Vancomycin-Related Renal Toxicity in Children
Jennifer Le, PharmD
SAN FRANCISCO—Nephrotoxicity from vancomycin therapy develops more quickly in children than adults, according to a study characterizing the renal complications associated with the antibiotic.
The study, described here at the 2009 Interscience Conference on Antimicrobial Agents and Chemotherapy, also showed that higher trough levels of vancomycin, along with other factors, are associated with a greater risk of nephrotoxicity.
“This is the first study [of vancomycin-related nephrotoxicity] that I know of in pediatric patients,” said lead investigator Jennifer Le, PharmD, Assistant Professor of Clinical Pharmacy at the University of California in San Diego. “There are a few studies in adult populations. What we found is somewhat different.”
Data from adult studies suggest that nephrotoxicity tends to develop in patients who have prolonged duration of vancomycin therapy (that is, longer than seven days). In contrast, Dr. Le's team found that the median time to nephrotoxicity in children was four days (range 2-13 days).
She and her colleagues reviewed the medical records of 171 pediatric patients aged 19 years or younger who received 48 hours or more of vancomycin. Of these patients, 24 (14%) had nephrotoxicity and 147 (86%) did not.
The researchers defined nephrotoxicity as an increase in serum creatinine of 0.5 mg/dL or greater or a 50% increase on a least two consecutive days. The two groups were similar with respect to race, gender, and underlying diseases, including renal disease. The mean ages of the patients with and without nephrotoxicity were 7.0 and 6.8 years, respectively.
More patients with nephrotoxicity than those without it stayed in the ICU (92% vs. 53%), received other nephrotoxic agents (58% versus 29%), and experienced shock (50% versus 19%). Nephrotoxicity developed in 14 children even before they had increases in vancomycin troughs.
The mean duration of vancomycin treatment was longer (14 vs. 9 days) and the vancomycin clearances were lower (1.3 vs. 2.4 L/h) in those who experienced nephrotoxicity than those who did not. She noted that the lower drug clearances in patients who developed nephrotoxicity resulted in higher mean trough levels (18 vs. 12 mg/L) but lower vancomycin daily doses (36 vs. 44 mg/kg). Patients with an average vancomycin trough attainment of 15 mg/L or higher had a threefold increased risk of nephrotoxicity than patients with a lower average trough attainment.
“In light of the fact that we have very limited therapeutic options, vancomycin will continue to be used in pediatric populations,” Dr. Le said. “However, I think we need to be very aggressive in the monitoring of the pharmacokinetics [of vancomycin] as well as the renal function,” especially during the early period of drug initiation.