What are the preferred oral antibiotic regimens for uncomplicated acute cystitis in an otherwise healthy pregnant woman?

Antibiotic Selection for Cystitis in Pregnancy

Nitrofurantoin 100 mg orally twice daily for 5 days is the preferred first-line oral antibiotic for uncomplicated acute cystitis in otherwise healthy pregnant women. 1, 2

First-Line Oral Antibiotic Options

Nitrofurantoin (Preferred)

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days achieves clinical cure rates of 87–93% and microbiological eradication rates of 81–92% in pregnant women with uncomplicated cystitis. 1, 2, 3
• This agent demonstrates minimal resistance rates (<1% worldwide) and causes less disruption to intestinal flora compared with fluoroquinolones or broad-spectrum agents, reducing the risk of Clostridioides difficile infection. 1, 2
• Nitrofurantoin is safe throughout pregnancy but must be avoided in the last 3 months (third trimester) due to potential risk of hemolytic anemia in the newborn. 4
• Contraindicated when estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m² because adequate urinary concentrations cannot be achieved. 1, 2

Fosfomycin Trometamol (Excellent Alternative)

• Fosfomycin 3 g as a single oral dose provides 90–95% clinical cure and therapeutic success in pregnant women with acute cystitis. 1, 5, 6
• The single-dose regimen offers superior adherence and convenience, maintaining therapeutic urinary concentrations for 24–48 hours. 1
• Fosfomycin is safe throughout pregnancy and demonstrates low resistance rates (approximately 2.6% in initial infections). 1, 5
• Should not be used when pyelonephritis is suspected (fever, flank pain, costovertebral angle tenderness) due to insufficient tissue penetration. 1, 2

Trimethoprim-Sulfamethoxazole (Conditional Use)

• TMP-SMX 160/800 mg (one double-strength tablet) twice daily for 3 days achieves 90–100% clinical cure when the pathogen is susceptible. 2, 7
• Use only when local E. coli resistance is <20% and the patient has not received TMP-SMX in the preceding 3 months. 1, 2, 7
• Absolutely contraindicated in the last trimester of pregnancy due to risk of kernicterus and hemolytic anemia in the newborn. 1, 7
• Many regions now report TMP-SMX resistance exceeding 20%, making verification of local antibiogram data mandatory before selection. 1, 2

Second-Line Options (When First-Line Agents Cannot Be Used)

Third-Generation Oral Cephalosporins

• Cefixime or other third-generation cephalosporins (ceftibuten, cefpodoxime) for 3–7 days are acceptable alternatives when first-line agents are contraindicated. 8, 5
• Cefixime demonstrates high sensitivity against E. coli (the causative pathogen in 75–95% of cases) and good safety profile in pregnancy. 8
• However, beta-lactams achieve only approximately 89% clinical cure and 82% microbiological eradication, which is significantly inferior to nitrofurantoin or fosfomycin. 1, 2

Amoxicillin-Clavulanate

• Amoxicillin-clavulanate 500/125 mg three times daily for 3–7 days may be used when other options are unsuitable. 2
• Never use amoxicillin or ampicillin alone because worldwide E. coli resistance exceeds 55–67%, resulting in unacceptably high failure rates. 1, 2

Agents to Avoid in Pregnancy

• Fluoroquinolones (ciprofloxacin, levofloxacin) should be avoided during pregnancy due to concerns about cartilage toxicity in the developing fetus, despite high efficacy (93–97% eradication rates). 1, 2
• TMP-SMX in the third trimester is contraindicated due to fetal risk. 1, 7
• Tetracyclines and doxycycline are contraindicated throughout pregnancy. 1

Diagnostic Recommendations

• Urine culture is mandatory in all pregnant women with urinary symptoms to confirm the diagnosis and guide therapy if needed. 2, 8, 6
• Obtain culture and susceptibility testing at the first prenatal visit to screen for asymptomatic bacteriuria, which occurs in 20–40% of pregnant women and can progress to pyelonephritis if untreated. 5
• If symptoms persist after completing therapy or recur within 2–4 weeks, obtain repeat urine culture and switch to a different antibiotic class for a 7-day course. 1, 2

Treatment Algorithm for Pregnant Women with Uncomplicated Cystitis

Step 1: Confirm uncomplicated cystitis

• Dysuria, frequency, urgency, suprapubic discomfort without fever (>38°C), flank pain, or systemic symptoms. 2, 6, 3
• Obtain urine culture in all pregnant patients. 8, 5

Step 2: Assess renal function and trimester

• If eGFR ≥30 mL/min and not in third trimester → prescribe nitrofurantoin 100 mg twice daily for 5 days. 1, 2, 4
• If patient prefers single-dose therapy or adherence is a concern → prescribe fosfomycin 3 g single dose. 1, 5, 6

Step 3: If nitrofurantoin and fosfomycin are contraindicated

• Verify local TMP-SMX resistance is <20% and patient is not in third trimester → prescribe TMP-SMX 160/800 mg twice daily for 3 days. 2, 7
• If TMP-SMX unsuitable → prescribe cefixime or ceftibuten for 3–7 days. 8, 5

Step 4: If symptoms persist or recur

• Obtain urine culture and susceptibility testing immediately. 2, 6
• Switch to a different antibiotic class for a full 7-day course based on culture results. 1, 2

Critical Pitfalls to Avoid

• Do not use TMP-SMX in the third trimester under any circumstances due to fetal risk. 1, 7
• Do not prescribe nitrofurantoin when eGFR <30 mL/min or in the last month of pregnancy. 1, 4
• Do not use fosfomycin if pyelonephritis is suspected (fever, flank pain); switch to parenteral cephalosporin or appropriate oral agent for 7–14 days. 1, 2
• Do not treat asymptomatic bacteriuria without culture confirmation in pregnancy; however, once confirmed, treatment is mandatory to prevent pyelonephritis. 5
• Do not use amoxicillin or ampicillin alone due to resistance rates exceeding 55%. 1, 2
• Do not prescribe TMP-SMX empirically without confirming local resistance is <20%; failure rates increase sharply above this threshold. 1, 2, 7