What is the recommended dose of Fosfomycin for treating Morganella and Pseudomonas infections?

Fosfomycin Dosing for Morganella and Pseudomonas Infections

For Pseudomonas and Morganella infections, intravenous fosfomycin should be administered at a dose of 12-24 g/day divided in 3-4 doses, while oral fosfomycin is not recommended for Pseudomonas infections due to high treatment failure rates and rapid resistance development.

Dosing Recommendations by Route of Administration

Intravenous Fosfomycin

For serious systemic infections caused by multidrug-resistant organisms including Pseudomonas and Morganella:

• Adult dosage: 12-24 g/day divided in 3-4 doses 1
• Administration: 4-hour infusion is recommended to optimize pharmacokinetic/pharmacodynamic properties 1
• Duration: Individualized based on infection site, source control, and clinical response, typically 10-14 days for serious infections 1

Higher doses (18-24 g/day) are recommended for:

• Critically ill patients
• Severe infections (e.g., bacteremia, pneumonia)
• Infections caused by organisms with higher MICs

Oral Fosfomycin (Fosfomycin Trometamol)

• Not recommended for Pseudomonas infections due to high treatment failure rates and rapid resistance development 2
• For uncomplicated urinary tract infections in adults:
  • Age <12 years: 2000 mg as a single dose 1
  • Age ≥12 years: 3000 mg as a single dose 1

Special Considerations for Specific Pathogens

Pseudomonas aeruginosa

• Oral fosfomycin is ineffective against Pseudomonas urinary tract infections despite high urinary concentrations 2
• Resistance emergence was observed in the majority of isolates and worsened with prolonged therapy 2
• Intravenous fosfomycin should always be used in combination therapy for Pseudomonas infections, typically with colistin or tigecycline 3

Morganella morganii

• Limited specific data for Morganella
• Follow general recommendations for multidrug-resistant gram-negative infections
• Combination therapy is typically recommended

Combination Therapy

Fosfomycin should be used in combination with other active antimicrobials when treating serious infections caused by multidrug-resistant pathogens:

• Combination with colistin or tigecycline is common for critically ill patients 3
• The synergistic effect helps prevent resistance development
• For Pseudomonas specifically, combination therapy is essential due to high risk of resistance development during monotherapy 3, 2

Monitoring and Safety Considerations

• Electrolyte monitoring: Regular monitoring of serum potassium is essential as reversible hypokalemia is the main adverse event 3
• Renal function: Dose adjustment may be required in patients with renal impairment
• Resistance development: Monitor for emergence of resistance, particularly with Pseudomonas infections 2

Clinical Efficacy

In critically ill patients with extensively drug-resistant or pandrug-resistant infections:

• Clinical success rate of 54.2% at day 14 when fosfomycin was used (primarily in combination therapy) 3
• Bacterial eradication observed in 56.3% of cases 3
• Resistance development occurred in only 3 cases in a study of 48 patients 3

Important Caveats

• Baseline MIC ≥8 mg/L with a high-level resistant subpopulation predicts post-exposure emergence of resistance 2
• PK/PD target of fAUC0-24/MIC >5000 is associated with optimal killing at 72 hours 2
• Oral fosfomycin should not be used for multiple-dose regimens against Pseudomonas despite theoretical pharmacokinetic models suggesting efficacy 4
• Always confirm susceptibility before initiating therapy

Fosfomycin represents an important option in the limited armamentarium against multidrug-resistant gram-negative infections, but must be used judiciously with appropriate dosing and combination therapy to maximize efficacy and minimize resistance development.