In utero and in vitro exposure to beta-lactams impair kidney development in the rat

beta-Lactam antibiotics are widely used because of their lack of toxicity i n humans. However, during pregnancy, exposure of the fetus is likely to occ ur because beta-lactam antibiotics cross the placenta. The potential advers e effects of two penicillins (ampicillin, amoxicillin) and of one cephalosp orin (ceftriaxone) were examined in rat kidney development. Two experimenta l approaches were used: metanephros organ cultures to analyze the direct ef fect of the drug and maternal treatment to assess the consequences of in ut ero exposure. For in vitro experiments, metanephroi were removed from 14-d- old fetuses and grown with or without the antibiotic at a concentration ran ging from 10 to 1000 mu g/ml for 6 d. For in vivo experiments, pregnant rat s were treated with penicillin at 100 mg/kg per d for 5 d, a period overlap ping early renal organogenesis. Both penicillins alter renal development in vitro in a dose-dependent manner, from a dose of 10 mu g/ml for ampicillin and 100 mu g/ml for amoxicillin. In young animals exposed to penicillins i n utero, a mild oligonephronia was present and cystic tubule dilation was o bserved in newborn and in young animals as well. Ceftriaxone weakly impairs in vitro nephrogenesis except at the dose of 1000 mu g/ml that blocks kidn ey development completely. No effect on nephron ontogeny was observed follo wing in utero exposure, but an interstitial inflammation was present in the medulla of 2-wk-old rats. In conclusion, these data show that beta-lactams , at therapeutic doses, are harmful to fetal rat kidneys.