Is additional antibiotic coverage with Septra (sulfamethoxazole and trimethoprim) necessary when a urine culture is positive for Escherichia coli (E. coli) after a single dose of Fosfomycin?

Single-Dose Fosfomycin for E. coli UTI: No Additional Septra Required

No, you do not need to prescribe Septra (trimethoprim-sulfamethoxazole) after a single dose of fosfomycin for an E. coli-positive urine culture in uncomplicated cystitis—fosfomycin alone is sufficient as a complete first-line treatment. 1

Rationale for Fosfomycin Monotherapy

Fosfomycin as Complete Treatment

• Single 3-gram oral dose of fosfomycin provides therapeutic urinary concentrations for 24-48 hours, which is adequate for complete treatment of uncomplicated UTIs 1
• The European Association of Urology and American Urological Association both recommend fosfomycin as a first-line monotherapy option for uncomplicated cystitis in women, with strong evidence (Grade B) supporting its use as a standalone treatment 1, 2
• Clinical recovery rates and bacteriological eradication rates with single-dose fosfomycin are comparable to multi-day regimens of other first-line agents 1

E. coli Susceptibility

• Fosfomycin displays broad-spectrum activity against E. coli, including ESBL-producing and multidrug-resistant strains, with resistance rates remaining very low (<1%) 2
• All 100 randomly selected ESBL-producing E. coli clinical isolates tested at a major tertiary care hospital were susceptible to fosfomycin 3
• Fosfomycin achieves peak urinary concentrations of approximately 4000 µg/mL and remains at concentrations >100 µg/mL for 48 hours after a single 3-gram oral dose 2

When Fosfomycin Alone is Appropriate

Uncomplicated Cystitis

• Fosfomycin monotherapy is specifically indicated for uncomplicated cystitis in women with E. coli infection 1
• Clinical success rates at 48 hours range from 74.8% to 89.9% for physician-diagnosed and NHSN-defined UTIs, respectively 3
• Recurrent infections occur in only 4.3% of cases, and mild adverse events are observed in 2.0% 3

Follow-Up Considerations

• Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients 1
• If symptoms do not resolve by the end of treatment or recur within 2 weeks, then urine culture and antimicrobial susceptibility testing should be performed 1

When Additional Treatment May Be Needed

Contraindications to Fosfomycin Monotherapy

• Do not use fosfomycin alone for pyelonephritis, complicated UTIs, or UTIs in men—these require different antibiotic regimens 1
• For febrile UTIs or pyelonephritis, fluoroquinolones and cephalosporins are preferred for oral treatment 1
• Complicated UTIs requiring fosfomycin may need intravenous formulation rather than oral 1

When Septra Would Be Considered

• Septra (trimethoprim-sulfamethoxazole) would only be considered as an alternative first-line agent if fosfomycin is contraindicated or unavailable 4
• However, high rates of resistance to trimethoprim-sulfamethoxazole preclude its use as empiric treatment in many communities, particularly in patients recently exposed to it or at risk for ESBL-producing organisms 4
• Approximately 30% of isolated gram-negative bacteria in some populations are resistant to trimethoprim-sulfamethoxazole, and 70% of quinolone-resistant gram-negative bacteria are also resistant to it 5

Common Pitfalls to Avoid

• Do not add Septra "just to be safe" after fosfomycin—this represents unnecessary antibiotic exposure and increases risk of adverse effects and resistance development 1, 3
• Do not confuse uncomplicated cystitis with pyelonephritis or complicated UTI—fosfomycin monotherapy is only appropriate for the former 1
• Do not prescribe routine follow-up cultures in asymptomatic patients, as this leads to unnecessary treatment of asymptomatic bacteriuria 1
• The single-dose convenience of fosfomycin improves adherence compared to 3-7 day regimens and has minimal collateral damage to intestinal flora 1