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).
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).
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.
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).
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.
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.
Take home point? patient receiving vancomycin for “severe” MRSA PNA and improving, trough comes back at 13 mcg/mL, why increase the dose?