Fosfomycin Administration for Urinary Tract Infections and Systemic Infections
Oral Fosfomycin for Uncomplicated Lower UTI
For uncomplicated cystitis in women, administer fosfomycin tromethamine 3 grams as a single oral dose, which provides therapeutic urinary concentrations for 24–48 hours and achieves approximately 91% clinical cure rates. 1
Standard Oral Dosing
- Dissolve the entire 3-gram sachet in 90–120 mL of water and consume immediately on an empty stomach, preferably at bedtime after emptying the bladder 2
- The single dose maintains urinary concentrations >128 mg/L for 24–48 hours, sufficient to inhibit most uropathogens 2
- Do not repeat the dose for uncomplicated cystitis; the single-dose regimen is the evidence-based standard 1
- Oral bioavailability is 34–41%, with peak urinary concentrations occurring within 4 hours 2
When Oral Fosfomycin Is Appropriate
- First-line therapy for uncomplicated cystitis in women caused by E. coli, Enterococcus (including VRE), or other typical uropathogens 1, 3
- Particularly useful when local trimethoprim-sulfamethoxazole resistance exceeds 20% 1
- Safe in pregnancy for asymptomatic bacteriuria 1, 3
- Effective against ESBL-producing E. coli causing uncomplicated lower UTI 4
Critical Contraindications for Oral Fosfomycin
- Never use for pyelonephritis or upper urinary tract infections—insufficient tissue penetration and lack of efficacy data 5, 1, 4
- Never use for complicated UTIs—restricted to uncomplicated cystitis only 4
- Never use in men with UTI—limited efficacy data in this population 1
- Avoid when eGFR <30 mL/min/1.73 m² if alternative agents are available 1
Intravenous Fosfomycin for Systemic Infections
For systemic infections caused by carbapenem-resistant Gram-negative bacilli susceptible to fosfomycin, administer IV fosfomycin as combination therapy with a loading dose of 8 grams followed by 16–24 grams daily via continuous infusion. 5, 6
IV Dosing Regimen for Normal Renal Function
- Loading dose: 8 grams IV over 1 hour 6
- Maintenance: 16–24 grams per day as continuous infusion 6
- Alternative intermittent dosing: 4–8 grams IV every 6–8 hours (total daily dose 12–24 grams) 6
- Always combine with another active antibiotic to prevent emergence of resistance 5, 6
Mandatory Pre-Treatment Requirements
- Confirm fosfomycin susceptibility through antimicrobial susceptibility testing or demonstrate synergistic effect through combination testing before initiating therapy 5
- Obtain baseline electrolytes, particularly sodium, potassium, calcium, and magnesium 1
- Assess cardiac and renal function 5
Absolute Contraindications for IV Fosfomycin
- Hypernatremia—each gram of IV fosfomycin contains 14.5 mEq of sodium 5, 1
- Cardiac insufficiency—high sodium load poses decompensation risk 5
- Severe renal insufficiency—elimination half-life increases from 5.7 hours to 40–50 hours in anuric patients 1
Indications for IV Fosfomycin
- Carbapenem-resistant Enterobacteriaceae (CRE) infections when the isolate is susceptible to fosfomycin 5
- Bloodstream infections, sepsis, urinary tract infections, or multiple-site infections caused by susceptible CRE 5
- Only as combination therapy—never as monotherapy for systemic infections 5, 7
Renal Dose Adjustments
Oral Fosfomycin
- eGFR ≥30 mL/min/1.73 m²: No dose adjustment required; use standard 3-gram single dose 1
- eGFR <30 mL/min/1.73 m²: Use with caution; consider alternative agents (nitrofurantoin is contraindicated at this level) 1
IV Fosfomycin
- Normal renal function (CrCl >80 mL/min): 16–24 grams daily 6
- Renal impairment: Specific dosing regimens for renal insufficiency require further investigation; current evidence is insufficient to provide clear recommendations 6
- Anuric patients: Elimination half-life extends to 40–50 hours; avoid use 1
Monitoring Requirements for IV Fosfomycin
Electrolyte Monitoring
- Monitor sodium, potassium, calcium, and magnesium during and after treatment 1
- Hypokalemia, hypocalcemia, hypomagnesemia, and hypernatremia are documented adverse effects 5, 1
- Reversible severe hypokalemia occurred in 3 of 48 ICU patients in one study 5
Therapeutic Drug Monitoring
- Consider TDM for critically ill patients receiving fosfomycin for CRGNB infections, particularly when combined with polymyxins, aminoglycosides, or carbapenems 5
- TDM is especially important for infections at difficult-to-reach sites (CNS, bloodstream) or in patients with organ dysfunction 5
Common Pitfalls and How to Avoid Them
Pitfall 1: Using Oral Fosfomycin for Pyelonephritis
- Avoid: Oral fosfomycin lacks efficacy data for upper UTI 5, 1, 4
- Instead: Use fluoroquinolones (ciprofloxacin, levofloxacin) or β-lactams for pyelonephritis 5, 1
Pitfall 2: IV Fosfomycin Monotherapy
- Avoid: Monotherapy leads to rapid emergence of resistance 5, 6, 7
- Instead: Always combine with tigecycline, polymyxin, carbapenem, or aminoglycoside based on susceptibility 5
Pitfall 3: Ignoring Sodium Load in Cardiac Patients
- Avoid: Each gram contains 14.5 mEq sodium; 24 grams daily = 348 mEq sodium 1
- Instead: Screen for cardiac insufficiency and hypernatremia before prescribing IV fosfomycin 5
Pitfall 4: Repeating Oral Doses Without Evidence
- Avoid: Multiple 3-gram doses for uncomplicated cystitis lack supporting data 1
- Instead: If symptoms persist after 2–3 days, obtain urine culture and switch to a different agent (nitrofurantoin 5 days, TMP-SMX 3 days, or fluoroquinolone 3 days) 1
Pitfall 5: Using Fosfomycin for Non-Fermenting Organisms
- Avoid: Oral fosfomycin is ineffective against Pseudomonas aeruginosa and other non-fermenters 4
- Instead: Use aminoglycosides, carbapenems, or combination therapy for non-fermenting Gram-negative rods 4
Adverse Effects
Oral Fosfomycin
- Diarrhea, nausea, vomiting (4.3–5.6% incidence) 1, 8
- Transient, mild, and self-limiting gastrointestinal symptoms 2, 8