Which antibiotic is safest to treat a first trimester urinary tract infection?

Clinical guidelines recommend screening and treating bacteriuria in early pregnancy, since untreated urinary tract infections (UTIs) can have serious maternal and neonatal consequences. However, evidence is limited and inconsistent regarding the risk of congenital malformations following antibiotic exposure during early pregnancy.To examine this issue, researchers at the Washington University School of Medicine compared the risk of congenital malformations following first-trimester exposure to various antibiotic agents used to treat UTI. The population-based cohort study included commercially insured pregnant individuals aged 15–49 years who were treated for UTI during the first trimester of pregnancy from 2006–2022, and their live-born infants. Study subjects were required to have a first-trimester prescription for an oral antibiotic agent commonly used to treat UTIs, dispensed by an outpatient pharmacy. The antibiotics studied were nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) and beta-lactams. Beta-lactams (cephalosporins and penicillins) served as the reference group because these agents are considered safe during pregnancy. Congenital malformations were identified using validated algorithms based on diagnosis codes up to 365 days after birth. Regression models were used to estimate propensity score–weighted risk ratios (RRs) and risk differences.Results showed the following:The cohort included 71,604 eligible first-trimester pregnancies (median maternal age, 30 years).Of these, 42,402 (59.2%) were exposed to nitrofurantoin, 3,494 (4.9%) to TMP-SMX, 3,663 (5.1%) to fluoroquinolones and 22,045 (30.8%) to beta-lactams.Gestational age differed by antibiotic (nitrofurantoin, 62 [45–77] days; TMP-SMX, 26 [13–59] days; fluoroquinolones, 18 [9–27] days; β-lactams, 63 [48–77] days).The absolute risk of any malformation per 1,000 infants was 19.8 (95%CI, 18.0–21.8) for β-lactams, 21.2 (95%CI, 19.9–22.7) for nitrofurantoin, 23.5 (95%CI, 18.8–28.9) for fluoroquinolones, and 26.9 (95%CI, 21.8–32.8) for TMP-SMX.After accounting for confounding, the risk of any congenital malformation was higher for TMP-SMX (RR, 1.35; 95%CI, 1.04–1.75), but similar for nitrofurantoin (RR, 1.12; 95%CI, 1.00–1.26) and fluoroquinolones (RR, 1.18; 95%CI, 0.87–1.60), compared with beta-lactams.TMP-SMX was associated with increased risk of severe cardiac malformations (RR, 2.09; 95%CI, 1.09–3.99), other cardiac malformations (RR, 1.52; 95%CI, 1.02–2.25), and cleft lip and palate (RR, 3.23; 95%CI, 1.44–7.22) compared with beta-lactams.Risk of other malformation types did not differ by agent, although some estimates were imprecise. Results were generally consistent across sensitivity analyses.The authors conclude that in this cohort study of first-trimester antibiotic exposure, the risk of any malformation, severe cardiac malformation, other cardiac malformation and cleft lip/palate was higher for infants exposed to TMP-SMX compared with beta-lactam antibiotics. The increased risk of any congenital malformation associated with first-trimester exposure to TMP-SMX translated to one additional malformation per 145 pregnant individuals treated with TMP-SMX vs beta-lactams. No elevated risk was observed for nitrofurantoin or fluoroquinolones. ReferencesOsmundson SS, Nickel KB, Shortreed SM, et al. First-trimester antibiotic use for urinary tract infection and risk of congenital malformations. JAMA Network Open 2025;8(7):e2519544. (accessed July 15, 2025).

Which antibiotic is safest to treat a first trimester urinary tract infection?

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