Fosfomycin for E. coli UTI
Direct Answer
A single 3-gram oral dose of fosfomycin trometamol is appropriate as first-line therapy for uncomplicated E. coli cystitis in non-pregnant adult women, achieving approximately 91% clinical cure rates with the convenience of single-dose administration and minimal collateral damage to intestinal flora. 1
Standard Dosing and Administration
Administer fosfomycin trometamol 3 grams as a single oral dose for acute uncomplicated cystitis in adult women, mixed with water before ingesting (never taken in dry form). 1, 2
This single dose provides therapeutic urinary concentrations (>128 mg/L) for 24–48 hours, sufficient to eradicate most uropathogens including E. coli. 1, 3
Clinical cure rates reach approximately 91% at 5–9 days post-treatment, with microbiological eradication in 78–83% of cases. 1
Position in Treatment Algorithm
When to Use Fosfomycin as First-Line
Fosfomycin is recommended as first-line therapy alongside nitrofurantoin and trimethoprim-sulfamethoxazole (TMP-SMX) for uncomplicated cystitis in women by the American Urological Association (Grade B evidence), European Association of Urology, and American College of Physicians. 1
Particularly appropriate when TMP-SMX resistance exceeds 20% in the community, as E. coli resistance to fosfomycin remains remarkably low at only 2.6% in initial infections. 1
Fosfomycin offers minimal disruption to intestinal flora compared to fluoroquinolones and cephalosporins, reducing risk of C. difficile infection and other collateral damage. 1
When NOT to Use Fosfomycin
Do not use fosfomycin for pyelonephritis or upper urinary tract infections due to insufficient efficacy data and inadequate tissue penetration; fluoroquinolones or β-lactams are preferred for these conditions. 1
Do not use fosfomycin routinely in men with UTIs due to limited clinical efficacy data in this population; the European Association of Urology explicitly does not recommend it for male patients. 4
Do not use fosfomycin for complicated UTIs (those with structural abnormalities, immunosuppression, or systemic symptoms); these require longer courses of alternative agents or parenteral therapy. 1
Dosing Modifications for Special Populations
Pregnancy
Fosfomycin is safe in pregnancy (Category B) and is recommended for both asymptomatic bacteriuria and symptomatic UTI by the European Association of Urology and American College of Obstetricians and Gynecologists. 1, 5
Standard single 3-gram dose is appropriate throughout all trimesters for uncomplicated lower UTI or asymptomatic bacteriuria. 5
The European Urology guidelines recommend fosfomycin as first-line alongside nitrofurantoin for first-trimester UTI, with cephalosporins as alternatives. 5
Always obtain urine culture before treatment in pregnancy and perform follow-up culture 1–2 weeks after completion to confirm cure. 5
Critical context: Untreated bacteriuria increases pyelonephritis risk 20–30 fold (from 1–4% to 20–35%) in pregnant women, making prompt treatment essential. 5
Renal Impairment
For mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²), use standard 3-gram dose without adjustment. 1
For severe renal impairment (eGFR <30 mL/min/1.73 m²), use fosfomycin with caution, as elimination half-life increases from 5.7 hours to 40–50 hours in anuric patients. 1
Monitor electrolytes during and after treatment in patients with renal dysfunction, as fosfomycin can cause hypokalemia, hypocalcemia, hypomagnesemia, and hypernatremia. 1
Avoid in patients with hypernatremia, cardiac insufficiency, or severe renal insufficiency, particularly when considering IV formulations. 1
Comparative Efficacy with Other First-Line Agents
Fosfomycin vs. Nitrofurantoin
Nitrofurantoin 100 mg twice daily for 5 days achieves approximately 93% clinical cure and 88% microbiological eradication, slightly superior to fosfomycin's bacteriological efficacy. 1
However, fosfomycin offers single-dose convenience that improves adherence compared to 5-day regimens, with comparable overall clinical outcomes. 1
A 2022 meta-analysis found no significant differences in clinical cure (RR 0.95% CI 0.81–1.12) or microbiological cure (RR 0.96,95% CI 0.84–1.08) between fosfomycin and nitrofurantoin. 6
Fosfomycin vs. TMP-SMX
TMP-SMX 160/800 mg twice daily for 3 days provides 93% clinical cure and 94% microbiological eradication when the organism is susceptible. 1
The Infectious Diseases Society of America notes fosfomycin has somewhat inferior efficacy compared to 3-day TMP-SMX or fluoroquinolones based on FDA submission data, but it remains appropriate first-line due to minimal resistance and collateral damage. 1
TMP-SMX should only be used when local E. coli resistance is <20% and the patient has not received TMP-SMX in the prior 3 months. 1
Fosfomycin vs. Fluoroquinolones
Fluoroquinolones (ciprofloxacin 250 mg twice daily or levofloxacin 250 mg once daily for 3 days) achieve approximately 90% clinical and 91% microbiological cure rates. 1
Fluoroquinolones should be reserved for culture-proven resistant organisms or documented failure of first-line therapy, not used empirically for uncomplicated cystitis due to serious adverse effects and need to preserve these agents. 1
Management of Treatment Failure
If symptoms do not resolve by the end of treatment or recur within 2 weeks, obtain urine culture and antimicrobial susceptibility testing immediately. 1
Switch to a different antibiotic class for a 7-day course (not the original short regimen), assuming the original pathogen is resistant to fosfomycin. 1
Consider alternative agents: nitrofurantoin for 5 days, TMP-SMX for 3 days, or fluoroquinolones for 3 days based on culture results. 1
Safety Profile and Adverse Effects
Most common adverse events are gastrointestinal: diarrhea, nausea, and vomiting, occurring in 5.6–28% of patients. 1, 3
These adverse events are generally transient, mild, and self-limiting, with no serious drug-related adverse events reported in clinical trials. 7
The incidence of adverse events is slightly higher with fosfomycin compared to nitrofurantoin (RR 1.05,95% CI 0.59–1.87), though not statistically significant. 6
Critical Clinical Pitfalls to Avoid
Do not use fosfomycin for suspected pyelonephritis (fever, flank pain, costovertebral angle tenderness); switch to fluoroquinolones or parenteral cephalosporins immediately. 1
Do not treat asymptomatic bacteriuria in non-pregnant women, as this promotes unnecessary antimicrobial use and resistance without clinical benefit; pregnancy is the only exception. 1
Do not obtain routine post-treatment urinalysis or urine cultures for asymptomatic patients who have completed therapy successfully. 1
Do not use fosfomycin in men with UTI due to lack of efficacy data; male UTIs require 7–14 days of treatment with guideline-recommended agents. 4
Verify the patient has uncomplicated cystitis (no fever, no flank pain, no structural abnormalities, no recent instrumentation) before prescribing single-dose fosfomycin. 1