Will fosfomycin (a broad-spectrum antibiotic) effectively treat both urinary tract infections (UTIs) and sexually transmitted infections (STIs) in a sexually active adult male presenting with painful urethritis?

Fosfomycin Will NOT Cure STIs and Should NOT Be Used for Urethritis in Men

Fosfomycin is effective only for uncomplicated urinary tract infections (UTIs) in women and has no established role in treating sexually transmitted infections (STIs) such as gonorrhea or chlamydia. For a sexually active adult male with painful urethritis, you must treat for both gonorrhea and chlamydia using CDC-recommended regimens, not fosfomycin.

Why Fosfomycin Fails for STIs

No Guideline Support for STI Treatment

• The CDC guidelines for sexually transmitted diseases (1993,1998,2006,2010) consistently recommend doxycycline 100 mg orally twice daily for 7 days as the first-line treatment for nongonococcal urethritis (NGU), with no mention of fosfomycin 1.
• For gonococcal urethritis, the CDC recommends ceftriaxone 250 mg IM plus azithromycin 1 g orally as a single dose, again with no role for fosfomycin 1.
• The only published trial examining fosfomycin for gonococcal urethritis used 3 grams orally on days 1,3, and 5 (a total of 9 grams over 5 days), which is vastly different from the single 3-gram dose approved for UTI 2.

Pharmacologic Limitations

• Fosfomycin achieves therapeutic concentrations only in the urinary tract, with peak urinary levels of 1053-4415 mg/L maintained for 24-48 hours after a single dose 3.
• The drug is not metabolized and is excreted unchanged in urine through glomerular filtration, meaning it does not achieve adequate tissue concentrations in the urethra, prostate, or other sites affected by STIs 3.
• The IDSA explicitly states that fosfomycin is not recommended for complicated UTIs, pyelonephritis, or use in men due to insufficient efficacy data 1, 4.

Correct Treatment Algorithm for Male Urethritis

Step 1: Document Urethritis

• Confirm urethritis by demonstrating ≥5 polymorphonuclear leukocytes per oil immersion field on Gram stain of urethral secretions 1.
• Alternatively, use positive leukocyte esterase test on first-void urine or microscopic examination showing ≥10 WBCs per high-power field 1.

Step 2: Test for Specific Pathogens

• Obtain urethral swab or first-void urine for nucleic acid amplification testing (NAAT) for N. gonorrhoeae and C. trachomatis 1.
• Perform Gram stain of urethral exudate to identify intracellular Gram-negative diplococci (presumptive gonorrhea) 1.

Step 3: Empiric Treatment (Before Test Results)

• For epididymitis or urethritis likely caused by gonorrhea/chlamydia:
  • Ceftriaxone 250 mg IM single dose PLUS doxycycline 100 mg orally twice daily for 10 days 1.
• For nongonococcal urethritis (NGU):
  • Azithromycin 1 g orally single dose OR doxycycline 100 mg orally twice daily for 7 days 1.
• Alternative for tetracycline allergy:
  • Erythromycin base 500 mg orally four times daily for 7 days OR ofloxacin 300 mg orally twice daily for 7 days 1.

Step 4: Partner Management

• All sex partners within the preceding 60 days must be evaluated and treated empirically 1.
• Instruct the patient to abstain from sexual intercourse for 7 days after single-dose therapy or until completion of 7-day regimen 1.

When Fosfomycin IS Appropriate

Uncomplicated Cystitis in Women Only

• Fosfomycin 3 grams orally as a single dose is a first-line agent for uncomplicated cystitis in women, with clinical cure rates of 91% and microbiological cure rates of 80% 1, 5.
• It is particularly useful when local resistance to trimethoprim-sulfamethoxazole exceeds 20% or for patients with multidrug-resistant pathogens 1, 4.

Complicated UTI (Off-Label, Salvage Only)

• The IDSA suggests considering 3 grams orally every 48-72 hours for a total of 3 doses for complicated lower UTI when first-line agents have failed, though this is based on low-quality evidence 4.
• This multi-dose regimen is not FDA-approved and should only be used as salvage therapy 4.

Critical Pitfalls to Avoid

• Never use fosfomycin for male urethritis or STIs—there is no guideline support, and the single-dose regimen achieves therapeutic concentrations only in urine, not urethral tissue 4, 5.
• Do not treat urethritis empirically without documenting inflammation—symptoms alone are insufficient for treatment 1.
• Always treat for both gonorrhea and chlamydia in sexually active men under 35 years with urethritis, as coinfection is common 1.
• Fosfomycin resistance is increasing—while current susceptibility remains high (99-100% for ESBL-producing organisms), resistance patterns vary geographically 6, 7, 8.