What is the recommended dosing, safety considerations (including pregnancy and renal impairment), and alternative therapies for using fosfomycin to treat an uncomplicated urinary tract infection in a healthy adult woman?

Fosfomycin for Uncomplicated Urinary Tract Infections

Administer fosfomycin trometamol 3 grams as a single oral dose for acute uncomplicated cystitis in adult women—this is a first-line therapy with comparable clinical efficacy to other recommended agents and the convenience of single-dose administration. 1, 2

Standard Dosing and Administration

• The recommended dose is fosfomycin trometamol 3 grams as a single oral dose. 1, 2
• This single dose provides therapeutic urinary concentrations for 24-48 hours, sufficient to eradicate most uropathogens. 2
• Clinical cure is achieved in approximately 91% of patients 5-9 days after treatment, with microbiological eradication in 78-83% of cases. 2
• Do not use multiple dosing for uncomplicated cystitis—the single 3-gram dose is the evidence-based regimen. 2

Position in Treatment Algorithm

Fosfomycin is recommended as first-line therapy alongside nitrofurantoin and trimethoprim-sulfamethoxazole (TMP-SMX) for uncomplicated cystitis in women. 1, 2

• Use fosfomycin when TMP-SMX resistance exceeds 20% in your community or when the patient has used TMP-SMX within the previous 3 months. 1, 2
• Fosfomycin has minimal collateral damage to intestinal flora compared to fluoroquinolones and cephalosporins, reducing risk of C. difficile infection. 2
• Resistance rates remain low at only 2.6% in initial E. coli infections. 2

Choosing Between First-Line Agents

• Nitrofurantoin 100 mg twice daily for 5 days provides clinical efficacy of 93% and microbiological efficacy of 88%, but requires multiple doses. 2
• TMP-SMX 160/800 mg twice daily for 3 days offers clinical efficacy of 93% and microbiological efficacy of 94%, but only use when local resistance is <20%. 1, 2
• Fosfomycin offers single-dose convenience that improves adherence, though bacteriological efficacy is somewhat lower than TMP-SMX or fluoroquinolones. 1, 2

Critical Limitations and When NOT to Use Fosfomycin

Do not use fosfomycin for pyelonephritis, complicated UTIs, upper tract infections, or routinely in men—efficacy data is insufficient for these conditions. 1, 2

• Avoid fosfomycin if early pyelonephritis is suspected (fever, flank pain, systemic symptoms). 1
• For pyelonephritis, use fluoroquinolones or cephalosporins instead. 2
• Fosfomycin is not recommended for routine use in men with UTIs due to limited clinical efficacy data. 2

Safety Profile and Adverse Effects

• Common adverse events include diarrhea, nausea, vomiting, and headache, occurring in 5.6%-28% of patients. 2, 3
• These gastrointestinal side effects are generally mild and self-limited. 4
• No serious drug-related adverse events have been reported in clinical trials. 2

Use in Pregnancy

Fosfomycin is safe in pregnancy and is recommended as first-line therapy for both asymptomatic bacteriuria and symptomatic UTI in pregnant women. 2, 5

• Administer the same single 3-gram oral dose for pregnant women. 5
• The European Association of Urology recommends fosfomycin as an acceptable alternative to nitrofurantoin throughout pregnancy. 5
• For asymptomatic bacteriuria in pregnancy, use either standard short-course treatment or single-dose fosfomycin. 2, 5
• Always obtain urine culture before initiating treatment in pregnant women. 5
• Follow-up urine culture 1-2 weeks after completing treatment is recommended to confirm cure. 5

Renal Impairment Considerations

For patients with mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²), use standard dosing without adjustment. 2

• Fosfomycin can be used at standard dosing for CKD stage 3b (eGFR 30-44 mL/min/1.73 m²). 2
• Use with caution in patients with severe renal insufficiency, hypernatremia, or cardiac insufficiency, particularly with IV formulations. 2
• Monitor electrolytes during and after treatment in patients with pre-existing renal dysfunction, as fosfomycin can cause hypokalemia, hypocalcemia, hypomagnesemia, and hypernatremia. 2
• The elimination half-life increases from 5.7 hours to 40-50 hours in anuric patients. 2

Management of Treatment Failure

If symptoms do not improve within 2-3 days or recur within 2 weeks, obtain urine culture with antimicrobial susceptibility testing and assume the organism is resistant to fosfomycin. 2

• Retreat with a 7-day course of an alternative antibiotic: nitrofurantoin for 5 days, TMP-SMX for 3 days, or fluoroquinolones for 3 days. 2
• Do not perform routine post-treatment urinalysis or urine cultures for asymptomatic patients. 2

Activity Against Multidrug-Resistant Organisms

Fosfomycin is highly effective against multidrug-resistant pathogens including ESBL-producing E. coli, vancomycin-resistant Enterococcus (VRE), and MRSA causing uncomplicated cystitis. 2

• Use the same single 3-gram oral dose for VRE-associated uncomplicated UTIs. 2
• Fosfomycin becomes cost-effective when trimethoprim resistance in E. coli exceeds 30-35%. 2

Common Pitfalls to Avoid

• Do not use fosfomycin for suspected pyelonephritis—even mild upper tract involvement requires alternative agents. 1, 2
• Do not use β-lactams (amoxicillin, cephalexin) as first-line empiric therapy—they have lower efficacy and higher resistance rates. 2, 6
• Do not use fluoroquinolones as first-line therapy for uncomplicated cystitis—reserve them for documented resistant pathogens or pyelonephritis due to high adverse-effect risk and promotion of resistance. 2, 6
• Do not delay treatment in pregnant women with symptomatic UTI—this increases risk of pyelonephritis and adverse pregnancy outcomes. 5