This is the third installment in a series of columns on anti-infective drugs. * Sulfonamides. This class is rated C during most of pregnancy and D near term. Sulfonamides readily cross the placenta throughout pregnancy, and significant drug levels may persist in newborns for several days after birth. Even though they aren't teratogenic, they can cause toxic effects in the newborn, including jaundice, hemolytic anemia, and----theoretically----kernicterus. These risks are greatest for premature infants, so a sulfonamide should not be used in premature labor. Sulfonamides can be taken during breast-feeding, but should be avoided in women whose babies are jaundiced or have glucose-6-phosphate dehydrogenase (G6PD) deficiency, or are ill, stressed, or premature.
* Aztreonam (Azactam). There is no evidence that this [beta]-lactam, rated B, is teratogenic or embryo-fetotoxic in animals. But there are no reports in human pregnancy, so I recommend avoiding it in the first trimester until such data are available. Because of low concentrations in breast milk, exposure is probably not a risk to the nursing infant.
* Carbapenems. The combination agent imipenem-cilastatin (Primaxin), rated C, is not teratogenic in animals but was embryocidal and lethal in pregnant monkeys at about three times the recommended human dose. Human reports indicate that it is safe during the second half of gestation; these data are limited, and there are no first-trimester reports. I'd be cautious about using it early in gestation until we know more. There are no reports of use during lactation; only small amounts are found in breast milk so it is probably safe.
Meropenem (Merrem), rated B, is considered safe during the second half of gestation, because there's no. evidence of fetal harm in rats and monkeys. Still, there are no reports of meropenem use in humans during pregnancy or lactation. If a pregnant or nursing woman really needs this agent, and there is no alternative, the benefit probably outweighs the risk.
* Metronidazole (Flagyl). This agent is rated B because studies in mice and rats have found no evidence of fetal harm. But it is mutagenic in bacteria and carcinogenic in rodents, which has raised concern about use during pregnancy. To date, however, these effects have not been demonstrated in human studies.
The many studies of this drug during human pregnancy include two metaanalyses and two population-based studies. These four studies found no association with birth defects. There is also no evidence of mutagenic or car-cinogenic effects in humans, but more study on the potential for inducing cancer is needed. Cautious use during breast-feeding is therefore advised.
* Spectinomycin (Trobicin). This drug, given as a single intramuscular dose, is rated B and approved for use during pregnancy for gonococcal infections in women allergic to cephalosporins. However, there are no human or animal data, so the safest course is to avoid this drug during the first trimester. It is poorly absorbed, so use during lactation is not a concern.
* Nitrofurantoin (Macrodantin). This drug, rated B, is commonly used in pregnancy for treatment and prophylaxis of urinary tract infections. There is no evidence of toxicity or teratogenicity in mice or rats at doses dose to those used in humans, although there has been a low incidence of birth defects and growth retardation in mice exposed to higher doses. Fetal lung papillary adenomas have been seen in mice offspring exposed to 19 times the human dose, but this has not been seen in humans.
No association with congenital defects has been reported in a large body of data in human pregnancies. However, hemolytic anemia is a potential complication in people who are G6PD deficient and in neonates because of immature erythrocyte enzyme systems (glutathione instability), so pregnant women should avoid this drug during delivery.
Although breast milk levels of nitrofurantoin are about sixfold that of maternal plasma levels, it is considered compatible with breast-feeding. Hemolytic anemia is a potential complication in breast-fed babies with G6PD deficiency.
* Trimethoprim. The wisest course at this time is to avoid trimethoprim in the first trimester because of recent reports of congenital malformations (oral clefts, spinal anomalies, and urinary tract and cardiovascular defects) following exposure in the first trimester when used alone or in combination with another drug. Trimethoprim, a folate antagonist, is teratogenic and embryotoxic in rats and rabbits and readily crosses the human placenta. It is rated C, but I believe it should be rated D during the first trimester. It is considered compatible with breast-feeding.
GERALD G. BRIGGS is pharmacist clinical specialist, Women's Hospital, Long Beach Memorial Medical Center; clinical professor of pharmacy, University of California, San Francisco; and adjunct associate professor of pharmacy University of Southern California, Los Angeles.
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