Treating UTIs in reproductive-age women—Proceed with caution
A new study suggesting that nitrofurantoin and sulfonamides are teratogenic highlights the need for a risk-benefit analysis when your patient is a woman of reproductive age.
WHAT'S NEW: A large-scale study provides evidence of risk
Previous case studies and meta-analysis have shown no link between the use of nitrofurantoin and congenital abnormalities.8 Similarly, sulfonamides have not appeared to pose significant teratogenic risk. This is the first large-scale study evaluating the risk of birth defects associated with antibiotic use during pregnancy, and therefore provides evidence of risk not previously available.
CAVEATS: Study design raises questions of recall bias
The retrospective case-control methodology used in this study leaves open the possibility of recall bias, misclassification bias, and confounding bias. The length of time from actual exposure to data collection could affect the accuracy of participants’ memories. The data gathered were not cross-verified against medical records, and other issues, such as the possible effect of medications for other infections (eg, antivirals and antifungals), could not be measured. However, women who did not know or were unsure of their medication exposure history were excluded from the analysis, which should reduce the risk of this potential bias.
The investigators also controlled for several important sources of potential confounding bias, and the reporting rates were similar among participants in both the case and control groups. These measures provide some assurance that the outcomes are valid.
It would be unethical (and extraordinarily expensive) to conduct a prospective randomized controlled trial to confirm these findings. Case-control methodology is the most practical way to assess for the risk of birth defects, and our literature review suggests that this is the most rigorous study to date. In our view, the potential harm from continuing to use these antibiotics for pregnant women and women who may become pregnant far outweighs the risk that these findings may be erroneous.
That said, a final caveat is the fact that even a several-fold increase in the risk of a rare major birth defect such as those reported in this study is still a rare risk. There may be clinical situations in which the benefits of using nitrofurantoin or sulfonamides in women who are or may become pregnant outweigh the potential risks.
CHALLENGES TO IMPLEMENTATION: Finding an alternative treatment
The main challenge to implementing this new recommendation lies in choosing alternative antibiotics with which to treat UTIs in reproductive-age women and bacteriuria in pregnancy. Obtaining a pregnancy test in sexually active patients of reproductive age who are not using a reliable form of contraception seems like a prudent first step.
If the pregnancy test is positive, cephalexin should be a good initial choice until the results of culture and sensitivities are available. In the event of Enterococcus infection (for which cephalosporins are not active) or other organisms resistant to cephalosporins, the sensitivity results should provide guidance.3
Acknowledgment
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources; the grant was a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
