What antibiotic(s) are recommended for treating an uncomplicated urinary tract infection in a pregnant woman before 34–36 weeks gestation without glucose‑6‑phosphate dehydrogenase deficiency?

Antibiotic Treatment for Uncomplicated UTI in Pregnancy

Nitrofurantoin, fosfomycin, or a short course of beta-lactams (amoxicillin-clavulanate or cephalosporins) are the recommended first-line antibiotics for treating uncomplicated urinary tract infections in pregnant women before 34–36 weeks gestation without G6PD deficiency. 1, 2, 3, 4

First-Line Antibiotic Options

Nitrofurantoin (Preferred)

• Nitrofurantoin 100 mg orally twice daily for 5–7 days is safe and effective throughout pregnancy until 34–36 weeks gestation, when it should be avoided due to theoretical risk of neonatal hemolytic anemia. 1, 2, 3, 4
• This agent achieves excellent urinary concentrations against E. coli (the causative organism in 75–95% of pregnancy-related UTIs) with minimal resistance rates worldwide. 1, 4
• Nitrofurantoin preserves intestinal microbiota better than broad-spectrum agents, reducing collateral antimicrobial damage. 1

Fosfomycin (Excellent Single-Dose Alternative)

• Fosfomycin trometamol 3 g as a single oral dose provides 24–48 hours of therapeutic urinary concentrations and is considered safe throughout all trimesters of pregnancy. 1, 2, 3, 4
• Clinical cure rates approach 91% with this convenient single-dose regimen, improving adherence compared to multi-day courses. 1
• Multiple international guidelines and a large multicenter study (5,362 pregnancies) confirm fosfomycin's safety profile, showing no significant differences in gestational age, neonatal weight, Apgar scores, or pregnancy complications compared to untreated controls. 5, 3

Beta-Lactam Antibiotics (When First-Line Agents Unsuitable)

• Amoxicillin-clavulanate 500/125 mg orally twice daily for 3–7 days or third-generation cephalosporins (e.g., cefixime) for 3–7 days are acceptable alternatives when nitrofurantoin or fosfomycin cannot be used. 2, 3, 4
• Beta-lactams show somewhat inferior efficacy (approximately 89% clinical cure, 82% microbiological eradication) compared to nitrofurantoin or fosfomycin but remain safe throughout pregnancy. 1, 4
• Cefixime demonstrates high sensitivity against E. coli, good safety profile, and excellent compliance in pregnant women. 2

Treatment Duration and Monitoring

• 4–7 days of therapy is recommended for most agents (except fosfomycin, which is a single dose); single-dose regimens other than fosfomycin show higher rates of bacteriuria persistence and are not recommended. 6
• A 7-day course of nitrofurantoin was more effective than single-dose therapy in preventing low birth weight (RR 1.65,95% CI 1.06–2.57) in a large multicenter trial of 714 pregnant women. 6
• Obtain urine culture before initiating antibiotics and adjust therapy based on susceptibility results to ensure targeted treatment. 7, 4

Critical Contraindications and Timing Restrictions

• Avoid nitrofurantoin after 34–36 weeks gestation due to theoretical risk of neonatal hemolytic anemia in the immediate peripartum period. 1, 3
• Avoid trimethoprim-sulfamethoxazole (TMP-SMX) in the first trimester (neural tube defect risk) and near term (kernicterus risk); it should only be used in the second trimester when the organism is proven susceptible and other options are unavailable. 1, 3, 4
• Fluoroquinolones are contraindicated throughout pregnancy due to concerns about cartilage and skeletal development in the fetus. 3, 4
• Aminoglycosides should be avoided except in severe pyelonephritis requiring hospitalization, due to ototoxicity and nephrotoxicity risks. 4

Rationale for Treating All Bacteriuria in Pregnancy

• Untreated asymptomatic bacteriuria progresses to acute pyelonephritis in up to 40% of pregnant women, which carries significant maternal and fetal risks including preterm labor, low birth weight, and increased neonatal mortality. 6, 8, 4
• Antimicrobial treatment of asymptomatic bacteriuria in pregnancy probably reduces the risk of pyelonephritis (moderate-quality evidence) and may reduce the risk of low birth weight and preterm labor. 6
• All bacteriuria detected during pregnancy should be treated, regardless of symptoms, to prevent progression to pyelonephritis and associated adverse outcomes. 6, 8, 4

Clinical Decision Algorithm

1. Confirm UTI diagnosis with urinalysis and obtain urine culture before starting antibiotics. 7, 4
2. Check gestational age: If < 34 weeks → nitrofurantoin or fosfomycin are preferred; if ≥ 34 weeks → use fosfomycin or beta-lactam (avoid nitrofurantoin). 1, 3
3. Assess drug allergies and contraindications: If penicillin allergy → use nitrofurantoin or fosfomycin; if sulfa allergy → avoid TMP-SMX. 1
4. Prescribe first-line agent:
   • Nitrofurantoin 100 mg PO BID × 5–7 days (if < 34 weeks), OR
   • Fosfomycin 3 g PO single dose (any trimester), OR
   • Amoxicillin-clavulanate 500/125 mg PO BID × 3–7 days (if first-line unavailable). 1, 2, 3, 4
5. Adjust therapy based on culture results once susceptibility data are available (typically 48–72 hours). 7, 4
6. Perform test-of-cure urine culture 1–2 weeks after completing therapy to confirm eradication, as recurrence rates are higher in pregnancy. 4

Common Pitfalls to Avoid

• Do not use fluoroquinolones at any point during pregnancy for UTI treatment, as they are contraindicated due to fetal skeletal concerns. 3, 4
• Do not prescribe TMP-SMX in the first trimester or near term; reserve it only for second-trimester use when culture-proven susceptibility exists and alternatives are unsuitable. 3, 4
• Do not continue nitrofurantoin beyond 34–36 weeks gestation to avoid theoretical neonatal hemolytic anemia risk. 1, 3
• Do not use single-dose regimens other than fosfomycin, as they show inferior efficacy and higher bacteriuria persistence rates. 6
• Do not fail to obtain a test-of-cure culture after treatment, as pregnancy-related physiological changes increase recurrence risk. 4