The use of intravenous colistin among children in the United States: results from a multicenter, case series

Abstract

Background: A rapid increase in multidrug-resistant Gram-negative infections has led to a reemergence of colistin use globally. Although it is well described among adults, colistin use and its associated toxicities in children are poorly understood. We report findings from the largest case series of pediatric colistin use to date.

Methods: We queried pediatric infectious diseases specialists from the Emerging Infections Network to identify members who had prescribed intravenous colistin within the past 7 years. We collected relevant demographic and clinical data. Bivariate analyses and multivariable logistic regression were performed.

Results: Two hundred twenty-nine pediatric infectious diseases specialists completed the survey (84% response); 22% had prescribed colistin to children. Among respondents, 92 cases of colistin use from 25 institutions were submitted. The most commonly targeted organisms were multidrug-resistant Pseudomonas (67.4%), multidrug-resistant Acinetobacter -baumanii (11.9%), carbapenemase-producing Enterobacteriaceae (13.0%) and extended-spectrum β-lactamase producing Enterobacteriaceae (5.4%). Development of resistance to colistin was observed in 20.5% of patients. Additional antimicrobial therapy was administered to 84% of patients, and 22% of children experienced nephrotoxicity (not associated with dosage or interval of colistin prescribed). Renal function returned to baseline in all patients. Children aged ≥13 years had approximately 7 times the odds of developing nephrotoxicity than younger children, even after controlling for receipt of additional nephrotoxic agents (odds ratio 7.16; 95% confidence interval: 1.51-14.06; P = 0.013). Four children exhibited reversible neurotoxicity.

Conclusions: Most pediatric infectious diseases specialists have no experience prescribing colistin. Colistin use in children has been associated primarily with nephrotoxicity and, to a lesser extent, neurotoxicity, both of which are reversible. Emergence of resistance to colistin is concerning.

FIGURE 1

Number of children prescribed intravenous colistin from 2005 to 2011 in the United States based on response to survey of pediatric infectious diseases physicians with P value representing trend over time.