Fosfomycin for Klebsiella pneumoniae UTI
Fosfomycin can be used to treat Klebsiella pneumoniae urinary tract infections, but has significantly lower efficacy against Klebsiella compared to E. coli, with susceptibility rates of only 36-58% for Klebsiella versus 95-96% for E. coli. 1, 2
Efficacy Against Klebsiella pneumoniae
- Fosfomycin shows variable susceptibility rates against Klebsiella pneumoniae, ranging from 36.5% to 57.6%, which is significantly lower than its effectiveness against E. coli (95-96%) 1, 2
- Klebsiella infections are more likely than E. coli to fail fosfomycin treatment and more likely to develop resistance following treatment 3
- In vitro studies demonstrate that fosfomycin's activity against Klebsiella is pH-dependent, with improved activity at acidic pH (pH 6.0) compared to neutral pH (pH 7.0) 4
Treatment Recommendations
- For uncomplicated UTIs, fosfomycin is FDA-approved for use against susceptible strains of Klebsiella pneumoniae, administered as a single 3-gram oral dose 5
- Before using fosfomycin for K. pneumoniae UTI, susceptibility testing should be performed to confirm activity, as resistance rates are significantly higher than with E. coli 2, 3
- For carbapenem-resistant K. pneumoniae (CRKP), fosfomycin susceptibility rates are variable (39-99%), and fosfomycin may be more effective when used in combination therapy with other agents 6
Considerations for Multidrug-Resistant Infections
- For multidrug-resistant K. pneumoniae, particularly ESBL-producing or carbapenem-resistant strains, fosfomycin may be a viable option when susceptibility is confirmed 2, 7
- Fosfomycin-containing combination therapies (with agents like tigecycline, polymyxin, or carbapenems) have shown potential benefit against carbapenem-resistant K. pneumoniae infections 6
- Observational studies suggest fosfomycin-containing combinations may reduce mortality in CRKP infections compared to other antimicrobial combinations, though evidence quality is very low 6
Clinical Pearls and Pitfalls
- The major pitfall is assuming similar efficacy against Klebsiella as against E. coli - always check susceptibility before treating K. pneumoniae with fosfomycin 2, 3
- Urine acidification may improve fosfomycin activity against K. pneumoniae, potentially enhancing clinical outcomes 4
- Fosfomycin has minimal propensity for collateral damage to intestinal flora, making it advantageous from an antibiotic stewardship perspective 6
- For complicated UTIs or pyelonephritis caused by K. pneumoniae, fosfomycin monotherapy is likely insufficient, and other agents or combination therapy should be considered 6
Alternative Options
- For uncomplicated UTIs, nitrofurantoin, trimethoprim-sulfamethoxazole, or fluoroquinolones may have better activity against K. pneumoniae than fosfomycin, depending on local susceptibility patterns 6, 2
- For multidrug-resistant K. pneumoniae, combination therapy including fosfomycin may be more effective than fosfomycin monotherapy 6