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Nine reasons you should be using less vancomycin



After its discovery in 1953, vancomycin took a while to catch on. Despite its unprecedented activity against Gram positive organisms at the time, early formulations were rife with impurities – forming a brown, turbid solution known colloquially as “Mississippi mud.” With the relatively low rates of Gram positive resistance observed through the 1970s, vancomycin largely remained a drug of last resort. It might have been phased out of the market altogether were it not for the rise of both MRSA and Clostridioides (formerly Clostridium) difficile in the early 1980s.

C. difficile was first linked to antibiotic-associated colitis in 1978. The first large outbreak of community-acquired MRSA infections was reported in Detroit in 1982. As the worldwide incidence of both organisms increased in the following decades, so did rates of vancomycin use. Fortunately, by the 1980s, vancomycin manufacturing had evolved beyond the nephro- and ototoxic sludge used in the 1950s, but a number of other problems with the drug persist to this day. Vancomycin has been a mainstay of antibiotic therapy in US hospitals since the mid-1990s, but here are nine good reasons to move it down your list of preferred antibiotics:

Rates of MRSA infection have been declining in the US over the past 15 years

However you measure it – hospital-acquired, community-acquired, incidence in laboratory cultures or hospital admissions – MRSA has been on the decline for some time now. Only about 5% of the general population and 7% of hospitalized patients are colonized with MRSA, yet we prescribe vancomycin like we expect every patient to have it.

Monitoring is a pain

Vancomycin is one of those rare antibiotics where we can’t just “set it and forget it.” Initial dosing is based mostly on body weight and renal function, but then we give drug levels a few days to equilibrate before checking blood levels to make sure they remain within a narrow therapeutic window. Most hospitals still use the “old” method of dosing, where we try to hit a trough concentration between 15 and 20 mcg/mL. Newer data suggest that it’s better to calculate the area under a 24-hour time-concentration curve (AUC) and maintain a particular ratio to the minimum inhibitory concentration (MIC) of vancomycin against the organism you’re treating. If you’ve ever wondered why your pharmacists are so intent on getting patients off vancomycin, this is largely why.

Dosing is a pain

Vancomycin is usually dosed at least two times a day, with each dose taking no less than 90 minutes to infuse. In the best-case scenario, your patient is tethered to the IV pole for three hours a day. For patients who require more frequent dosing and extended infusion, that figure can go up to nine hours a day.

It ties up IV access

Largely owing to its acidity, vancomycin is not compatible with many other IV medications and usually requires its own dedicated line for administration.

It’s not very well tolerated

Vancomycin induces histamine release, which is what causes the classic “red man syndrome” with diffuse itching and flushing during administration. The best way to avoid RMS is to slow the infusion, but then your patient is tethered to an IV for even longer every day. Vancomycin solution is also fairly caustic, leading to phlebitis with regular administration and significant soft tissue inflammation when infiltration occurs.

It can have pretty severe side effects

Refining the drug may have reduced rates of ototoxicity and nephrotoxicity, but it hasn’t eliminated these risks. Nephrotoxicity seems to be a particular concern when vanco is combined with other potentially nephrotoxic antibiotics like Zosyn. I have had patients require dialysis as a result of vancomycin nephrotoxicity, as well as a few patients who reported permanent hearing loss from exposure to the drug. Furthermore, vancomycin is one of the most common antibiotic causes of DRESS syndrome – a potentially life-threatening hypersensitivity reaction.

It’s comparatively expensive to use

While the drug itself is old and relatively inexpensive, averaging several dollars per gram, monitoring is what drives up the daily cost of vancomycin. You need phlebotomists to draw drug levels, laboratory workers to complete the assays, pharmacists to review the lab results and adjust dosing and pharmacy technicians to mix the revised doses.

It contributes to increases in VRE

If we once thought of MRSA as a terrifying superbug, vancomycin-resistant Enterococcus should worry us even more. VRE treatments are currently limited to a handful of fairly toxic antibiotics, and our efforts to address an overblown risk of MRSA are just setting us up for even greater treatment challenges down the road.

It doesn’t even work that well

In part, this is due to some of the dosing issues above. Considering the risk for toxicity at high levels, we tend to err on the side of underdosing when we’re trying to figure out the right amount of vancomycin for a given patient. Often, this means that we discover on day 3 or 4 that our serum levels have been grossly subtherapeutic, placing patients at risk for inadequately treated infection and potentially contributing to development of vancomycin resistance.

Additionally, vancomycin doesn’t penetrate that well into cerebrospinal fluid, lung tissue or even soft tissue – basically anywhere we need it to go for its most common indications. We see higher rates of treatment failure using vancomycin, rather than beta-lactams, to treat MSSA. Even with MRSA bacteremia, where vancomycin is still considered the preferred treatment agent, an increase in MIC from 1 to 2 mcg/mL – just one dilution – leads to significantly higher rates of treatment failure.

Conclusion

Vancomycin still has its place in current practice – I just don’t think that place should be top of the list for empiric antibiotic choices. If you really need the Gram positive coverage, we have newer agents like daptomycin and linezolid with far fewer drawbacks. In most cases, however, you don’t need to cover that broadly. Do your patients, pharmacists and budgets a favor and think twice before placing that next vancomycin order.

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