Fosfomycin for Klebsiella pneumoniae UTI
Fosfomycin is NOT recommended as monotherapy for Klebsiella pneumoniae UTI due to poor susceptibility (only 36-62% susceptible), but may be considered as part of combination therapy for carbapenem-resistant strains when susceptibility testing confirms the isolate is susceptible. 1, 2
Key Susceptibility Data
- Klebsiella pneumoniae shows poor susceptibility to fosfomycin with MIC90 >512 μg/ml, making it ineffective as monotherapy 3
- Fosfomycin susceptibility rates for K. pneumoniae are only 38.1% for non-ESBL strains and 36.5% for ESBL-producing strains 4
- In contrast, E. coli demonstrates 95-96% susceptibility to fosfomycin, highlighting the organism-specific limitations 4
- ESBL-producing Klebsiella isolates show only 61.7% susceptibility to fosfomycin, significantly lower than ESBL E. coli at 94.9% 5
When Fosfomycin May Be Used for Klebsiella UTI
For carbapenem-resistant K. pneumoniae (CRKP) only:
- Fosfomycin-containing combination therapy may be used when susceptibility testing confirms the isolate is susceptible 1, 2
- Combination partners should include tigecycline, polymyxin, or carbapenems based on synergy testing results 1
- Intravenous fosfomycin formulation must be used in combination therapy, NOT the oral single-dose formulation 1
- Polymyxin B plus fosfomycin (6g IV q6h as 1-hour infusion) demonstrated sustained bactericidal activity against KPC-producing K. pneumoniae in pharmacodynamic studies 6
Preferred Treatment Options for Klebsiella UTI
For carbapenem-resistant Klebsiella:
- Ceftazidime-avibactam is the preferred agent for complicated UTI or pyelonephritis caused by carbapenem-resistant Klebsiella 1
- Meropenem-vaborbactam is recommended as a treatment option for CRE-UTI 7
- Imipenem-cilastatin-relebactam is recommended as a treatment option for CRE-UTI 7
- Plazomicin is recommended for complicated UTI due to carbapenem-resistant Klebsiella 7, 1
- Single-dose aminoglycoside is preferred for simple cystitis caused by carbapenem-resistant Klebsiella 1
For carbapenem-susceptible Klebsiella:
- Carbapenems (imipenem, meropenem) remain the most effective agents with near-universal susceptibility 5
- Amikacin shows 94.1% susceptibility against ESBL-producing Klebsiella in healthcare-associated UTI 5
Critical Contraindications and Safety Concerns
- Fosfomycin should be avoided in patients with hypernatremia, cardiac insufficiency, or renal insufficiency due to the high sodium content of the formulation 1
- In anuric patients undergoing hemodialysis, the half-life of fosfomycin increases to 40 hours 8
- In patients with renal impairment (creatinine clearance 7-54 mL/min), the half-life increases from 11 to 50 hours with decreased urinary recovery from 32% to 11% 8
Clinical Pitfalls to Avoid
- Do not use oral fosfomycin tromethamine (single 3g dose) for Klebsiella UTI - this formulation is FDA-approved only for uncomplicated cystitis in women caused by susceptible organisms, primarily E. coli and Enterococcus faecalis 8
- The oral formulation achieves urinary concentrations of 706 mcg/mL within 2-4 hours, but this is insufficient for most Klebsiella strains with MIC90 >512 μg/ml 8, 3
- Mandatory susceptibility testing before using fosfomycin for Klebsiella - susceptibility is highly variable (39-99%) and cannot be assumed 1, 2
- Fosfomycin monotherapy selects for resistance by 24 hours in KPC-producing K. pneumoniae 6
- Most fosfomycin-resistant Klebsiella isolates remain susceptible to other first-line agents, making alternative antibiotics more appropriate 4
Treatment Algorithm for Klebsiella UTI
Step 1: Obtain urine culture with susceptibility testing
Step 2: Classify infection severity
- Simple cystitis → Single-dose aminoglycoside for CRKP 1
- Complicated UTI/pyelonephritis → Proceed to Step 3
Step 3: Determine carbapenem resistance status
- Carbapenem-susceptible → Use carbapenem (meropenem, ertapenem) 5
- Carbapenem-resistant → Proceed to Step 4
Step 4: For CRKP, select based on susceptibility: