Is fosfomycin (an antibiotic) effective against Klebsiella pneumoniae infections in adult patients with normal renal function?

Does Fosfomycin Cover Klebsiella pneumoniae?

Fosfomycin has variable activity against Klebsiella pneumoniae and should NOT be used as monotherapy, but may be considered as part of combination therapy for carbapenem-resistant strains only when susceptibility testing confirms the isolate is susceptible. 1

Susceptibility Patterns

Fosfomycin susceptibility in K. pneumoniae is highly inconsistent and depends on resistance mechanisms:

• Carbapenem-resistant K. pneumoniae (CRKP): Susceptibility rates range from 39% to 99%, making susceptibility testing mandatory before use 2
• KPC-producing strains: Approximately 65% susceptible based on reference methods, though carbapenemase-producing strains show higher resistance (45% resistant) compared to carbapenemase-negative strains (25% resistant) 3
• Resistance mechanisms: The mobile resistance gene fosA3 is prevalent (36.3% of KPC-producing strains in China), and glpT gene mutations further compromise activity 4

When Fosfomycin May Be Used

Fosfomycin-containing combination therapy is conditionally recommended for carbapenem-resistant K. pneumoniae infections ONLY when:

1. Susceptibility is confirmed through antimicrobial susceptibility testing (MIC ≤64 mcg/mL) 2, 5
2. Synergy testing demonstrates benefit with the combination partner 2
3. Intravenous formulation is used (not oral single-dose) in combination with tigecycline, polymyxin, or carbapenems 2, 1

Evidence for Combination Therapy

• Fosfomycin-containing combinations reduced mortality by 114 fewer deaths per 1000 patients with CRKP infections (RR 0.55,95% CI 0.28-1.10), though evidence quality is very low 2
• In critically ill ICU patients with KPC-producing K. pneumoniae, fosfomycin combinations 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) 6
• Time-kill assays demonstrate fosfomycin enhances bactericidal activity when combined with imipenem, ertapenem, tigecycline, colistin, or amikacin against KPC-producing strains 7

Critical Contraindications

Avoid fosfomycin in patients with: 2, 8, 1

• Hypernatremia (high sodium content of formulation)
• Cardiac insufficiency
• Renal insufficiency
• Monitor serum potassium closely—hypokalemia occurs in approximately 6% of ICU patients 8

Preferred Alternatives for K. pneumoniae Infections

For carbapenem-resistant K. pneumoniae, prioritize these evidence-based options over fosfomycin: 1

• Ceftazidime-avibactam: Preferred first-line agent for KPC-producing strains
• Meropenem-vaborbactam or imipenem-cilastatin-relebactam: Alternative β-lactam/β-lactamase inhibitor combinations
• Ceftazidime-avibactam PLUS aztreonam: Strong recommendation for metallo-β-lactamase (MBL)-producing strains 2
• Cefiderocol: Conditional recommendation for MBL-producing strains 2
• Plazomicin: Recommended for complicated UTI
• Single-dose aminoglycoside: Preferred for simple cystitis

Common Pitfalls

• Never use oral fosfomycin for systemic K. pneumoniae infections—the oral formulation achieves therapeutic concentrations only in urine, not in blood or tissues 1, 5
• Do not assume susceptibility—resistance rates are too variable (35-61% resistant in some cohorts) to use empirically 3, 4
• Monotherapy fails frequently—fosfomycin monotherapy leads to rapid emergence of resistance within 48 hours 7, 9
• Aminoglycosides are superior for urinary tract infections—fosfomycin showed inferior outcomes compared to aminoglycoside-containing regimens for cUTI caused by carbapenem-resistant Enterobacterales 2