Can I give injectable (inj) fosfomycin to a patient with Pseudomonas infection sensitive only to fosfomycin?

Injectable Fosfomycin for Pseudomonas Infection

For patients with severe infections caused by multidrug-resistant Pseudomonas aeruginosa that is only susceptible to fosfomycin, injectable fosfomycin should be administered as combination therapy with another in vitro active drug rather than as monotherapy. 1

Treatment Recommendations for Pseudomonas with Limited Susceptibility

First-line Approach

• When treating severe Pseudomonas infections with limited susceptibility options:
  • Use injectable fosfomycin in combination with another active agent 1
  • Avoid fosfomycin monotherapy due to high risk of resistance development 2
  • Consider combination therapy especially for high-bacterial-burden infections 3

Dosing Considerations

• For adults with normal renal function:
  • Fosfomycin IV: 6-8g every 8 hours as part of combination therapy 3
  • Adjust dosing based on renal function and severity of infection
  • Consider continuous infusion for severe infections to maintain adequate drug levels

Combination Options

When Pseudomonas is only susceptible to fosfomycin:

1. If possible, combine with an aminoglycoside (even if in vitro resistance is present) 1
2. Consider high-dose extended-infusion meropenem as part of combination therapy if MIC ≤8 mg/L 1
3. For synergistic effect, fosfomycin plus meropenem has shown significant bacterial killing and resistance suppression 3

Evidence Quality and Clinical Considerations

The ESCMID guidelines (2022) specifically address this scenario, recommending combination therapy when treating severe infections caused by CRPA with polymyxins, aminoglycosides, or fosfomycin 1. This recommendation is based on very low-quality evidence but represents the current expert consensus.

Research studies support this approach:

• Monotherapy with fosfomycin against Pseudomonas shows moderate killing initially but rapid regrowth and resistance development within 24 hours 2
• Hollow-fiber infection models demonstrate that fosfomycin plus meropenem combination provides >6 log10 CFU/ml bacterial killing and prevents resistance emergence 3

Special Considerations

Monitoring

• Monitor electrolytes closely, especially potassium levels, as severe hypokalemia can occur with IV fosfomycin 1
• Follow renal function throughout treatment
• Consider therapeutic drug monitoring if available

Duration of Therapy

• Duration should be determined by clinical response, source control, and infection site
• For severe infections, typically 10-14 days of therapy is required

Pitfalls and Caveats

1. Resistance development: Monotherapy with fosfomycin against Pseudomonas almost invariably leads to resistance 2
2. Inoculum effect: High bacterial loads significantly reduce fosfomycin efficacy 2
3. Limited clinical data: Despite in vitro evidence of efficacy, large clinical trials are lacking
4. Availability issues: Injectable fosfomycin may not be readily available in all regions

For non-severe or low-risk Pseudomonas infections, the ESCMID guidelines suggest monotherapy with an in vitro active drug may be appropriate under antibiotic stewardship principles 1, but this does not apply to your scenario with limited susceptibility options.