Fosfomycin for Klebsiella pneumoniae Infections
Fosfomycin can treat Klebsiella pneumoniae infections, but ONLY as part of combination therapy and ONLY when susceptibility testing confirms the isolate is susceptible (MIC ≤64 mcg/mL), particularly for carbapenem-resistant strains. 1, 2
Critical Prerequisite: Susceptibility Testing is Mandatory
- Fosfomycin susceptibility in K. pneumoniae is highly variable, ranging from 39% to 99%, making empiric use inappropriate. 1, 2
- You must confirm susceptibility through antimicrobial susceptibility testing before initiating therapy, and ideally perform synergy testing with the combination partner. 1, 2
- The FDA label confirms fosfomycin has in vitro activity against K. pneumoniae, but this does not guarantee clinical susceptibility in your specific isolate. 3
When to Use Fosfomycin for K. pneumoniae
Carbapenem-Resistant K. pneumoniae (CRKP)
- Fosfomycin-containing combination therapy is conditionally recommended for CRKP infections when susceptibility is confirmed. 1
- Use intravenous fosfomycin (2-4 g every 6 hours) in combination with tigecycline, polymyxin, carbapenems (at high doses with extended infusions), or aminoglycosides. 1, 4
- Fosfomycin combinations reduced mortality by 114 fewer deaths per 1000 patients with CRKP (RR 0.55), though evidence quality is very low. 1, 2
- Recent high-quality research from 2024 showed fosfomycin-containing regimens achieved 89.2% clinical cure versus 65.9% without fosfomycin (P=0.017), with significantly lower 30-day mortality (13.5% vs 34.2%, P=0.039). 5
Community-Acquired or Hospital-Acquired Infections
- For non-carbapenem-resistant K. pneumoniae, fosfomycin is NOT a first-line agent. 2
- Preferred alternatives include ceftazidime-avibactam for KPC-producing strains, or meropenem-vaborbactam. 2
Specific Clinical Scenarios
Urinary Tract Infections
- Aminoglycosides are superior to fosfomycin for complicated UTIs caused by carbapenem-resistant Enterobacterales. 2
- Oral fosfomycin tromethamine achieves urinary concentrations of 706 mcg/mL within 2-4 hours, maintaining levels ≥100 mcg/mL for 26 hours, but this formulation is indicated only for uncomplicated cystitis caused by susceptible organisms. 3
Bloodstream Infections and Sepsis
- Intravenous fosfomycin in combination therapy improved survival in sepsis caused by CRKP (OR 4.71,95% CI 1.03-21.65, P=0.034). 6
- All 11 critically ill ICU patients with CRKP infections treated with IV fosfomycin combinations achieved good bacteriological and clinical outcomes in a 2010 prospective study. 4
Absolute Contraindications and Monitoring
Avoid fosfomycin in patients with:
- Hypernatremia (due to high sodium content of IV formulation) 1, 2, 7
- Cardiac insufficiency 1, 2, 7
- Renal insufficiency 1
Monitor closely for:
- Hypokalemia (occurs in approximately 6% of ICU patients) 2, 7
- Serum potassium levels during therapy 7
Resistance Mechanisms and Pitfalls
- FosA-like genes are prevalent in CRKP and cause fosfomycin resistance. 1
- Carbapenemase-producing K. pneumoniae strains show higher fosfomycin resistance rates (40-45%) compared to carbapenemase-negative strains (20-25%). 8
- Never use fosfomycin as monotherapy for K. pneumoniae infections—resistance develops rapidly. 1, 5, 6, 4
Preferred Treatment Algorithm for CRKP
- First-line: Ceftazidime-avibactam for KPC-producing strains 2
- Second-line: Meropenem-vaborbactam or imipenem-cilastatin-relebactam 2
- For MBL-producing strains: Ceftazidime-avibactam PLUS aztreonam (strongly recommended) or cefiderocol 2
- Fosfomycin combinations: Reserve for cases where susceptibility is confirmed and preferred agents are unavailable or contraindicated 1, 2
Synergistic Combinations Supported by Evidence
- Fosfomycin plus amikacin shows persistent bactericidal effect and is highly effective. 9
- Fosfomycin plus imipenem, ertapenem, tigecycline, colistin, or amikacin all demonstrate significant additive effects in vitro. 9
- Fosfomycin with cephalosporins (like cefuroxime) can be safely co-administered without adverse pharmacodynamic interactions. 7