Fosfomycin
Fosfomycin is a unique, synthetic, broad-spectrum **phosphonic acid derivative antibiotic**. Originally isolated from *Streptomyces fradiae*, it is primarily utilized in human medicine as a single-dose treatment for uncomplicated urinary tract infections (UTIs). In veterinary medicine, its use is highly investigational but gaining attention as a "rescue" or reserve antimicrobial for: - **Multi-drug resistant (MDR) *Escherichia coli*** - **Extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae** - Refractory *Enterococcus* infections **Clinical Pearls:** - It is primarily a **time-dependent** bactericidal agent, though it exhibits some concentration-dependent characteristics. - Cross-resistance with beta-lactams or aminoglycosides does not typically occur, making it a valuable option when standard first-line antibiotics fail. - **Important:** The oral formulation available in the US is the *tromethamine* salt, while many veterinary pharmacokinetic studies have utilized the *disodium* salt (which is administered parenterally).
Mecanismo: Fosfomycin exerts its bactericidal effect by interfering with the very first step of bacterial cell wall (peptidoglycan) synthesis. - It acts as a structural analogue of phosphoenolpyruvate (PEP). - It irreversibly binds to and inhibits the cytosolic enzyme **MurA (UDP-N-acetylglucosamine enolpyruvyl transferase)**. - **Pathway:** Blocks addition of PEP to UDP-N-acetylglucosamine → Prevents formation of **uridine diphosphate-N-acetylmuramic acid (UDP-MurNAc)** → Halts peptidoglycan synthesis → Bacterial cell lysis. - **Secondary Action:** It also reduces the adherence of bacteria to uroepithelial cells, which is highly beneficial in treating UTIs. - **Resistance Mechanism:** When resistance occurs, it is typically chromosomally mediated via the production of **FosA** or **FosX** enzymes, which hydrolyze and inactivate the drug.
Dosificación por especie
- Susceptible infections (Investigational) · 20 mg/kg · SC · q10h · Unknown · Based on PK study using fosfomycin disodium (not commercially available in USA). May maintain effective plasma concentrations for up to 10 hours.
- Urinary Tract Infection (MDR E. coli) · 40 mg/kg · PO · Single dose · Single dose · Investigational. Dose based on disodium salt in a PK study. Use should be prudently reserved for MDR E. coli based on susceptibility testing only when no other alternative exists.
Las dosis son una referencia clínica para médicos veterinarios. Confirme siempre con la información vigente del producto y el paciente individual.
Vías de administración
Contraindicaciones
- Young cats (Contraindicated due to nephrotoxicity)
- Adult cats (Relative contraindication; use with extreme caution if at all)
Efectos adversos
- Diarrhea (most common in humans)
- Gastrointestinal upset
- Renal tubular damage / Nephrotoxicity (observed in cats)
Interacciones farmacológicas
- Metoclopramide · Can decrease serum concentrations and reduce urine levels of fosfomycin.
- Prokinetic agents (bethanechol, cisapride, domperidone, ranitidine, laxatives) · Theoretical risk of decreasing serum and urine concentrations by increasing GI motility, similar to metoclopramide.
Monitoreo
- Gastrointestinal adverse effects (diarrhea)
- Clinical signs of UTI resolution
- Urine culture and susceptibility (pre- and post-treatment)
- Urinalysis
- Renal function tests (BUN, Creatinine) especially if used off-label in cats
Sobredosis
Single overdoses are most likely to cause **gastrointestinal effects** (e.g., severe diarrhea). In cats, overdosage or even standard doses can cause severe **nephrotoxicity** (tubular necrosis). Treatment should be supportive and symptomatic.
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.