Reversible Nephrotoxicity and Neurotoxicity with Colistin Use Among Children

SAN DIEGO, CA— Pranita Tamma, MD, MHS, from The Johns Hopkins Medical Institution, Baltimore, MD, reported that colistin use in children has been associated primarily with nephrotoxicity and to a lesser extent, neurotoxicity, at IDWeek 2012.

A rapid increase in multidrug resistant (MDR) Gram-negative infections has occurred, prompting a reemergence of colistin use around the world. However, colistin use and its associated toxicities in the pediatric population are not as well described as they are in adults. Dr. Tamma and colleagues queried pediatric specialists from the Emerging Infections Network to identify members who had prescribed intravenous (IV) colistin within the past seven years. Data on patient demographics and targeted organism, occurrence of toxicity, and recent foreign travel were all collected and analyzed.

A total of 92 unique cases of colistin use were submitted and the median age of children was 16 years.  Children with or without cystic fibrosis were compared, as respective cases would require different sites of infections and dosing intervals. Children without cystic fibrosis were administered colistin 2.5mg/kg every 12 hours; children with cystic fibrosis were administered 2.5mg/kg every 8 hours.

The most commonly targeted organisms were MDR Pseudomonas (67%), MDR Acinetobacter baumanii (15%), carbapenamase-producing Enterobacteriaceae (13%), and extended-spectrum β-lacatamase producing Enterobacteriaceae (5%). Development of resistance to colistin on therapy was observed in 20.5% of patients; additional antimicrobial combination therapy (e.g., carbapenems, aminoglycosides) was administered to 84% of patients.

Further analyses revealed that 22% of children experienced nephrotoxicity, but this was not associated with dose or interval of colistin prescribed; renal function did return to baseline in all patients upon discontinuation of agent. Children >12 years old had approximately seven times the odds of developing nephrotoxicity than younger children, even after controlling for receipt of additional nephrotoxic agents (P=0.013). In addition, four children exhibited reversible neurotoxicity (two parasthesia cases; two severe headache cases).

“Emergence of resistance to colistin is concerning,” stated Dr. Tamma. Her team was able to conclude that colistin use in children has been associated with non-dose limiting nephrotoxicity (20%), and neurotoxicity (4%), both of which were reversible.