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).
กลไกการออกฤทธิ์: 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.
ขนาดยาตามชนิดสัตว์
- 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.
ขนาดยาเป็นข้อมูลอ้างอิงทางคลินิกสำหรับสัตวแพทย์ผู้มีใบอนุญาต โปรดตรวจสอบกับฉลากล่าสุดและผู้ป่วยแต่ละรายเสมอ
วิธีการให้ยา
ข้อห้ามใช้
- Young cats (Contraindicated due to nephrotoxicity)
- Adult cats (Relative contraindication; use with extreme caution if at all)
อาการไม่พึงประสงค์
- Diarrhea (most common in humans)
- Gastrointestinal upset
- Renal tubular damage / Nephrotoxicity (observed in cats)
อันตรกิริยาระหว่างยา
- 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.
การติดตาม
- 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
การได้รับยาเกินขนาด
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.
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