What are the recommended first‑line antibiotics, dosing regimens, and safety considerations for treating an uncomplicated urinary tract infection in a pregnant woman, including alternatives for β‑lactam allergy?

Antibiotic Management of Uncomplicated UTI in Pregnancy

For uncomplicated urinary tract infections in pregnant women, nitrofurantoin 100 mg orally twice daily for 5–7 days, fosfomycin trometamol 3 g as a single oral dose, or amoxicillin 500 mg three times daily for 3–7 days are the recommended first-line regimens, with fosfomycin offering the highest pathogen susceptibility (98–99% for E. coli) and single-dose convenience. 1, 2, 3, 4

First-Line Oral Antibiotics for Pregnant Women

Fosfomycin (Preferred Single-Dose Option)

• Fosfomycin trometamol 3 g as a single oral dose demonstrates 98–99% sensitivity against E. coli (which causes 75–95% of pregnancy UTIs) and 88–89% sensitivity against Klebsiella species across all three trimesters. 4
• The single-dose regimen provides therapeutic urinary concentrations for 24–48 hours, maximizes adherence, and is safe throughout all trimesters of pregnancy. 1, 5, 3, 4
• Fosfomycin is appropriate for both asymptomatic bacteriuria and symptomatic cystitis in pregnancy. 1, 3

Nitrofurantoin (Preferred Multi-Day Option)

• Nitrofurantoin 100 mg orally twice daily for 5–7 days achieves 93–100% sensitivity against Enterococcus species and maintains excellent activity against E. coli throughout pregnancy. 1, 3, 4, 6
• Nitrofurantoin is safe in the first and second trimesters but should be avoided after 36 weeks gestation due to theoretical risk of neonatal hemolytic anemia. 3, 6
• This agent should not be used when estimated glomerular filtration rate is < 30 mL/min/1.73 m². 1

Beta-Lactam Antibiotics

• Amoxicillin 500 mg orally three times daily for 3–7 days provides approximately 80% cure rates for susceptible organisms and is safe throughout all trimesters. 3, 7
• Third-generation cephalosporins (e.g., cefixime) demonstrate high sensitivity against E. coli, excellent safety profiles, and are appropriate when first-line agents are contraindicated. 2, 3
• Amoxicillin-clavulanate is acceptable but should be reserved for culture-proven susceptibility due to variable resistance patterns. 3

Treatment Duration and Regimen Selection

Asymptomatic Bacteriuria

• Single-dose therapy with fosfomycin 3 g or short-course therapy (3–7 days) with nitrofurantoin or beta-lactams is appropriate for asymptomatic bacteriuria detected on screening. 1, 3, 7
• Treatment of asymptomatic bacteriuria reduces the incidence of low birth weight and preterm birth, justifying screening with a single urine culture in the first trimester. 3

Symptomatic Cystitis

• Three-to-seven-day courses are recommended for symptomatic lower UTI in pregnancy, as single-dose regimens (except fosfomycin) show inferior cure rates. 3, 7
• Amoxicillin 500 mg three times daily for 3 days is specifically recommended for symptomatic UTI. 7

Agents to Avoid or Use with Caution

Trimethoprim-Sulfamethoxazole

• Avoid in the first trimester due to theoretical risk of neural tube defects from folate antagonism. 1, 6
• Avoid in the third trimester (especially near term) due to risk of neonatal hyperbilirubinemia and kernicterus. 1, 6
• Despite these restrictions, TMP-SMX may be considered in the second trimester when local E. coli resistance is < 20% and other options are unsuitable. 1

Fluoroquinolones

• Fluoroquinolones are contraindicated throughout pregnancy due to potential cartilage toxicity in the developing fetus and should be reserved only for life-threatening infections when no alternatives exist. 3

Aminoglycosides

• Aminoglycosides carry risk of ototoxicity and nephrotoxicity to the fetus and should be reserved for severe pyelonephritis requiring parenteral therapy. 3

Management of Acute Pyelonephritis in Pregnancy

• Hospitalization with parenteral antibiotics is required for acute pyelonephritis, which is associated with increased maternal complications, preterm delivery, and low birth weight. 3
• Preferred parenteral regimens include:
  • Amoxicillin combined with an aminoglycoside (gentamicin or amikacin)
  • Third-generation cephalosporins (ceftriaxone or cefotaxime)
  • Carbapenems for severe or resistant infections 3
• Pivmecillinam is efficient against pyelonephritis and is commonly used in Nordic countries, though availability varies by region. 6

Diagnostic and Follow-Up Recommendations

Screening for Asymptomatic Bacteriuria

• Obtain a single urine culture in the first trimester (ideally at 12–16 weeks) to screen for asymptomatic bacteriuria. 3
• Routine screening beyond the first trimester is not recommended unless risk factors for recurrent UTI are present. 3

Post-Treatment Urine Culture

• Repeat urine culture 7 days after completing therapy to document microbiological cure or identify treatment failure. 7
• If symptoms persist or recur within 2–4 weeks, obtain urine culture with susceptibility testing and switch to a different antibiotic class for a 7-day course. 1

When to Obtain Urine Culture Before Treatment

• Urine culture is mandatory in all pregnant women with urinary symptoms before initiating empiric therapy. 1, 3
• Culture-directed therapy should replace empiric treatment once susceptibility results are available. 3

Beta-Lactam Allergy Alternatives

• For patients with documented penicillin allergy, fosfomycin 3 g single dose or nitrofurantoin 100 mg twice daily for 5–7 days are the preferred alternatives. 1, 3, 4
• Third-generation cephalosporins may be used cautiously in patients with non-severe penicillin allergy (e.g., rash without anaphylaxis), as cross-reactivity is low (< 3%). 2, 3
• Avoid all beta-lactams in patients with documented IgE-mediated anaphylaxis to penicillins. 3

Common Clinical Pitfalls

• Do not use nitrofurantoin after 36 weeks gestation due to risk of neonatal hemolysis. 3, 6
• Do not use trimethoprim-sulfamethoxazole in the first or third trimesters due to teratogenic and neonatal risks. 1, 6
• Do not rely on ampicillin or amoxicillin alone for empiric therapy without culture confirmation, as E. coli resistance exceeds 55% in many regions. 1, 6
• Do not treat asymptomatic bacteriuria without documented positive urine culture, as overtreatment promotes antimicrobial resistance. 3
• Do not use fosfomycin for suspected pyelonephritis, as it lacks adequate tissue penetration for upper urinary tract infections. 1, 5