Question - Ceftriaxone is a third-generation cephalosporin with broad spectrum activity against both Gram-negative and Gram-positive bacteria. What potential toxicities have limited the use of this drug in neonatal patients?
Answer - One recent review on this topic noted “We included nine studies regarding ceftriaxone side effects, primarily spontaneous reports, published case reports, and small case series. Reports of bilirubin displacement attributed to ceftriaxone included increases in serum bilirubin necessitating antibiotic change in a subset of infants after administration of ceftriaxone. One study described self-resolving biliary sludge after ceftriaxone administration in six of 80 infants. Cardiopulmonary adverse events included a report of eight cardiopulmonary events related to concomitant ceftriaxone-calcium infusion, including seven infant deaths. Additional cardiopulmonary events reported included perinatal asphyxia, pulmonary hypertension, and thrombocytosis. However, the available literature had small sample sizes, poor external validity, and inconsistent outcome ascertainment methods, which made it impossible to estimate the magnitude of risk.” These authors concluded “Concomitant administration of intravenous ceftriaxone and calcium-containing solutions should be avoided in neonates. However, further controlled studies are needed to assess whether bilirubin displacement associated with the use of ceftriaxone is clinically relevant, particularly in healthy term and near-term neonates with mild hyperbilirubinemia.” (Donnelly PC et al. Ceftriaxone associated biliary and cardiopulmonary adverse events in neonates: A systematic review of the literature. 2017 Paediatric Drugs 19(1): 21-34)