Metabolic tolerance to arginine: Implications for the safe use of arginine salt-aztreonam combination in the neonatal period

Two similar cohorts of low birth weight infants whose size was appropriate for gestational age randomly received either aztreonam-arginine plus ampicillin (n=15) or gentamicin plus ampicillin (n=15) for empiric treatment of neonatal sepsis. The regimens were infused together with glucose at >5 mg/kg per minute, and immediate (4 hours) and cumulative (3 days) effects were assessed. Serum arginine and insulin values rose immediately after administration of aztreonam (containing 0.15 mmol of arginine per kilogram), but there were no changes in the gentamicin-treated cohort; no differences occurred in either cohort in serum concentrations of glucose, ammonia, potassium, creatinine, and bilirubin. After 3 days of antibiotic therapy (n=13), the baseline serum arginine concentration was almost twice as high in the aztreonam group and showed a similar further rise and fall during the 4 hours after infusion; arginine urinary fractional excretion (normalized to creatinine clearance) decreased in the gentamicin group. The indirect bilirubin concentration rose more (p<0.001) in the aztreonam-treated infants (5.1 to 11.5 mg/dl (87 to 196 μmol/L)) than in the gentamicin-treated infants (5.5 to 8.1 mg/dl (94 to 138 μmol/L)). Thus a modest differential bilirubin response and modestly elevated baseline serum arginine level occurred after the 3-day low-arginine doses of this study; serum ammonia and glucose concentrations were not affected. Aztreonam-arginine in neonates was well tolerated metabolically, and we believe that it can be used safely in conjunction with attention to glucose and bilirubin metabolism.