Vancomycin, properly dosed, is as safe on the kidneys as linezolid

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Consider multiple factors in treatment of gram-positive infections

Multiple factors must be considered in determining the optimal antibiotic treatment of gram-positive infections including but not limited to clinical and microbiological efficacy, development of resistant microorganisms, adverse effects, and costs. Several recent meta-analyses have reported conflicting results regarding whether linezolid is superior to vancomycin in clinical and/or microbiological efficacy, but all have reported increased nephrotoxicity with vancomycin (PLoS ONE 2013;8:e58240; Int. J. Antimicrob. Agents 2013;41:426-33; Eur. J. Clin. Microbiol. Infect. Dis. 2013).

However, none of these performed metaregression analyses to determine whether there is an association between vancomycin troughs and risk of nephrotoxicity. While the study by Dr. Davies et al. suggests such a relationship, there is inadequate data to determine if the higher vancomycin troughs, which were associated with creatinine elevations above 1.0 mg/dL, were necessary to eradicate the Gram-positive infections. Furthermore, despite the adjustment for severity of illness, there may have been a selection bias in the initial choice of antibiotics. Lastly, treatment selection for Gram-positive infections should also take into account: the costs and resources necessary to monitor vancomycin troughs, and the feasibility of performing timely and appropriate dose adjustments based on troughs to achieve a therapeutic yet nontoxic level.

Lillian S. Kao, MD, FACS, of the department of surgery, University of Texas Health Science Center at Houston.



LAS VEGAS – Vancomycin is as safe on the kidneys of critically ill patients as linezolid, so long as trough levels don’t exceed the recommended upper limit of 20 mcg/mL, according to researchers from the University of Virginia in Charlottesville.

"When correct dosing is performed, the use of alternative agents to treat Gram-positive infections – specifically to avoid [vancomycin] nephrotoxicity – is unnecessary. Vancomycin use in critically ill patients is no different than linezolid use regarding nephrotoxicity or new-onset need for hemodialysis," said lead investigator Stephen Davies, a resident in the department of surgery, said at the annual meeting of the Surgical Infection Society.

Dr. Stephen Davies

The kidney safety of vancomycin has been in doubt, with mixed results from prior studies. To shed light on the issue, Dr. Davies and his team compared renal outcomes in 298 critically ill patients treated with vancomycin for 571 Gram-positive infections with outcomes in 247 patients treated with linezolid for 475 Gram-positive infections.

Infection sites included the lungs, peritoneum, blood stream, and urinary tract, among others, and isolates included Staphylococcus aureus (77 methicillin-resistant S. aureus), Enterococcus faecium (67 vancomycin-resistant Enterococcus), E. faecalis, and Streptococcus species. Vancomycin patients were dosed at 15-20 mg/kg, with serial trough monitoring, and treated for a mean of 16.2 days, vs. 14.3 days for linezolid. Patients were on no other nephrotoxic agents.

In the end, "there were no [statistically significant] differences between the two groups regarding maximum creatinine during treatment, final creatinine after treatment, change in creatinine maximum and initial values, and final and initial creatinine values." There were also no differences "in new-onset hemodialysis or death," Dr. Davies said.

APACHE II (Acute Physiology and Chronic Health Evaluation II) scores above 30 and initial creatinine levels above 1.2 mg/dL both predicted the need for new-onset hemodialysis, but antibiotic choice did not.

Those same two variables also predicted an increase in creatinine of more than 1.0 mg/dl during treatment; vancomycin use did, as well (relative risk, vancomycin 0.49; 95% confidence interval: 0.25-0.94). Concerned, the team looked into the issue. "What we found was that a rise in creatinine was typically not encountered until trough levels greater than 20 mg/dL were reached. As long as you stay within the recommended doses, you should be safe," Dr. Davies said.

There were no statistically significant baseline differences between the two groups in renal function, hemodialysis, creatinine levels, or APACHE II scores.

Despite the results, Dr. Philip Barie, who helped moderate Dr. Davies’ talk, said in an interview that he’s still concerned about vancomycin kidney safety.

"We are having to use higher doses to treat tougher bugs, and whereas nephrotoxicity pretty much went away with vancomycin after they purified the drug [decades ago], now we are having to use higher doses more, and nephrotoxicity is beginning to creep back into the picture. You have to dose really carefully, and if you have an organism that is among the more resistant to vancomycin, the safest thing to do with vancomycin is to use linezolid," said Dr. Barie, a professor of surgery and public heath at Cornell University, New York.

Dr. Davies and Dr. Barie reported no relevant disclosures.

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