Vancomycin 1g for Everyone, Right?

From our very own ED pharmacist, Natalija Farrell:

Vanco

The Issue

  • Methicillin-resistant Staphylococcus aureus (MRSA) infections and MRSA-related hospitalizations continue to increase.1
  • Vancomycin remains the cornerstone for the treatment of suspected or confirmed MRSA infections.
  • Its efficacy is measured by troughs (goal 10-20 mg/L) and troughs <10 mg/L foster vancomycin resistance.2
  • Due to the increased mortality in patients with vancomycin susceptible aureus with higher minimum inhibitory concentrations (“MIC creep”) and emergence of vancomycin intermediate or resistant S. aureus (VISA, VRSA),3-5 it is even more paramount to dose vancomycin correctly and target troughs 15-20 mg/L.
  • Emergency Departments are underdosing vancomycin in >70% of patients (especially in obese patients).
    • Most patients received vancomycin 1 g IV. 6-7

 Vancomycin Dosing2,8-10

  • Traditional Dosing: Vancomycin 15 – 20 mg/kg IV
  • Loading Doses: Vancomycin 25 – 30 mg/kg IV x1
    • Should be used to in critically ill patients (e.g. sepsis, febrile neutropenia, meningitis, endocarditis, etc.)
    • More rapidly achieve therapeutic levels
    • Minimizes vancomycin resistance
    • Not associated with increased adverse effects
  • Renal function determines the frequency not the dose
    • Totally daily doses >4 g increase the risk of nephrotoxicity
Weight* Traditional Vancomycin IV Dosing Vancomycin IV Loading Dose
50 kg 750 mg, 1 g 1.25 g, 1.5 g
60 kg 1 g, 1.25 g 1.5 g, 1.75 g
70 kg 1 g, 1.25 g, 1.5 g 1.75 g, 2 g
80 kg 1.25 g, 1.5 g 2 g
90 kg 1.5 g, 1.75 g 2 g
100 kg 1.5 g, 1.75 g, 2 g 2 g
110 kg 1.75 g, 2 g 2 g
>110 kg 2 g 2 g
*Actual body weight

Dose rounded to the nearest 250 mg to a maximum of 2 g

Summary

  • Proper vancomycin dosing will help curb the increasing incidence VISA and VRSA
  • Vancomycin 1 g IV is not appropriate for all patients.
  • Critically ill patients should receive vancomycin loading doses (e.g. 50 kg = 1.5 g, 60 kg = 1.75 g; ≥70 kg = 2 g)

References

  • Mera RM, Suaya JA, Amrine-Madsen H, et al. Increasing role of Staphylococcus aureus and community-acquired methicillin-resistant Staphylococcus aureus infections in the United States: a 10-year trend of replacement and expansion. Microb Drug Resist 2011;17(2):321-8.
  • Rybak MJ, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists.Am J Health Syst Pharm 2009;66(1):82-98.
  • van Hal SJ, et al. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis.Clin Infect Dis2012;54(6):755-71
  • Lodise TP, et al. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin.Antimicrob Agents Chemother 2008;52(9):3315-20.
  • Appelbaum PC. The emergence of vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. Clin Microbiol Infect 2006;12(S1):16-23.
  • Rosini JM, et al. Prescribing habits of vancomycin in the emergency department: are we dosing appropriately?J Emerg Med 2013;44(5):979-84
  • Fuller BM, et al. Emergency department vancomycin use: dosing practices and associated outcomes.J Emerg Med 2013;44(5):910-8.
  • Reardon J, Lau TTY, and Ensom MHH. Vancomycin loading doses: a systematic review. Ann Pharmacother 2015;49(5):557-65.
  • Rosini JM, Laughner J, Levine BJ, Papas MA, Reinhardt JF, and Jasani NB. A randomized trial of loading vancomycin in the emergency department. Ann Pharmacother 2015;49(1):6-13.
  • Lodise TP, Lomaestro B, Graves J, Drusano GL. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother 2008;52:1330-6.

 

5 thoughts on “Vancomycin 1g for Everyone, Right?

    • I think this is an interesting study, but I would not recommend using Bactrim IV in place of vancomycin. The vancomycin dosing (1g IV Q12H) in this study may not have been adequate for many patients. While there was no statistical difference in treatment failure overall (38% vs 27%) and for bacteremia (56% vs 40%), Bactrim failures were almost 1.5x higher than vancomycin. Mortality overall was low (~10%), but Bactrim’s 30 day mortality rate in bacteremic patients was double that of vancomycin (34% vs 18%, nonsignificant). The IDSA guidelines don’t include Bactrim in their bacteremia or pneumonia treatment guidelines. Vancomycin, linezolid ($$$, weak MAOI inhibitor), and daptomycin ($$$, takes ~45 minutes to reconstitute, not for pneumonia) are the recommended MRSA treatment options per our antibiogram.

      Some other things to think about with Bactrim IV- It requires a lot of volume (Each 80mg of trimethoprim requires 75 mL of D5W –> 320mg trimethoprim requires at least D5W 600mL). It’s only compatible with D5W. Bactrim IV contains a high concentration of propylene glycol, which can exacerbate hypotension. Bactrim is a combination drug with each component having a different amount (IV: TMP 16 mg/ml and SMX 80 mg/mL; DS tab TMP 160 mg and SMX 800 mg). The different concentrations and not knowing that Bactrim is dosed by according to the trimethoprim (TMP) can lead to lead to preparation errors. Bactrim IV is not stocked in the Omnicells.

  1. I have also heard that Vanc+Zosyn dosed together increases the nephrotoxic risk associated with each individual medicine, any thoughts or data to support this? Should we change our clinical practice?

    • There are a few retrospective studies in different patient populations (internal medicine and ICU) that suggest vancomycin + Zosyn increases the risk of AKI. Prospective studies are need to confirm the association. It’s also important to remember that our one time doses of vancomycin + Zosyn are highly unlikely to cause a kidney injury. While the above studies haven’t effected my current practice, they do serve as a reminder to select more narrow antibiotic(s) with when appropriate.

      For most infections requiring broad spectrum antibiotics, vancomycin + cefepime is an appropriate alternative to vancomycin + Zosyn. You could argue that Zosyn is “more broad” due to its anaerobic cover, which cefepime doesn’t offer. In patients requiring broad spectrum antibioitics who don’t need anaerobic coverage, vancomycin + cefepime would be the more narrow choice in this example.

      References:
      1) Gomes DM, et al. Comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or cefepime. Pharmacotherapy. 2014;34:662-669.
      2)Burgess LD, Drew RH. Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam. Pharmacotherapy. 2014;34:670-676.
      3) Moenster RP, et al. Acute renal failure associated with vancomycin and beta-lactams for the treatment of osteomyelitis in diabetics: piperacillin-tazobactam as compared with cefepime. Clin Microbiol Infect. 2014;20:O384-O389.

  2. Thank you for this! I definitely learned something new. I’ve been guilty of the 1 gram knee jerk dosing, and this will change my practice. Looking forward to more ED Pharm posts.

Leave a Reply