Can I treat uncomplicated acute cystitis in a healthy adult woman with a single 3‑gram dose of fosfomycin?

Fosfomycin for Uncomplicated Acute Cystitis in Women

Yes, a single 3-gram oral dose of fosfomycin trometamol is an appropriate first-line treatment for uncomplicated acute cystitis in healthy adult women. 1, 2, 3

Efficacy and Position in Treatment Algorithm

• Fosfomycin achieves approximately 91% clinical cure rates for uncomplicated cystitis, with therapeutic urinary concentrations maintained for 24–48 hours after a single dose. 2
• The European Association of Urology, American Urological Association, and Infectious Diseases Society of America all recommend fosfomycin as a first-line option for uncomplicated cystitis in women. 2
• Fosfomycin is particularly appropriate when local trimethoprim-sulfamethoxazole (TMP-SMX) resistance exceeds 20%, which is increasingly common in many regions. 2
• Resistance rates to fosfomycin remain remarkably low at only 2.6% in initial E. coli infections and 5.7% at 9 months, making it highly reliable for empiric therapy. 2

Comparison with Other First-Line Agents

• Nitrofurantoin 100 mg twice daily for 5 days achieves 93% clinical cure and 88% microbiological eradication—slightly higher bacteriological efficacy than fosfomycin but requires 5 days of twice-daily dosing. 2
• TMP-SMX 160/800 mg twice daily for 3 days provides 93% clinical cure and 94% microbiological eradication when the pathogen is susceptible, but should only be used when local E. coli resistance is <20% and the patient has not received TMP-SMX in the prior 3 months. 2
• Fosfomycin's single-dose convenience significantly improves adherence compared to multi-day regimens, which is a major clinical advantage. 2

Critical Limitations and Contraindications

• Do not use fosfomycin for suspected pyelonephritis or upper urinary tract infections—it lacks sufficient tissue penetration and efficacy data for these conditions. 2, 4
• Fosfomycin is not recommended for men with UTIs due to limited clinical efficacy data in this population; male UTIs are considered complicated and require 7–14 days of therapy with different agents. 4
• Avoid fosfomycin if fever >38°C, flank pain, or costovertebral angle tenderness is present, as these signs suggest pyelonephritis requiring fluoroquinolones or parenteral cephalosporins. 2

Dosing and Administration

• The FDA-approved dose is one 3-gram sachet of fosfomycin tromethamine mixed with water, taken as a single oral dose. 3
• Do not use more than one dose for a single episode of acute cystitis—repeated daily doses did not improve outcomes but increased adverse events. 3
• Fosfomycin may be taken with or without food. 3

Safety Profile and Adverse Effects

• Common adverse effects include diarrhea, nausea, and headache, occurring in 5.6%–28% of patients, but these are generally mild and self-limited. 2
• Fosfomycin causes minimal disruption to intestinal flora compared to fluoroquinolones and broad-spectrum agents, reducing the risk of Clostridioides difficile infection. 2
• Fosfomycin is safe in pregnancy—European guidelines recommend it for asymptomatic bacteriuria in pregnant women. 2
• Use with caution in patients with hypernatremia, cardiac insufficiency, or severe renal insufficiency (eGFR <30 mL/min/1.73 m²), particularly with IV formulations. 2

When to Obtain Urine Culture

• Routine urine culture is not required for otherwise healthy women with typical cystitis symptoms (dysuria, frequency, urgency). 2
• Obtain urine culture and susceptibility testing if:
  • Symptoms persist after completing therapy 2
  • Symptoms recur within 2 weeks 2
  • Fever, flank pain, or systemic signs develop 2
  • Atypical presentation or vaginal discharge is present 2

Management of Treatment Failure

• If symptoms do not improve within 2–3 days or recur within 2 weeks, obtain urine culture and switch to a different antibiotic class for a 7-day course (nitrofurantoin, TMP-SMX, or fluoroquinolone based on susceptibility). 2
• Assume the original pathogen is resistant to fosfomycin if treatment fails. 2

Clinical Advantages Over Other Agents

• Single-dose regimen eliminates adherence issues that plague multi-day courses. 2
• Excellent activity against multidrug-resistant organisms, including ESBL-producing E. coli, vancomycin-resistant Enterococcus (VRE), and MRSA causing uncomplicated cystitis. 2
• No renal dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). 2

Common Pitfalls to Avoid

• Do not prescribe fosfomycin for men—male UTIs require longer courses (7–14 days) with agents that penetrate prostatic tissue. 4
• Do not use fosfomycin empirically if pyelonephritis cannot be excluded—upper tract infections require different antibiotics with better tissue penetration. 2
• Do not repeat fosfomycin dosing—the FDA label explicitly warns against multiple doses for a single episode. 3
• Verify the patient has uncomplicated cystitis (no fever, flank pain, pregnancy, catheter, immunosuppression, or anatomic abnormalities) before prescribing single-dose therapy. 1, 2