bacteriocidal
• Clinical Use
– PO for C. difficile colitis
– IV for everything else (usually serious infections including
bacteremia, endocarditis, meningitis)
– Also an alternative for PCN allergic patients
• Pharmacokinetics
– Poorly absorbed from GI tract
– Widely distributed with Vd 0.4-1L/kg; CSF levels 730% of serum levels with meningeal inflammation;
lung tissue 5-41% of serum levels
– Þ-distribution phase 30min; ß-elimination half-life
– 90% excreted by glomerular filtration
• Adverse Effects:
– Nephrotoxicity (uncommon, but ? Increasing incidence)
and Ototoxicity (rare--possibly related to very high trough
• More common with older preparation (“Mississippi
• Toxicity may be increased with other nephro/oto-toxic
• Adverse Effects:
– “Red man” or “red neck” syndrome
• Infusion-related flushing reaction caused by release of
• Prevented by increasing the infusion time
– Phlebitis
– Rash
– Chills
– Fever
• Dosing
– 15-20mg/kg (as actual body weight) every 812h for most patients with normal renal
function when MIC < 1
– Dose modify interval depending on renal
– In seriously ill, LD 25-30mg/kg can be used to
facilitate rapid attainment of target trough
– Goal AUC:MIC >400 overall; not achievable if
MIC > 2 with conventional dosing
AJHP 2009;66:82-98
• Monitoring:
– Troughs most accurate and practical for
monitoring efficacy
– Trough historically 5-10mcg/ml, now
>10mcg/mL because of MIC creep
– Complicated infections (endocarditis,
osteomyelitis, meningitis, HAP caused by
Staph aureus): trough 15-20mg/L
– Scr periodically
AJHP 2009;66:82-98
• Dosage Forms:
– Capsules (Vancocin®) 125mg and 250mg
– Injection
• Premixed: 500mg (100ml); 1g (200ml)
• Powder for reconstitution: 500mg, 1gm, 5gm, 10gm
Telavancin (Vibativ™)
• Lipoglycopeptide antibiotic (synthetic
derivative of vancomycin) for the treatment of
complicated gram-positive skin infections
• MOA: inhibits bacterial cell wall synthesis
and disrupts bacterial cell membrane function
Televancin vs. Vancomycin
Telavancin (Vibativ™)
• Antimicrobial Activity:
– Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus
pneumoniae (incl. penicillin resistant), Streptococcus angiosus group
– Enterococcus faecalis
– Not VRE, not VRSA, maybe GISA
– PAE of up to 6 hours
• Efficacy:
– Skin and Skin Structure: comparable to
vancomycin and anti-staphylococcal penicillins
– HAP: comparable to vancomycin
Telavancin (Vibativ™)
• ADR’s:
– >10%: taste disturbance, n&v, foamy urine
– Renal dysfunction: 3% (vs. 1% vancomycin) (monitor renal
function before/during therapy)
– Possible: QTc prolongation, Red-man syndrome
– Pregnancy C: reduced fetal weights, digit/limb deformities in
animals (need to do pregnancy test)
• Drug Interactions:
– Is a CYP3A4 inhibitor, so potential exists
– Can interfere with PT, INR, aPTT, ACT, factor Xa as binds to
artificial phospholipid surface—collect samples when telavancin
is at trough
Telavancin (Vibativ™)
• Dosing:
– 10mg/kg Q24h IV over 60min
CrCl 30-50ml/min: 7.5mg/kg Q24h
CrCl 10-29ml/min: 10mg/kg Q48h
CrCl < 10ml/min: insufficient data
Severe hepatic impairment: unknown
– No level monitoring
• Cost:
– 750mg vial: $150
– 250mg vial: $50

similar documents