Is a single dose of oral Fosfomycin (Fosfomycin) 1 gram sufficient for a 6-month-old infant with a multi-drug resistant E. coli urinary tract infection?

Fosfomycin Dosing for Multidrug-Resistant E. coli UTI in a 6-Month-Old Infant

A single dose of oral fosfomycin 1 gram is not sufficient for treating a multidrug-resistant E. coli urinary tract infection in a 6-month-old infant, as there are no established dosing recommendations for fosfomycin in infants under 1 year of age.

Appropriate Treatment Options for Pediatric MDR UTI

Age-Based Considerations

• Current guidelines do not provide specific dosing recommendations for fosfomycin in infants under 1 year of age 1
• The pediatric section of the 2022 MDRO treatment guidelines specifically states "No recommendations available" for fosfomycin in children under 12 years 1
• For children under 12 years, the guidelines only list dosing for children 12 years and older (3000 mg as a single dose) 1

Alternative Treatment Options for MDR E. coli UTI in Infants

For a 6-month-old infant with multidrug-resistant E. coli UTI, the following treatment options are more appropriate:

1. First-line options:

   • Amikacin: 5-7.5 mg/kg/dose IV q8h or 15-22.5 mg/kg/dose IV q24h 1
   • Gentamicin: Conventional dosing 2-2.5 mg/kg/dose IV q8h or once daily dosing 5-7.5 mg/kg/dose IV q24h 1

2. Alternative options (based on susceptibility):

   • Meropenem: For infants with gestational age <32 weeks and postnatal age <14 days: 20 mg/kg/dose IV q12h; for those with postnatal age ≥14 days: 20 mg/kg/dose IV q8h 1
   • Ceftazidime: 50 mg/kg/dose IV q8h or q12h (depending on gestational and postnatal age) 1

Rationale for Not Using Fosfomycin 1g in Infants

1. Lack of established dosing guidelines:

   • No formal dosing recommendations exist for fosfomycin in infants under 1 year 1
   • The 1g dose proposed is lower than the recommended dose even for older children (2-3g) 1

2. Limited efficacy data:

   • While fosfomycin shows good activity against E. coli (MIC90 ≤16 μg/ml), there is insufficient clinical evidence for its use in infants 2
   • Pharmacokinetic and pharmacodynamic data in infants are lacking

3. Safety concerns:

   • The safety profile of fosfomycin has not been well-established in infants under 1 year of age
   • Potential adverse effects and appropriate dosing in this age group remain uncertain

Special Considerations for MDR UTI in Infants

1. Parenteral therapy is preferred initially:

   • For serious infections with multidrug-resistant organisms in infants, parenteral therapy is the standard of care 1
   • The 2006 AAP guidelines state that fluoroquinolones (and by extension other oral options for MDR infections) may be justified only when "parenteral therapy is not feasible and no other effective oral agent is available" 1

2. Monitoring requirements:

   • Close monitoring of clinical response within 48-72 hours of starting treatment
   • Follow-up urine cultures to confirm clearance of infection
   • Evaluation for underlying urological abnormalities, which are more common in infants with UTI 1

Conclusion

For a 6-month-old infant with multidrug-resistant E. coli UTI, parenteral therapy with an aminoglycoside (amikacin or gentamicin) or a carbapenem (based on susceptibility testing) is the appropriate initial treatment. Fosfomycin at 1g oral dose is not recommended due to lack of established dosing guidelines, insufficient efficacy data, and potential safety concerns in this age group.