Anti-infectives. (Drugs, Pregnancy, and Lactation).

I frequently get calls from physicians who have questions about the safety of different anti-infectives during pregnancy or breast-feeding. In this and future columns, I will review what is known about this large class of drugs when used in these two situations.

* Penicillins. There is no evidence that exposure to penicillins during any stage of pregnancy is associated with birth defects or direct fetal toxicity. All are rated pregnancy category B and cross the placenta throughout pregnancy. Products that combine a penicillin with a [beta]-lactamase inhibitor, such as clavulanate with amoxicillin (Augmentin) or ticarcillin (Timentin) and sulbactam with ampicillin (Unasyn), also appear to be safe during pregnancy.

When used near term, however, indirect toxicity may occur with extended-spectrum penicilins. Ampicillin has been linked to an increased risk of ampicillin-resistant Escherichia coli sepsis in newborns, so many centers no longer use it for pregnant women who carry group B streptococci. Instead, they use the more narrow-spectrum penicillin G.

A recent study found an increased incidence of necrotizing enterocolitis in newborns exposed to amoxicillin/clavulanate in utero, attributed to antibiotic-induced abnormal colonization of the neonatal intestinal tract with Clostridium difficile. However, further study is needed to confirm this association.

All penicillins are excreted into breast milk but are compatible with breastfeeding. Nursing infants exposed to these agents should be observed for possible adverse effects such as diarrhea, thrush, and allergic reactions.

* Cephalosporins. Cephalosporins, rated category B, are believed to cross the placenta and are excreted into breast milk. There is no evidence of indirect or direct toxicities to the embryo, fetus, or newborn exposed to any cephalosporin, or of any problems reported with exposure through breast milk. Cephalosporins are compatible with nursing, but the infant should be monitored for adverse effects similar to those caused by the penicillins.

* Tetracyclines. All are rated D. They are not teratogenic or embryo-fetotoxic in the first trimester. But starting in the second trimester, they are rapidly taken up by mineralizing tissue such as the teeth or bone, causing discoloration of the deciduous teeth. This process also inhibits fetal skeletal growth but is clinically insignificant because skeletal growth undergoes a catch-up phase when ...