Vancomycin safety concerns

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Concerns about vancomycin | Higher risk of nephrotoxicity with intensive regimens | Risk factors at a glance (Extra detail on specific risk factors) | Therapeutic drug monitoring may reduce risk | Recognition and early intervention | Further information | References


  • Vancomycin guidelines changed in 2009 to recommend higher trough serum concentration targets.1
  • A number of studies have identified a higher risk of nephrotoxicity when these higher trough concentrations are achieved2-8 however, there are limited data to suggest a direct causal relationship between nephrotoxicity and a specific vancomycin concentration.1,8
  • There are several other risk factors for developing vancomycin-induced nephrotoxicity, including older age, obesity, severe illness and having compromised renal function.9,10
  • Monitoring of trough serum vancomycin concentrations to reduce the risk of nephrotoxicity is recommended for people at high risk.1

Concerns about vancomycin – past and present

Vancomycin was initially dubbed ’Mississippi mud‘ because of the brown colour of early formulations that were only about 70% pure. The impurities in these formulations are thought to have contributed to the incidence of adverse reactions.11,12 With improved manufacturing in the 1960s, purity increased to 75% and up to 95% by 1985. Concurrently, reporting of serious adverse events associated with vancomycin were reduced.1

Last year, the US FDA tested six vancomycin products in response to concerns about quality issues associated with their use.13 While testing revealed no evidence of quality issues, it prompted discussion in the infectious disease community (the ‘Emerging Infections Network’) about vancomycin and acute kidney toxicity .14 One member argued the purity of generic vancomycin contributes to an increase in cases of vancomycin-induced nephrotoxicity , another member attributed the rise to new recommendations for maintaining higher trough serum levels of vancomycin.14

‘“… We almost never saw toxicity with levels 5–10 [mg/L], or even 10–15 [mg/L]. As soon as we instituted 15–20 [mg/L] for serious infections, we saw renal toxicity.”14
Anonymous member, Emerging Infections Network

Studies controlling for other factors that may have contributed to nephrotoxicity report the incidence of vancomycin-induced nephrotoxicity to be 5% to 7%.1,15 While this is a low incidence of a usually reversible condition, it has become a real concern with increased uptake of the recommended intensive dosing.16 In addition, use of vancomycin has increased in hospitals and ICUs in Australia by around 9% and 13% respectively over the past five years.17

Higher risk of nephrotoxicity with intensive vancomycin regimens

In their consensus statement in 2009 the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) recommended maintaining trough vancomycin levels at > 10 mg/L to avoid the development of bacterial resistance. Serum vancomycin concentrations of 15–20 mg/L are recommended for complicated infections.1 In Australia, the recommended target trough concentrations are 15 ± 3 mg/L (i.e. 12 to 18 mg/L).18

Many studies have demonstrated that elevated vancomycin trough levels (>15 mg/L) predict development of nephrotoxicity in patients with other known causes of acute kidney injury , with an overall incidence of 27% for trough exposure of 15–20 mg/L.2-8 A 2009 study identified vancomycin trough levels as the pharmacodynamic index that best describes the relationship between exposure and toxicity (Figure 1).2

vancomycin concentration and probability of nephrotoxicity

Figure 1. Probability of nephrotoxicity with various initial vancomycin trough concentrations2
From: Lodise TP, et al. Clin Infect Dis 2009;49(4):507–14, by permission of the Infectious Diseases Society of America.

The temporal relationship between elevated vancomycin trough concentrations and development of nephrotoxicity is unclear in most studies, leaving some uncertainty about the cause–effect relationship.8

Further studies are required to ensure the safety of higher vancomycin trough concentrations over a prolonged period.1


Risk factors at a glance

  • Unmonitored and prolonged use of vancomycin1,19
  • Being elderly9
  • Receiving vasopressor therapy in ICU20 (see Extra detail - below)
  • Severe illness (classified by a high Acute Physiology and Chronic Health Evaluation (APACHE) II score)5,20
  • People with sepsis3,20
  • Weight ≥101 kg2,6 (see Extra detail - below)
  • Patients with compromised renal function (see Extra detail - below)

Extra detail on specific risk factors

Vasopressor therapy

In a 2009 study it was observed that patients in ICU have a higher baseline risk for development of nephrotoxicity than patients not in ICU at a lower trough concentration threshold.2,20 This increased risk is most likely secondary to these patients having a poorer health status and an increased number of comorbidities.

High body weight (≥101 kg)

There are limited data on dosing in obese patients; however, initial dosages should be based on actual body weight and adjusted based on serum vancomycin concentrations to achieve therapeutic levels.2,6

Compromised renal function

Even a modest decline in glomerular filtration rate (GFR) from >60 mL/min to 45 to 59 mL/min can lead to a 2-fold increase in risk of developing an acute kidney injury.15 Patients with chronic kidney disease (CKD) are more likely to have higher serum concentrations of vancomycin and thus have increased risk of developing vancomycin-induced nephrotoxicity.15 Use of other nephrotoxic agents is associated with an increased incidence of nephrotoxicity1 i.e. concomitant use of aminoglycosides with vancomycin has been associated with an increased incidence of nephrotoxicity up to 35%.15

Use therapeutic drug monitoring in patients receiving vancomycin1

Therapeutic drug monitoring may reduce risk of vancomycin-induced nephrotoxicity and underdosing


As pharmacodynamic markers (e.g. INR for warfarin) are not available to assess the effect of vancomycin, therapeutic drug monitoring is recommended to avoid underdosing and serious toxicity.1,21 While the evidence does not support monitoring peak serum vancomycin concentrations, monitoring of trough concentrations is recommended in people:1,18

  • receiving doses targeted to produce sustained trough drug concentrations of 15–20 mg/L
  • receiving concurrent nephrotoxic agents (e.g. aminoglycosides or loop diuretics)
  • receiving prolonged courses of therapy (i.e. more than 3 to 5 days)
  • with unstable kidney function.

The practice of routine monitoring and adjusting of serum vancomycin concentrations has been debated for many years. The controversy has resulted from conflicting evidence regarding the best use of serum vancomycin concentrations; either using it to predict and prevent drug-induced toxicity or as a measure of efficacy in treating infections.1

Recognition and early intervention

While treatment with vancomycin for severe infections occurs in hospitals, GPs can help reduce the risk of vancomycin-induced nephrotoxicity by encouraging their patients to have an up-to-date medicines list.22,23

At the first sign of kidney dysfunction, review the patient's medicines list to identify medicines that are renally cleared or nephrotoxic. If multiple renally cleared/nephrotoxic medicines are present and the patient is clinically stable, the most recently added medicines should be stopped.23

Further information

For further information about vancomycin and nephrotoxicity see the Australian Therapeutic Good Administration's Medicines Safety Update, Volume 4, Number 4, August 2013.

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  2. Lodise TP, Patel N, Lomaestro BM, et al. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis 2009;49:50714. [PubMed]
  3. Hermsen ED, Hanson M, Sankaranarayanan J, et al. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf 2010;9:914. [PubMed]
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  11. Elting LS, Rubenstein EB, Kurtin D, et al. Mississippi mud in the 1990s: risks and outcomes of vancomycin-associated toxicity in general oncology practice. Cancer 1998;83:2597607. [PubMed]
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