Fosfomycin for Klebsiella UTI

Key Considerations

• Fosfomycin is not recommended as monotherapy for Klebsiella pneumoniae UTI due to poor susceptibility, but may be considered for carbapenem-resistant strains in combination therapy when susceptibility is confirmed, as per the Journal of Microbiology, Immunology and Infection 1

When Fosfomycin May Be Considered

• Fosfomycin-containing combination therapy may be used for CRKP UTI only when susceptibility testing confirms the isolate is susceptible to fosfomycin, with combination partners including tigecycline, polymyxin, or carbapenems based on synergy testing results 1, 2
• Fosfomycin susceptibility in CRKP is highly variable, making susceptibility testing mandatory before use 1, 2

Critical Contraindications

• Fosfomycin should be avoided in patients with hypernatremia, cardiac insufficiency, or renal insufficiency due to the high sodium content of the formulation 1, 2

Preferred Alternatives for Klebsiella UTI

• Single-dose aminoglycoside is preferred for simple cystitis caused by carbapenem-resistant Klebsiella 3
• Ceftazidime-avibactam is the preferred agent for carbapenem-resistant Klebsiella in complicated UTI or pyelonephritis 3
• Meropenem-vaborbactam or imipenem-cilastatin-relebactam are alternative options for complicated UTI or pyelonephritis 3
• Plazomicin is recommended for complicated UTI due to carbapenem-resistant Klebsiella 3

Clinical Pitfalls

• If fosfomycin is used for CRKP, it must be intravenous formulation in combination therapy, not the oral single-dose formulation 1, 2

Fosfomycin Treatment for Complicated UTI

Intravenous Fosfomycin Recommendations

• The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines recommend IV fosfomycin for complicated UTI without septic shock based on the ZEUS trial 4

Combination Therapy Requirements

• The American College of Clinical Pharmacy and other guideline societies imply that fosfomycin should be used in combination therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP) when susceptibility is confirmed, although no specific guideline is cited here, the general principle is supported by various medical organizations 4

Fosfomycin Use in Stage 3 CKD

Contraindications and Precautions

• Fosfomycin should be avoided in stage 3 CKD patients with hypernatremia, cardiac insufficiency, or concurrent severe renal insufficiency approaching stage 4-5 CKD, as recommended by the Journal of Microbiology, Immunology and Infection 5

Treatment Guidance

• For carbapenem-resistant organisms in stage 3 CKD, IV fosfomycin-containing combination therapy may be used when susceptibility testing confirms the isolate is susceptible to fosfomycin, used in combination, and patient does not have hypernatremia or cardiac insufficiency, as recommended by the Journal of Microbiology, Immunology and Infection 5