Indications for Injectable Fosfomycin
Injectable fosfomycin is primarily indicated for complicated urinary tract infections (cUTIs) with or without bacteremia in patients without septic shock, particularly when caused by multidrug-resistant organisms such as ESBL-producing Enterobacterales. 1
Primary Indications
- Injectable fosfomycin is indicated for complicated urinary tract infections (cUTIs) or acute pyelonephritis, including in patients with bacteremia, based on high-certainty evidence from randomized controlled trials 1
- Particularly effective for infections caused by cephalosporin-resistant or ESBL-producing Enterobacterales, with clinical outcomes comparable to carbapenems (meropenem) and piperacillin-tazobactam 1
- Currently under clinical development in the US at a dose of 18 g/day (6g every 8 hours) for the treatment of cUTIs including pyelonephritis 2
Specific Clinical Scenarios
- Most appropriate for patients with cUTIs without septic shock, as safety should be considered in patients at risk for heart failure 1
- Effective for bacteremic cUTIs caused by E. coli, as demonstrated in the FOREST trial 1
- Can be used for treating infections caused by multidrug-resistant gram-negative bacilli, including ESBL-producing and carbapenem-resistant Enterobacterales 1, 3
- Provides an alternative to carbapenems for treating resistant infections, helping with antimicrobial stewardship efforts 2, 3
Dosing Considerations
- For cUTIs, the recommended dosage is 6 grams IV every 8 hours for 7 days (extended to 14 days in patients with concurrent bacteremia) 3
- Injectable fosfomycin has demonstrated superior microbiological eradication rates across resistant phenotypes including ESBL-producing E. coli and Klebsiella spp., CRE, aminoglycoside-resistant, and MDR Gram-negative bacilli 3
Important Clinical Considerations and Cautions
- Safety monitoring is essential, as 8.6% of patients in the FOREST trial developed heart failure when treated with IV fosfomycin (compared to 1.4% with meropenem) 1
- Not recommended for routine use in uncomplicated UTIs, as oral fosfomycin is sufficient for these cases 4, 5
- Should be avoided as monotherapy for severe infections due to concerns about resistance development 6
- Extensive tissue penetration makes it potentially useful for infections of the CNS, soft tissues, bone, lungs, and abscesses, though these are not primary indications 6
Contraindications and Limitations
- Not indicated for patients with septic shock 1
- Caution in patients with heart failure risk factors 1
- Oral fosfomycin (not injectable) is only FDA-approved for uncomplicated UTIs in women 5
- Injectable fosfomycin is not yet FDA-approved in the US but is under clinical development 2
Evidence Quality Assessment
The evidence supporting injectable fosfomycin for cUTIs comes from high-quality randomized controlled trials (ZEUS and FOREST), providing high-certainty evidence for its efficacy in this indication 1. For other potential uses, the evidence is more limited and of lower quality 1, 6.