What are the clinical indications and dosing recommendations for fosfomycin powder?

Fosfomycin Powder: Clinical Indications and Dosing

Fosfomycin powder (fosfomycin tromethamine) is indicated exclusively for acute uncomplicated cystitis in women, administered as a single 3-gram oral dose mixed with water. 1

Primary Indication: Uncomplicated Cystitis in Women

• Single 3-gram oral dose is the FDA-approved regimen for women ≥18 years with acute uncomplicated lower urinary tract infection (cystitis). 1
• The powder must be dissolved in water before ingestion—never take in dry form—and may be consumed with or without food. 1
• This single dose achieves urinary concentrations >128 mg/L for 24–48 hours, sufficient to eradicate most uropathogens. 2
• Clinical cure occurs in approximately 91% of patients, with microbiological eradication in 78–83% within 5–9 days. 3, 2

When to Choose Fosfomycin Over Other First-Line Agents

• Preferred when local trimethoprim-sulfamethoxazole (TMP-SMX) resistance exceeds 20% in the community, making TMP-SMX empirically inappropriate. 3, 2
• Fosfomycin maintains low resistance rates among E. coli (≈2.6% at initial infection, ≈5.7% at 9 months), making it reliable against multidrug-resistant organisms including ESBL-producing E. coli, vancomycin-resistant Enterococcus (VRE), and MRSA. 3, 2
• The single-dose convenience improves adherence compared to 3–7 day regimens, with minimal disruption to intestinal flora and low risk of C. difficile infection. 3

Absolute Contraindications and Critical Limitations

• Do NOT use for pyelonephritis, upper urinary tract infections, complicated UTIs, or UTIs in men—insufficient efficacy data and high failure rates in these populations. 4, 3, 2
• Avoid in patients with eGFR <30 mL/min/1.73 m² because urinary concentrations become inadequate and elimination half-life extends from 5.7 hours to 40–50 hours. 3, 2
• For upper-tract infections or pyelonephritis, use fluoroquinolones (5-day courses) or beta-lactams (7-day courses) instead. 3, 2

Renal Function Dosing

• No dose adjustment required for eGFR ≥30 mL/min/1.73 m²—standard 3-gram single dose is appropriate. 3, 2
• Patients with CKD stage 3b (eGFR 30–44 mL/min/1.73 m²) can receive standard dosing without modification. 3

Special Populations

Pregnant Women

• Fosfomycin is safe in pregnancy (FDA category B) and is recommended for asymptomatic bacteriuria in pregnant women as standard short-course treatment or single-dose administration. 3, 5

Patients with Cardiac or Electrolyte Disorders

• Use with caution in patients with hypernatremia, cardiac insufficiency, or renal insufficiency, particularly if considering IV formulation (not available in the US). 3
• Monitor electrolytes during treatment, as fosfomycin can cause hypokalemia, hypocalcemia, hypomagnesemia, and hypernatremia. 3

Common Adverse Effects

• Diarrhea, nausea, vomiting, and headache occur in 5.6–28% of patients but are generally mild and self-limited. 3, 2
• Gastrointestinal disturbances are the most commonly reported adverse events. 3

Treatment Failure Management

• If symptoms persist after 2–3 days or recur within 2 weeks, obtain urine culture and susceptibility testing immediately and switch to a different antibiotic class for a 7-day course. 3
• Consider alternative agents: nitrofurantoin 100 mg twice daily for 5 days, TMP-SMX 160/800 mg twice daily for 3 days (if susceptible), or fluoroquinolones for 3 days (reserved for resistant pathogens). 3
• Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients who complete therapy successfully. 3

Alternative First-Line Agents When Fosfomycin Is Unsuitable

• Nitrofurantoin 100 mg orally twice daily for 5 days achieves ≈93% clinical cure and ≈88% microbiological eradication, with resistance rates <1% worldwide. 3, 2
• TMP-SMX 160/800 mg orally twice daily for 3 days provides ≈93% clinical cure and ≈94% microbiological eradication when local E. coli resistance is <20% and the patient has not received TMP-SMX in the prior 3 months. 3, 2

Intravenous Fosfomycin (Not Available in the United States)

• IV fosfomycin disodium (6 g every 8 hours for 7–14 days) is used outside the US for complicated UTIs, acute pyelonephritis, and carbapenem-resistant gram-negative infections in combination therapy. 2
• The ZEUS and FOREST trials demonstrated non-inferiority to piperacillin-tazobactam and meropenem for complicated UTIs and bacteremic UTIs caused by E. coli. 2
• Never use IV fosfomycin as monotherapy for serious infections—always combine with another active agent to prevent rapid resistance development. 2

Key Clinical Pitfalls to Avoid

• Do not prescribe fosfomycin for suspected pyelonephritis—patients with fever >38°C, flank pain, or costovertebral angle tenderness require fluoroquinolones or beta-lactams. 3, 2
• Do not treat asymptomatic bacteriuria in non-pregnant women—treatment offers no benefit and promotes resistance; the only exception is pregnant women and patients before urological procedures breaching the mucosa. 3
• Verify local TMP-SMX resistance patterns before choosing between fosfomycin and TMP-SMX; if data are unavailable, default to fosfomycin or nitrofurantoin. 3