Is Macrobid (nitrofurantoin) safe to use during pregnancy for a woman with a urinary tract infection (UTI)?

Macrobid (Nitrofurantoin) in Pregnancy

Nitrofurantoin is safe and recommended as first-line treatment for UTIs during the first and second trimesters of pregnancy, but should be avoided near term (late third trimester/at delivery) due to theoretical risk of neonatal hemolytic anemia in G6PD-deficient newborns. 1

Recommended Dosing and Duration

• Nitrofurantoin macrocrystals 50-100 mg four times daily for 5 days OR nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days are the primary treatment options for UTIs in pregnancy 1
• Treatment duration should be 4-7 days for asymptomatic bacteriuria or symptomatic UTI, with 7-14 days reserved for more severe infections 1
• Always obtain a urine culture before initiating treatment to guide antibiotic selection and confirm diagnosis 1, 2

Trimester-Specific Guidance

First and Second Trimesters

• Nitrofurantoin is the preferred first-line agent with excellent safety data 1, 2
• Meta-analysis of cohort studies (9,275 exposed infants) showed no increased risk of major malformations (RR 1.01,95% CI 0.81-1.26) 3
• Historical data spanning over 35 years demonstrates consistent safety and efficacy 4
• ACOG states that prescribing nitrofurantoin in the first trimester is appropriate when indicated, as untreated infections pose greater risks to mother and fetus 5

Third Trimester (Near Term)

• Avoid nitrofurantoin at term/near delivery due to theoretical risk of hemolytic anemia in G6PD-deficient neonates 1
• Switch to cephalexin 500 mg four times daily for 7-14 days as the preferred alternative for late third trimester UTIs 1, 2

Alternative Antibiotics When Nitrofurantoin Cannot Be Used

• Cephalexin (cephalosporins) - excellent safety profile, achieves adequate blood and urinary concentrations 1, 2
• Fosfomycin trometamol 3g single dose - acceptable for uncomplicated lower UTIs 1, 2
• Amoxicillin-clavulanate - appropriate if pathogen is susceptible 1, 2
• AVOID trimethoprim/trimethoprim-sulfamethoxazole in first trimester (teratogenic effects) and contraindicated in last trimester 1, 2
• AVOID fluoroquinolones throughout pregnancy due to potential cartilage development effects 1, 2

Critical Clinical Context: Why Treatment Cannot Be Delayed

• Untreated bacteriuria increases pyelonephritis risk 20-30 fold (from 1-4% with treatment to 20-35% without) 1, 2
• Treatment reduces premature delivery and low birth weight 1, 2
• Pregnancy is the ONE clinical scenario where even asymptomatic bacteriuria must always be treated due to significant progression risk 1, 2
• Implementation of screening programs decreased pyelonephritis rates from 1.8-2.1% to 0.5-0.6% 2

Common Pitfalls to Avoid

• Do NOT use nitrofurantoin for suspected pyelonephritis - it does not achieve therapeutic blood concentrations; use cephalosporins or other agents with adequate systemic levels 1, 2
• Do NOT delay treatment while awaiting culture results in symptomatic patients - this increases risk of progression to pyelonephritis 1
• Do NOT withhold appropriate antibiotics in first trimester - untreated infections pose far greater risks than the medications 5
• Obtain follow-up urine culture 1-2 weeks after completing treatment to confirm cure 1, 2
• Do NOT perform repeated surveillance testing or treat asymptomatic bacteriuria multiple times after initial screen-and-treat, as this fosters antimicrobial resistance 2

Addressing Mixed Evidence

While three case-control studies suggested a slight increased risk (OR 1.22,95% CI 1.02-1.45) for major malformations, the more reliable cohort study data showed no increased risk 3. The case-control studies are more prone to recall bias and confounding. ACOG, European Association of Urology, and multiple international guidelines continue to recommend nitrofurantoin as first-line therapy based on decades of clinical experience and the preponderance of evidence showing safety 1, 2, 5.