Effects of two antibiotics on hepatic function in low birth weight infants : ampicillin vs. cefotaxime

In 21 low birth weight infants with two regimens of antibiotic therapy during the first 3 days of life possible hepatotoxic side effects were studied 8 days after the last administration of the tested drugs. Fourteen of the infants were treated with ampicillin/gentamicin and 7 received cefotaxime/gentamicin. The serum concentrations of total bile acids, the activities of transaminases in serum and the cumulative 15N excretion in urine after administration of 3 mg of 15N-labeled methacetin/kg of body weight were used as markers of hepatotoxic side effects. Neither the concentrations of total bile acids (22.6 +/- 12.1 and 19.4 +/- 10.8 mM, respectively) nor the activities of transaminases (alanine aminotransferase, 0.27 +/- 0.06 vs. 0.30 +/- 0.09 mumol/second/liter; aspartate aminotransferase, 0.46 +/- 0.11 vs. 0.49 +/- 0.10 mumol/second/liter) were different between the two groups. In contrast the cumulative 15N excretion in urine was significantly lower in the group treated with cefotaxime/gentamicin than in the group treated with ampicillin/gentamicin (17.2 +/- 6.4 vs. 33.0 +/- 5.1% of intake; P less than 0.01) and also lower than the reported age-related reference values. On the 28th day of life no differences could be found between the cumulative 15N excretion in the urine of the infants treated with cefotaxime/gentamicin and the reported age-related reference values of this test. The results indicate a limited capacity of the monooxygenase system of the liver of low birth weight infants during the first weeks of life and a specific reversible influence of cefotaxime on this hepatocellular system. Further investigations are required to evaluate the clinical relevance of this drug-specific inhibition of the hepatic monooxygenase pathway.