What is the appropriate outpatient oral therapy for acute uncomplicated cystitis in a woman at 18 weeks gestation?

Management of Acute Uncomplicated Cystitis at 18 Weeks Gestation

Fosfomycin 3 g as a single oral dose is the preferred first-line therapy for acute uncomplicated cystitis at 18 weeks gestation, offering therapeutic urinary concentrations for 24–48 hours with proven safety throughout all trimesters. 1

First-Line Treatment Options

Fosfomycin (Preferred)

• Fosfomycin trometamol 3 g as a single oral dose provides approximately 91% clinical cure, maintains therapeutic urinary concentrations for 24–48 hours, and is safe throughout all trimesters of pregnancy. 1
• The European Urology guidelines specifically recommend fosfomycin for asymptomatic bacteriuria in pregnant women with standard short-course treatment or single-dose administration. 1
• The single-dose regimen maximizes adherence and minimizes antibiotic exposure during pregnancy. 1

Nitrofurantoin (Alternative)

• Nitrofurantoin 100 mg orally twice daily for 5–7 days achieves 93–100% sensitivity against Enterococcus spp. and maintains excellent activity against E. coli throughout pregnancy. 1
• Nitrofurantoin should be avoided when estimated glomerular filtration rate is < 30 mL/min/1.73 m². 1, 2
• The IDSA recommends nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5–7 days as a first-line option for uncomplicated UTIs in women. 2

Amoxicillin (Second-Line)

• Amoxicillin 500 mg orally three times daily for 3–7 days is listed among first-line regimens, offering an approximate 80% cure rate for susceptible organisms and safety in all trimesters. 1
• Ampicillin or amoxicillin alone should not be used empirically because E. coli resistance exceeds 55% in many regions; culture-directed therapy is required. 1

Agents to Avoid in Pregnancy

Trimethoprim-Sulfamethoxazole

• TMP-SMX should be avoided in the first trimester because of a theoretical risk of neural-tube defects and in the third trimester because of the risk of neonatal hyperbilirubinemia and kernicterus. 1
• It may be considered in the second trimester only when local E. coli resistance is < 20% and other agents are unsuitable. 1

Fluoroquinolones

• Fluoroquinolones should be reserved for culture-proven resistant organisms or documented failure of first-line therapy due to serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity). 1

Diagnostic Requirements

Mandatory Urine Culture

• Urine culture must be obtained before initiating empiric therapy in any pregnant woman presenting with urinary symptoms. 1
• This differs from non-pregnant women with uncomplicated cystitis, where routine culture is not required. 1

Post-Treatment Follow-Up

• Post-treatment urine culture should be performed 7 days after completing therapy to confirm microbiological cure or to identify treatment failure. 1
• If symptoms persist or recur within 2–4 weeks, a repeat culture with susceptibility testing and a switch to a different antibiotic class for a 7-day course is advised. 1

Clinical Decision Algorithm

1. Confirm uncomplicated cystitis (dysuria, frequency, urgency without fever > 38°C, flank pain, or systemic symptoms). 1

2. Obtain urine culture before starting empiric therapy (mandatory in pregnancy). 1

3. Prescribe fosfomycin 3 g single dose as first-line therapy at 18 weeks gestation. 1

4. Alternative regimens if fosfomycin is unavailable or contraindicated:

   • Nitrofurantoin 100 mg twice daily for 5–7 days (check renal function first). 1, 2
   • Amoxicillin 500 mg three times daily for 3–7 days (only if culture shows susceptibility). 1

5. Obtain post-treatment culture 7 days after completing therapy to document cure. 1

Critical Contraindications

Fosfomycin Limitations

• Fosfomycin is not appropriate for suspected acute pyelonephritis because it does not achieve adequate tissue concentrations for upper-tract infection. 1
• If fever, flank pain, or systemic symptoms develop, switch to parenteral therapy such as ceftriaxone or a fluoroquinolone. 1

Nitrofurantoin Limitations

• Nitrofurantoin must be avoided when eGFR < 30 mL/min/1.73 m² because adequate urinary concentrations cannot be achieved. 1, 2
• The American Geriatrics Society recommends avoiding nitrofurantoin in patients with creatinine clearance below 30 mL/min due to increased risk of peripheral neuropathy and other serious toxicities. 2

Common Pitfalls to Avoid

• Do not use ampicillin or amoxicillin alone empirically due to high E. coli resistance rates (55–67% worldwide). 1
• Do not treat asymptomatic bacteriuria without a documented positive urine culture, as overtreatment promotes antimicrobial resistance. 1
• Do not use fosfomycin for suspected pyelonephritis because of insufficient tissue penetration. 1
• Do not prescribe TMP-SMX in the first or third trimester due to teratogenic and neonatal risks. 1
• Do not skip post-treatment urine culture in pregnant patients, as documentation of cure is essential. 1