Can intravenous fosfomycin be used to treat a Klebsiella wound infection that is susceptible (minimum inhibitory concentration ≤ 32 mg/L) with adequate surgical debridement, and what dosing regimen, combination therapy, and monitoring are recommended?

Fosfomycin for Klebsiella Wound Infection

Yes, intravenous fosfomycin can be used for Klebsiella wound infection, but only in combination therapy with adequate surgical debridement, and only after confirming susceptibility testing shows MIC ≤32 mg/L. 1, 2

Mandatory Pre-Treatment Requirements

Before initiating fosfomycin therapy, you must:

• Confirm fosfomycin susceptibility through laboratory testing – Susceptibility rates in Klebsiella pneumoniae vary from 39% to 99% depending on local epidemiology, making empiric use inappropriate 2, 3
• Explicitly request fosfomycin susceptibility testing from your laboratory, as many facilities do not perform this routinely 2
• Perform surgical debridement of the wound infection, as source control is essential for treatment success 4
• Screen for contraindications – Avoid fosfomycin in patients with hypernatremia, cardiac insufficiency, or renal insufficiency due to high sodium content of IV formulation 1, 2, 3

Combination Therapy Partners (Choose One)

Fosfomycin must never be used as monotherapy for wound infections. Select a combination partner based on susceptibility:

First-Line Options:

• Gentamicin 1 mg/kg IV every 8 hours – Reduces clinical treatment failures by 417 per 1,000 patients (RR=0.41) and mortality by 59 per 1,000 patients (RR=0.86) when combined with fosfomycin 2

  • Limit duration to ≤7 days to minimize nephrotoxicity 2
  • Therapeutic drug monitoring strongly recommended 2

• Amikacin – Demonstrates persistent bactericidal effect when combined with fosfomycin against KPC-producing Klebsiella 5

  • Therapeutic drug monitoring strongly recommended 2

Alternative Options:

• Tigecycline – Achieved 54.2% clinical efficacy and 56.3% bacterial eradication in ICU patients with carbapenem-resistant Klebsiella 2
• Polymyxin B (colistin) – Frequently studied combination for resistant Klebsiella, requires therapeutic drug monitoring 2, 6
• High-dose extended-infusion meropenem – Can be effective through synergistic activity even against carbapenem-resistant strains when MIC ≤8 mg/L 4, 2

Dosing Regimen

• Fosfomycin: 16-24 g/day IV for Gram-negative infections (divided into doses every 6-8 hours) 7
• Higher doses (up to 24 g/day) are required for Gram-negative bacteria compared to Gram-positive organisms 7
• The pharmacodynamic target is AUC/MIC ratio 7

Critical Monitoring Parameters

• Serum potassium levels – Severe reversible hypokalemia occurs in approximately 6% of ICU patients receiving IV fosfomycin 2, 3
• Cardiac function – Heart failure developed in 8.6% of patients receiving IV fosfomycin versus 1.4% with meropenem in clinical trials 2
• Renal function – Particularly important when using aminoglycoside combinations 2
• Clinical response – Assess wound healing, fever curve, and inflammatory markers 4

Duration of Therapy

• 5-10 days for uncomplicated wound infections with appropriate source control 4
• Duration should be guided by clinical response, adequacy of debridement, and resolution of systemic signs of infection 4

Common Pitfalls to Avoid

• Do not use fosfomycin empirically – Therapy should only commence after confirmed susceptibility because resistance patterns are highly variable 2
• Do not use oral fosfomycin formulation – Wound infections require IV formulation in combination therapy, not the single-dose oral preparation 1
• Do not assume susceptibility – Resistance genes (particularly FosA-like) are increasingly prevalent in carbapenem-resistant Klebsiella strains 2, 3
• Do not use monotherapy – High rates of treatment failure and rapid resistance development occur with fosfomycin monotherapy 7, 6
• Do not overlook source control – Inadequate debridement is a major cause of treatment failure regardless of antibiotic choice 4

Evidence Quality Considerations

The evidence supporting fosfomycin for multidrug-resistant Gram-negative wound infections is predominantly observational with very low certainty 2. However, pooled data suggest fosfomycin-containing combinations reduce mortality by 114 per 1,000 patients (RR=0.55) compared to other therapeutic strategies 2. The clinical benefits likely outweigh potential harms when treating resistant Klebsiella infections with limited alternatives 2.