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Effects of two antibiotics on hepatic function in low birth weight infants: ampicillin vs. cefotaxime
G Boehm1, H Senger, F B Spencker
1Department of Pediatrics, University of Leipzig, Germany.
Insights
Antibiotic therapy in low birth weight infants was studied for liver side effects. Cefotaxime/gentamicin showed a reversible impact on the liver
Area of Science:
- Neonatal pharmacology
- Hepatotoxicity assessment
- Drug metabolism in infants
Background:
- Low birth weight infants often require antibiotic therapy.
- Assessing potential drug-induced liver injury (hepatotoxicity) is crucial in this vulnerable population.
- Understanding drug effects on the developing liver monooxygenase system is essential.
Purpose of the Study:
- To investigate potential hepatotoxic side effects of two antibiotic regimens in low birth weight infants.
- To compare the effects of ampicillin/gentamicin versus cefotaxime/gentamicin on liver function.
- To evaluate the influence of these antibiotics on the hepatic monooxygenase system.
Main Methods:
- Studied 21 low birth weight infants receiving either ampicillin/gentamicin or cefotaxime/gentamicin.
- Measured serum total bile acids and transaminase activities as markers of liver injury.
- Assessed hepatic function using 15N-methacetin clearance, a marker of monooxygenase activity.
Main Results:
- No significant differences in bile acids or transaminases between the two antibiotic groups.
- 15N-methacetin excretion was significantly lower in the cefotaxime/gentamicin group compared to ampicillin/gentamicin.
- This reduced excretion normalized by the 28th day of life, suggesting a reversible effect.
Conclusions:
- The liver monooxygenase system in low birth weight infants has limited capacity in early life.
- Cefotaxime, in combination with gentamicin, demonstrated a specific, reversible inhibitory effect on this hepatocellular system.
- Further research is needed to determine the clinical significance of this drug-induced inhibition.
Abstract:
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.