What is the first‑line oral antibiotic for an uncomplicated urinary‑tract infection in a pregnant woman, and what alternatives are recommended if nitrofurantoin is contraindicated?

First-Line Antibiotic for Uncomplicated UTI in Pregnancy

Nitrofurantoin 100 mg orally twice daily for 5–7 days is the preferred first-line treatment for uncomplicated urinary tract infections in pregnant women, except during the final weeks of pregnancy. 1

Recommended First-Line Agents

• Nitrofurantoin remains the primary choice due to its excellent safety profile in pregnancy, high efficacy against E. coli (the most common uropathogen), and minimal resistance development despite over 60 years of clinical use. 1, 2

• The standard regimen is nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5–7 days, achieving clinical cure rates of 88–93% and bacteriological cure rates of 81–92%. 1

• Nitrofurantoin has been used safely for decades to treat acute uncomplicated UTIs, recurrent infections, and asymptomatic bacteriuria of pregnancy, with a continuing excellent safety record. 3

Alternative First-Line Options When Nitrofurantoin Is Contraindicated

Fosfomycin Trometamol

• Fosfomycin 3 g as a single oral dose is an appropriate alternative, offering the advantage of single-dose therapy with comparable safety in pregnancy. 1, 4

• Meta-analysis shows no significant difference in clinical cure rates (RR 0.95% CI 0.81–1.12) or microbiological cure rates (RR 0.96,95% CI 0.84–1.08) between fosfomycin and nitrofurantoin within 4 weeks of treatment. 4

• Fosfomycin is classified as an "Access" antibiotic by the WHO, reflecting its favorable resistance profile and safety. 1

Third-Generation Cephalosporins

• Cefixime and other third-generation oral cephalosporins are rational alternatives due to high sensitivity of E. coli, good efficacy, and established safety in pregnancy. 2

• Cephalosporins should be used for 5–7 days when nitrofurantoin cannot be used. 1

Trimethoprim-Sulfamethoxazole (with important restrictions)

• TMP-SMX 160/800 mg twice daily for 3 days may be considered only if local E. coli resistance rates are < 20% and the patient has not received this agent in the preceding 3 months. 1, 5

• TMP-SMX should be avoided in the first trimester due to theoretical risk of neural tube defects and near term due to risk of neonatal hyperbilirubinemia. 1

Critical Contraindications and Timing Considerations for Nitrofurantoin

• Avoid nitrofurantoin in the final 2–4 weeks of pregnancy (near term) due to theoretical risk of hemolytic anemia in the newborn. 5

• Do not use nitrofurantoin if pyelonephritis is suspected (fever > 38°C, flank pain, costovertebral angle tenderness, nausea/vomiting) because it does not achieve adequate renal tissue concentrations. 1, 5

• Nitrofurantoin is contraindicated when creatinine clearance is < 30 mL/min due to reduced efficacy and increased risk of peripheral neuropathy. 1

Antibiotics to Avoid in Pregnancy

• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for pyelonephritis or complicated infections only, not for uncomplicated cystitis, due to FDA safety warnings and rising resistance rates. 1, 5

• Amoxicillin or ampicillin alone should never be used empirically due to globally high resistance rates among uropathogens. 5

Clinical Decision Algorithm

1. Confirm uncomplicated lower UTI: dysuria, frequency, urgency, suprapubic discomfort without fever, flank pain, or systemic symptoms. 1

2. Assess gestational age:

   • First trimester through mid-third trimester: Nitrofurantoin 100 mg twice daily for 5–7 days. 1, 2
   • Final 2–4 weeks of pregnancy: Use fosfomycin 3 g single dose or cefixime instead. 1, 2

3. If nitrofurantoin is contraindicated (renal impairment, near-term pregnancy, or suspected upper tract involvement):

   • Use fosfomycin 3 g single dose, or
   • Use cefixime or another third-generation cephalosporin for 5–7 days. 1, 2

4. If upper tract infection is suspected (pyelonephritis): Switch to a fluoroquinolone or third-generation cephalosporin with adequate tissue penetration; hospitalization may be required. 1, 5

Common Pitfalls to Avoid

• Do not prescribe nitrofurantoin for "borderline" upper-tract symptoms; any fever or flank pain warrants a different agent with better tissue penetration. 1, 5

• Do not use TMP-SMX empirically without knowing local resistance rates; treatment failure rates are unacceptably high when resistance exceeds 20%. 1, 5

• Do not treat asymptomatic bacteriuria in pregnancy without antibiotics—this is one exception where treatment is indicated to prevent pyelonephritis and adverse pregnancy outcomes. 5

• Do not obtain routine post-treatment urine cultures in asymptomatic patients; cultures are only needed if symptoms persist or recur within 2 weeks. 1, 5