Chemical structure of vancomycin — you knew that, right?
I took care of a patient many years ago with MRSA. The severity of the infection required a prolonged treatment course, and vancomycin was the default option. Cripes, it was the only option. He ultimately was discharged on home IV therapy, and as usual we had a plan to monitor his renal function and vancomycin levels weekly.
The twist was that his wife was a nephrologist. Weekly blood tests weren’t enough; she wanted twice-weekly labs. She scrutinized all the results with meticulous intensity, plotting them on a spreadsheet so we could stop the drug “at the first hint of trouble.”
When we spoke, I was strictly instructed to dose the drug so that the trough concentrations never exceeded 10 mcg/mL. “Vancomycin is poison,” she said. A memorable quote!
(The patient did fine, low troughs notwithstanding. It was a team effort! And yes, I changed some details for patient confidentiality.)
Fast forward to today, with our target vancomycin troughs between 15–20 — or with area under the curve monitoring — and there’s no doubt that some of this nephrologist’s heightened concerns about nephrotoxicity have come to pass. Any doubts that vancomycin has nephrotoxicity have been dispelled by study after study showing a clear dose relationship between drug exposure and renal injury. It’s particularly problematic in older patients or those with other risk factors for renal disease.
The problems with vancomycin are much on my mind, as a trio of great first-year ID fellows just reviewed a particularly difficult outpatient vancomycin case. They cited one study of 130 patients on outpatient vancomycin where a whopping 28% developed some sort of renal injury. Risk factors were higher cumulative dose, a longer duration of therapy, underlying kidney disease, and use of other nephrotoxic meds. No surprise, there are a lot of studies with similar findings.
Of course, when I was treating my patient way back when, options for MRSA treatment were highly limited. What’s changed today is that we now have several alternatives to vancomycin — alternatives that are better in many important ways. As a result, it’s time we demote vancomycin substantially when discharging patients who need ongoing antibiotic therapy.
Here’s why:
- Other options are less toxic. Daptomycin, linezolid, ceftaroline, trimethoprim-sulfamethoxazole, and doxycycline aren’t perfect; all drugs have side effects, after all. But in OPAT land, vancomycin troubles greatly exceed issues caused by these other antimicrobials. For the comparison between vancomycin and daptomycin, our astute ID fellows identified two typical studies (one from 2014, the other 2018) showing significantly fewer adverse events for daptomycin. Bottom line — it’s safer!
- Monitoring vancomycin levels is hugely resource intensive. Area under the curve monitoring, now the preferred method for people with stable renal function, requires the input of a pharmacist, and isn’t available in many settings. Targeting the optimal trough concentrations, especially in people with changing renal function, is an obstacle course that could lead to an awful lot of falls, sometimes with no safety net. It’s never quite right!
- What’s a “trough,” anyway? If you haven’t had a “trough” vancomycin level checked at the wrong time — the error disclosed to you by your observant patient, their caretaker, or your home care service — you haven’t yet experienced the deep frustrations of monitoring home IV vancomycin. On some extreme misfires, a peak level is drawn accidentally, scaring everyone, but providing essentially useless data that needs to be repeated as a “true trough.” Fun times.
- Oral therapy can be substituted for intravenous in a high proportion of patients. Cue Dr. Brad Spellberg here for his very convincing, “Busting 75 Years of ID Myth” talk!
- Who’s paying for all this careful monitoring? As I’ve written before, home IV therapy is the classic hot potato clinical service, terribly reimbursed, and vancomycin is definitely the most common culprit in adding to this burden. For us physicians, the measures of our productivity still predominantly come from face-to-face patient visits and procedures — not calling skilled nursing facilities to chase down creatinine results and vancomycin levels.
- Prolonged infusion times make patients prisoners of vancomycin administration. Each dose takes more than an hour — sometimes much longer. This is true for all home vancomycin recipients, but the ones I truly feel bad for are those who require every 8-hour vancomycin dosing — they are spending what must feel like most of their waking hours watching IV vancomycin slowly infuse. With its once-daily dosing and an administration time lasting just a few minutes, it’s no wonder patient satisfaction is significantly higher with daptomycin than vancomycin. I bet they’d be even higher with dalbavancin or oritivancin prior to discharge, though unfortunately the clinical research on using these drugs for severe MRSA infections is limited.
- There’s no longer a cost advantage. Daptomycin and linezolid prices have (at last) dropped substantially from their stratospheric peaks in their brand-name days. Trimethoprim sulfamethoxazole and doxycycline are even less expensive. Additionally, alternatives to vancomycin spare the additional costs of drug level monitoring and drug toxicity.
Conspicuously absent from the above list are citations about treatment effectiveness. If we knew that vancomycin had superior efficacy to alternatives for home IV therapy, then one could justify all the hassle. But if such studies exist, I’m certainly not familiar with them.
So prior to discharging that patient on home vancomycin, think very carefully about safer and more convenient alternatives. There is almost always going to be a better option.