Fosfomycin Treatment Course for Multi-Drug Resistant (MDR) Infections
For MDR infections, fosfomycin dosing varies by infection type, with a single 3g oral dose recommended for uncomplicated UTIs caused by VRE, while more severe MDR infections typically require IV formulations at doses of 12-24g/day divided into multiple doses.
Recommended Fosfomycin Regimens by Infection Type
Uncomplicated Urinary Tract Infections
- For uncomplicated UTIs caused by vancomycin-resistant enterococci (VRE), a single 3g oral dose of fosfomycin is recommended (weak recommendation, very low quality of evidence) 1
- Alternatively, fosfomycin 3g PO every other day may be used for VRE UTIs 1
- Treatment duration for uncomplicated UTIs should be 3-7 days 1
Complicated UTIs and Systemic Infections
- For complicated UTIs caused by carbapenem-resistant Enterobacterales (CRE), IV formulations are preferred over oral 1
- For severe MDR infections, IV fosfomycin doses typically range between 12-24g/day divided into multiple doses 2
- For patients with normal kidney function (CrCl 91-120 mL/min), a total daily dose of 15g/day is suggested 3
- Dosing intervals of 6-8 hours are preferred over 12-hour intervals for optimal time above MIC (except in premature neonates) 4
Considerations for Specific MDR Pathogens
Efficacy Against Different Organisms
- Fosfomycin shows excellent activity against MDR E. coli, including ESBL-producing strains, with resistance rates as low as 1% 5
- Fosfomycin is less effective against Klebsiella species, with resistance rates of approximately 19% 5
- For VRE infections, fosfomycin is a viable alternative when other options are limited 1
Combination Therapy
- For severe infections caused by CRE resistant to newer antibiotics, fosfomycin is often used in combination with other agents 1
- Fosfomycin has demonstrated synergistic in vitro activity against carbapenem-resistant Klebsiella pneumoniae (CRKP) when combined with other antibiotics 1
- Monotherapy is not recommended for severe MDR infections outside of uncomplicated UTIs 1
Dosage Adjustments
Renal Function
- Dose adjustment is required based on creatinine clearance 3
- For patients with impaired kidney function, lower doses should be used to avoid dose-limiting side effects 3
Age-Based Considerations
- In pediatric patients, dosing is primarily based on bodyweight and age 4
- For neonates with postmenstrual age <40 weeks, lower doses of 100 mg/kg/day may be considered 4
Monitoring and Safety
Therapeutic Drug Monitoring (TDM)
- TDM should be performed when possible, especially for prolonged courses or in patients with renal impairment 1
- The pharmacokinetic/pharmacodynamic parameter most predictive of success is the time above MIC (T>MIC) 4
Common Pitfalls to Avoid
- Underestimating required doses for MDR infections with higher MICs (≥32 mg/L), especially in patients with normal renal function 4
- Using oral formulations for pyelonephritis or perinephric abscess, which is not recommended 1
- Relying on fosfomycin monotherapy for severe systemic infections, which has limited evidence 1
- Failing to adjust dosing based on renal function, which can lead to toxicity 3
Duration of Therapy
- For uncomplicated UTIs: 3-7 days 1
- For complicated UTIs: 5-7 days 1
- For bloodstream infections: 7-14 days 1
- Treatment duration should be individualized according to infection site, source control, underlying comorbidities, and initial response to therapy 1
In conclusion, fosfomycin represents an important treatment option for MDR infections, particularly for UTIs caused by resistant organisms. The dosing regimen must be carefully selected based on the infection site, pathogen, and patient characteristics, with particular attention to renal function.