Jim Kling

September 24, 2013

DENVER — Switching patients at high risk for kidney injury from vancomycin to other drugs does not prevent nephrotoxicity, a new study suggests.

Previous research has linked nephrotoxicity to vancomycin, and some studies have shown that alternative drugs are associated with lower rates.

"There have not been that many agents to treat infections due to Staphylococcus aureus, especially methicillin-resistant ones. But recently, there have been a lot of approved drugs with indications similar to vancomycin," said study author Joseph Carreno, PharmD, assistant professor of pharmacy practice at the Albany College of Pharmacy and Health Sciences in New York.

"These agents are now more readily available and commonly used. Physicians sometimes want to avoid vancomycin in patients who are perceived as being at high risk for acute kidney injury; however, that strategy has never formally been evaluated," he told Medscape Medical News.

Dr. Carreno presented the study results here at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.

Recently, there have been a lot of approved drugs with indications similar to vancomycin.

His team conducted a prospective randomized controlled trial of subjects 18 years or older who had at least 2 risk factors for nephrotoxicity. Participants were receiving dose-optimized vancomycin for bacterial healthcare-associated pneumonia, osteomyelitis, septic arthritis, endocarditis, bacteremia, or acute bacterial skin and skin-structure infections.

Patients either continued to receive vancomycin or were switched to an alternative therapy, such as ceftaroline, daptomycin, or linezolid.

Study outcomes included inpatient mortality, 30-day mortality, nephrotoxicity as defined in vancomycin guidelines, and the Acute Kidney Injury Network (AKIN) definition of nephrotoxicity, which has been modified to reflect the clinical significance of relatively small rises in serum creatinine.

"We did not see a difference in the instance of acute kidney injury with the 2 definitions of nephrotoxicity — the traditional definition used in the literature and the vancomycin guidelines, and the alternative definition from the AKIN — so we did not see a benefit from switching to alternative agents," said Dr. Carreno.

Table. Nephrotoxicity and Mortality Outcomes

Outcome Alternative Therapy, % (n = 49) Vancomycin, % (n = 51) P Value
Inpatient mortality 6.3 2.0 .36
30-day mortality 12.2 4.5 .26
Nephrotoxicity 6.3 9.8 .65
AKIN nephrotoxicity 31.3 31.4 .99


"These newer agents are our reserve treatments for complicated infections, so we should use them when they're appropriate," Dr. Carreno explained.

"I'm a proponent of using them when there is strong evidence for their use, but I would not recommend using those agents solely to prevent acute kidney injury without another indication."

There were several posters at the meeting on vancomycin-associated nephrotoxicity. "We're hearing more and more about nephrotoxicity associated with vancomycin," said Anurag Malani, MD, medical director for infection prevention and antimicrobial stewardship at St. Joseph Mercy Hospital in Ann Arbor, Michigan, who attended the session.

"There's also been concern about increasing resistance," Dr. Malani pointed out. "This study is intriguing. It is an issue we face every day in the hospital: Should we switch someone to an alternative to vancomycin when their creatinine is going up or when they already come in with renal dysfunction?"

This is a single-center study with a relatively small number of patients. "At least from this group's experience, we can say that there really is no reduction in acute kidney injury in patients who receive alternatives to vancomycin. I think that's important, but we have to keep in mind the limitations of the study," Dr. Malani told Medscape Medical News.

Dr. Carreno and Dr. Malani have disclosed no relevant financial relationships.

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract K-711. Presented September 11, 2013.


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