磷黴素氨丁三醇
磷黴素是一種獨特的合成廣效**膦酸衍生物抗生素**。最初從弗氏鏈黴菌 (*Streptomyces fradiae*) 中分離出來，在人類醫學中主要作為單劑量療法用於治療單純性泌尿道感染 (UTI)。 在獸醫學中，其使用仍處於高度試驗階段，但作為以下情況的「救援」或後備抗菌藥物正受到關注： - **多重抗藥性 (MDR) 大腸桿菌 (*Escherichia coli*)** - **產生廣效性乙內醯胺酶 (ESBL) 的腸桿菌科細菌** - 難治性腸球菌感染 **臨床要點：** - 它主要是一種**時間依賴性**殺菌劑，但也表現出一些濃度依賴性特徵。 - 通常不會與乙內醯胺類或氨基醣苷類藥物產生交叉抗藥性，這使其在標準第一線抗生素失效時成為有價值的選擇。 - **重要提示：** 美國市售的口服製劑為*氨丁三醇 (tromethamine)* 鹽，而許多獸醫藥代動力學研究使用的是*二鈉 (disodium)* 鹽（用於腸胃外給藥）。
作用機制: 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.
各物種劑量
- 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.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Young cats (Contraindicated due to nephrotoxicity)
- Adult cats (Relative contraindication; use with extreme caution if at all)
不良反應
- Diarrhea (most common in humans)
- Gastrointestinal upset
- Renal tubular damage / Nephrotoxicity (observed in cats)
藥物相互作用
- 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.
監測
- 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
過量
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.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。