Tuesday, May 29, 2018

The plague that is vancomycin troughs

How important are vancomycin levels? Not very.... at least as a marker of efficacy. True, higher levels probably are associated with increased nephrotoxicity (above 15 mcg/mL) - Antimicrob Agents Chemother. 2013 ;57:734-44
But the notion that troughs of 15-20 mcg/mL are the holy grail of therapeutic drug monitoring targets is simply not supported by data.
What we know: vancomycin AUC/MIC in the mid 300 to 400s (let's just say > 400) or so range is likely the best PK/PD parameter that predicts therapeutic success (pic 1).
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 Much of these data come from the early 2000's when typical vancomycin MICs were less than 1 (Clin Infect Dis. 2007;15;44:1536-42 - pic 2). 
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It turns out that when the MIC is 1 (generally most common these days), the probability of achieving an AUC/MIC of 400 is pretty much equally poor whether the trough is 10-15 or 15-20 (pic 3) but if it is 0.5 or less, the PTA (probability of target attainment is essentially 100% regardless of trough.
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the problem with using troughs to predict efficacy is assuming that they're a good surrogate for AUC (which is kind of reason we use troughs since AUC is more difficult to measure). In reality they are not (pic 4).
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How about some clinical data? Pic 5 (Clin Infect Dis. 2012 Mar 1;54:621-9.) is results from the 2012 vancomycin vs linezolid nosocomial PNA trial: ignore the superiority of linezolid for clinical success and note that the success rate for vancomycin based on day 3 troughs (0-7.9: 48%, 8-12.3: 46%, 12.4-17.4: 45.5%, > 17.4: 45.5%), shocking? Shouldn't be considering the vast majority of MICs was 1 mcg/mL.
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What about post-hoc data from the ATTAIN trial with telavancin vs vancomycin? (pic 6), no difference in cure rate regardless of troughs but more nephrotoxicity with higher troughs.
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Take home point? patient receiving vancomycin for "severe" MRSA PNA and improving, trough comes back at 13 mcg/mL, why increase the dose?

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