Macrobid (Nitrofurantoin) Use in Pregnancy
Nitrofurantoin is safe and recommended as a first-line treatment for urinary tract infections during pregnancy, including the first trimester, with the exception of avoiding use at term (near delivery) due to theoretical risk of neonatal hemolysis. 1, 2
First-Line Treatment Recommendations
Nitrofurantoin is explicitly recommended by multiple international guidelines as first-line therapy for UTI in pregnancy:
- The European Association of Urology (2024) lists nitrofurantoin macrocrystals 50-100 mg four times daily for 5 days or nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days as primary treatment options 1
- Treatment duration should be 4-7 days for asymptomatic bacteriuria or 5-7 days for symptomatic UTI, with 7-14 days recommended for more severe infections 1, 2
- A urine culture must always be obtained before initiating treatment to guide antibiotic selection and confirm diagnosis 2
Safety Profile Across Trimesters
First and Second Trimesters:
- Multiple meta-analyses demonstrate no significant increased risk of major congenital malformations with first-trimester exposure 3, 4
- Cohort studies of 9,275 exposed infants showed no increased risk (RR 1.01,95% CI 0.81-1.26) 4
- A retrospective analysis of 91 pregnancies treated with nitrofurantoin found no drug-related abnormal events, with outcomes comparable to the general U.S. population 5
- Nitrofurantoin has been safely used for over 35 years in pregnancy with a continuing safety record 6
Third Trimester - Important Caveat:
- Nitrofurantoin should be avoided at term (near delivery) due to theoretical risk of hemolytic anemia in neonates with G6PD deficiency 2
- For third-trimester UTIs, cephalexin 500 mg four times daily for 7-14 days is the preferred alternative 2
Critical Clinical Context
Why treatment is essential in pregnancy:
- Untreated bacteriuria increases pyelonephritis risk 20-30 fold (from 1-4% with treatment to 20-35% without treatment) 1, 2
- Treatment reduces premature delivery and low birth weight infants 1, 2
- Pregnancy is the one clinical scenario where even asymptomatic bacteriuria must always be treated 1, 2
- Screening should ideally occur at 12-16 weeks gestation 2
Alternative Agents When Nitrofurantoin Cannot Be Used
If nitrofurantoin is contraindicated or at term:
- Cephalexin (cephalosporins) are excellent alternatives with proven safety profiles 1, 2
- Fosfomycin trometamol 3g single dose is acceptable for uncomplicated lower UTIs 1, 2
- Amoxicillin-clavulanate if pathogen is susceptible 2
Agents to avoid:
- Trimethoprim and trimethoprim-sulfamethoxazole should not be used in the first trimester due to teratogenic effects and are contraindicated in the last trimester 1, 2
- Fluoroquinolones should be avoided throughout pregnancy due to potential cartilage development effects 2
Common Pitfalls to Avoid
- Do not use nitrofurantoin for suspected pyelonephritis, as it does not achieve therapeutic blood concentrations; use cephalosporins or other agents that achieve adequate systemic levels 2
- Do not perform repeated surveillance urine testing or treat asymptomatic bacteriuria multiple times after initial treatment, as this fosters antimicrobial resistance 2
- Do not delay treatment while awaiting culture results in symptomatic patients, as this increases risk of progression to pyelonephritis 2
- Obtain follow-up urine culture 1-2 weeks after completing treatment to confirm cure 2