All Things Vancomycin

Believe it or not, vancomycin was first isolated in the fifties from an isolate of dirt in the jungles of Borneo by a missionary. It is a naturally occurring antibiotic made by the soil bacterium Actinobacteria. The name vancomycin comes from the word vanquish.  Initially it was used as a sort-of last resort for penicillinase-producing strains of Staphylococcus aureus.  Today, vancomycin is one of the most widely used antibiotics for the treatment of serious gram positive infections involving methicillin-resistant S. aureus (MRSA). Years ago, early use of vancomycin was associated with several different types of toxicities including infusion related effects (Red Man Syndrome), nephrotoxicity (kidney), and possible ototoxicity (damage to ears).  It was determined later that the majority of these adverse effects were due to the early formulations that contained impurities; however, by that time, its use was decreased with the development of other penicillin-type medicines like methicillin, oxacillin, and nafcillin).  Thanks to MRSA, Vancomycin is making a huge comeback, or has been since the early 1980s.

On a side note, Red Man Syndrome is not an allergic reaction.  This can be managed with a histamine blocker or slowing down the infusion.  Can't tell you how many times I have seen this listed as an allergy to vancomycin on someone's profile.

In monitoring Vancomycin, trough serum concentrations are the most accurate method.  Typically draw the trough level prior to the fourth dose (steady-state).  Keep trough levels above at least 10 mg/L to avoid development of resistance.  For a pathogen with an MIC of 1 mg/L, the minimum trough concentration would have to be at least 15 mg/L.  For complicated infections, the optimal trough concentrations are 15-20 mg/L to improve penetration, increase optimal serum concentrations, and improve clinical outcomes.

How to dose?  Dosing vancomycin is a bit of an art, but start at 15-20 mg/kg using actual body weight.  Many hospitals encourage a maximum dose of 2 grams.  Definitely adjust dose in renal dysfunction.

 

Creatinine Clearance(based on Cockcroft and Gault and not eGRF) Dose*
>60 ml/min Uncomplicated Infections: 10-15 mg/kg q12h1 

Serious Infections: Consider loading dose of 25mg/kg IV x1, followed by 15-20 mg/kg q8-12h (45-60mg/kg/day divided q12h or q8h)2

 

40-60 ml/min 10-15 mg/kg q12h-q24h
20-40 ml/min 5-10 mg/kg q24h
10-20 ml/min 5-10 mg/kg q24h-q48h
<10 ml/min

10 - 15 mg/kg IV loading dose x1; redose according to serum levels

Hemodialysis 15-20 mg/kg load, then 500 mg IV post HD only
CVVH 10-15 mg/kg q24h

* round dose to 250mg, 500mg, 750mg, 1g, 1.25g, 1.5g, 1.75g or 2g (maximum: 2gm/dose)

Higher total daily doses of vancomycin have been associated with nephrotoxicity

1 For patients with uncomplicated infections requiring vancomycin, trough levels of 10-15 mcg/ml are recommended.

2 For patients with serious infections due to MRSA (central nervous system infections, endocarditis, ventilator-associated pneumonia, bacteremia or osteomyelitis) , trough levels of 15-20 mcg/ml are recommended.

Vancomycin troughs are not recommended in patients in whom anticipated duration of therapy is short (≤ 3 days)

Trough levels are recommended for routine monitoring (for intermittent hemodialysis, a pre-dialysis level should be drawn). Trough levels should be obtained within 30 minutes before 4th dose of a new regimen or dosage change.

Once weekly monitoring is reasonable in patients with stable renal function and clinical status. (Data supporting safety or prolonged troughs of 15-20 mcg/ml is limited.)

There is a great app out there I recommend called Vancomycin ClinCalc Full.  The author also has a website called ClinCalc you can check out to see if the dosing matches how your particular program wants you to do it.

I don't earn a dime for that link either, I just enjoy finding quality programs to work more efficiently.

I love Dr. Walter Crittenden, PharmD MD "An Infections Disease Compendium:  A Persiflagers Guide" on the iPad as well.

One of my biggest pet-peeves is when I hear someone say, "Oh I have blown their kidneys!" in regards to one serum creatinine level coming back higher.  Hey, let's wait until 2-3 consecutive high serum creatinine concentrations (increase of 0.5 mg/dL or 150% increase from baseline, whichever is greater) after several days before making such a claim.  Seriously.

And the "Rants and Screeds" of Dr. Crittenden, "Vancomycin is a shitty drug; mostly static, toxic, lousy pharmacokinetics, penetrates poorly into all tissues.  When compared to beta lactams, it is always worse."

Gotta love that!

Don't Be Afraid to Fail

BCPS 2012 Results: Blonde Pharmacist will repeat!