Fosfomycin for Klebsiella UTI
Fosfomycin is NOT recommended as monotherapy for Klebsiella pneumoniae UTI due to poor susceptibility (only 36-38% of isolates are susceptible), but may be considered for carbapenem-resistant strains in combination therapy when susceptibility is confirmed. 1, 2
Key Limitations of Fosfomycin for Klebsiella
The FDA label explicitly approves fosfomycin only for E. coli and Enterococcus faecalis UTIs—Klebsiella is NOT an FDA-approved indication. 2
Fosfomycin demonstrates poor activity against Klebsiella species with MIC90 values >512 μg/ml, compared to excellent activity against E. coli (MIC90 ≤16 μg/ml). 3
Resistance rates are dramatically higher in Klebsiella (19%) versus E. coli (1%), and Klebsiella infections are significantly more likely to fail fosfomycin treatment. 4
Pharmacodynamic modeling shows only 55% probability of achieving target drug exposure against Klebsiella species, compared to 99% for E. coli. 3
When Fosfomycin May Be Considered
For Carbapenem-Resistant Klebsiella pneumoniae (CRKP)
Fosfomycin-containing combination therapy (NOT monotherapy) may be used for CRKP UTI only when susceptibility testing confirms the isolate is susceptible to fosfomycin. 1
Combination partners should include tigecycline, polymyxin, or carbapenems based on synergy testing results. 1
Fosfomycin susceptibility in CRKP is highly variable (39-99%), making susceptibility testing mandatory before use. 1
Critical Contraindications
- Avoid fosfomycin in patients with hypernatremia, cardiac insufficiency, or renal insufficiency due to the high sodium content of the formulation. 1
Preferred Alternatives for Klebsiella UTI
For Uncomplicated Cystitis
- Single-dose aminoglycoside (gentamicin or amikacin) is preferred for simple cystitis caused by carbapenem-resistant Klebsiella. 1
For Complicated UTI or Pyelonephritis
- Ceftazidime-avibactam 2.5g IV q8h is the preferred agent for carbapenem-resistant Klebsiella. 1
- Meropenem-vaborbactam 4g IV q8h or imipenem-cilastatin-relebactam 1.25g IV q6h are alternative options. 1
- Plazomicin 15 mg/kg IV q12h is recommended for complicated UTI due to carbapenem-resistant Klebsiella. 1
Clinical Pitfalls
Do not use oral fosfomycin monotherapy for Klebsiella UTI—treatment failure rates are unacceptably high, and this is an off-label use. 2, 4
If fosfomycin is used for CRKP, it must be intravenous formulation in combination therapy, not the oral single-dose formulation. 1
Urine acidification (pH 6.0) can improve fosfomycin activity against Klebsiella, but even with acidification, only 55% of isolates achieve adequate drug exposure. 3
If bacteriuria persists or recurs after any fosfomycin treatment attempt, switch to alternative agents immediately rather than repeating fosfomycin. 2