Is fosfomycin a good antibiotic for urinary tract infections (UTIs) caused by non-fermenting gram-negative rods?

Fosfomycin for UTI with Non-Fermenting Gram-Negative Rods

Fosfomycin is NOT a good antibiotic choice for UTIs caused by non-fermenting gram-negative rods (such as Pseudomonas aeruginosa and Acinetobacter species), and should be avoided for this indication.

Primary Evidence Against Use

The available evidence specifically addresses fosfomycin's limitations for non-fermenting organisms:

• Pseudomonas aeruginosa shows significantly higher rates of resistance development compared to Enterobacteriaceae, with only 64.5% susceptibility in one study of non-urinary isolates, and resistance emergence is more frequent both in vitro and in clinical studies 1, 2

• Fosfomycin is specifically recommended only for uncomplicated cystitis in women caused by typical uropathogens (E. coli, Enterococcus), not for infections caused by non-fermenting organisms 3, 4

Why This Matters Clinically

Mechanism of Resistance

Non-fermenting gram-negative rods develop resistance to fosfomycin more readily than Enterobacteriaceae through:

• Loss of active transport mechanisms 5
• Higher mutational frequency during therapy 2
• The biological fitness cost that limits resistance in E. coli does not apply as effectively to Pseudomonas 2

Guideline Restrictions

Major guidelines explicitly limit fosfomycin use:

• The European Association of Urology restricts fosfomycin to uncomplicated cystitis only, specifically excluding complicated UTIs and pyelonephritis 3
• Fosfomycin should NOT be used for complicated UTIs or pyelonephritis caused by any pathogen, including resistant organisms 4
• The ESCMID guidelines discuss fosfomycin only in the context of ESBL-producing Enterobacteriaceae, not non-fermenters 6

Alternative Approaches for Non-Fermenters

For UTIs caused by non-fermenting gram-negative rods, consider:

First-Line Options

• Aminoglycosides (gentamicin, amikacin) show moderate-certainty evidence for complicated UTI treatment, though nephrotoxicity risk increases after 7 days 6
• Carbapenems remain standard therapy for susceptible isolates 6

Combination Therapy

• Aminoglycoside-containing combinations may improve cure rates and reduce mortality for carbapenem-resistant organisms 6
• Combination therapy is preferred over monotherapy for serious infections with non-fermenters 6

Critical Pitfalls to Avoid

• Do not use oral fosfomycin for any infection with non-fermenting organisms - it lacks sufficient data and has poor efficacy 3, 4
• Do not rely on fosfomycin for Pseudomonas infections - resistance develops rapidly and susceptibility is only 64.5% even in susceptible populations 1, 2
• Intravenous fosfomycin has only been studied in combination therapy for carbapenem-resistant Enterobacteriaceae, not non-fermenters 6

When Fosfomycin IS Appropriate

Fosfomycin remains an excellent choice for:

• Uncomplicated cystitis in women caused by E. coli or Enterococcus (including VRE) 3
• ESBL-producing Enterobacteriaceae causing uncomplicated lower UTI only 4
• Single 3-gram oral dose provides 24-48 hours of therapeutic urinary concentrations 3, 4