妥布黴素
妥布黴素是一種強效的非腸道給藥**氨基醣苷類抗生素**，主要用於治療嚴重的革蘭氏陰性需氧菌感染。 **主要臨床特徵：** * **抗菌譜：** 對需氧革蘭氏陰性桿菌（如綠膿桿菌、大腸桿菌、克雷伯氏菌、變形桿菌）及部分需氧革蘭氏陽性菌（如葡萄球菌）高度有效。對厭氧菌和真菌無效。 * **臨床應用：** 由於其固有的毒性，全身性使用通常保留用於其他毒性較低的抗生素無效的嚴重、危及生命的感染，或用於治療已知的抗慶大黴素菌株。 * **毒性特徵：** 與所有氨基醣苷類藥物一樣，具有顯著的**腎毒性**和**耳毒性**風險。部分實驗室證據表明其腎毒性可能略低於慶大黴素，但臨床上仍有爭議。 > **臨床要點：** 氨基醣苷類藥物表現出**濃度依賴性殺菌活性**和顯著的**抗生素後效應 (PAE)**。這種藥代動力學/藥效學特徵強烈支持現代的高劑量、延長間隔（每日一次）給藥方案。這種方法最大化了用於殺菌的 $C_{max}$/MIC 比值，同時提供了一個無藥物間隔期，使腎小管細胞能夠清除藥物，從而將腎毒性降至最低。
作用機制: Tobramycin is a **bactericidal** antibiotic that disrupts bacterial protein synthesis. * **Cellular Entry:** The drug enters the bacterial cell via an **oxygen-dependent active transport mechanism**. > **Note:** Because this transport requires oxygen, aminoglycosides are completely ineffective against obligate anaerobic bacteria and have reduced efficacy in anaerobic environments (e.g., abscesses, necrotic tissue). * **Target Binding:** Once inside, tobramycin irreversibly binds to the **30S ribosomal subunit**. * **Mechanism:** Binding → misreading of mRNA → incorporation of incorrect amino acids into the growing peptide chain → production of non-functional or toxic proteins → bacterial cell death. * **Environmental Factors:** Antimicrobial activity is significantly enhanced in an **alkaline environment** and diminished in acidic, purulent conditions.
各物種劑量
- General susceptible infections · 2 mg/kg · IV, IM, SC · q8h · Consider consolidating to once-daily dosing.
- Susceptible UTI · 1-2 mg/kg · SC · q8h
- Sepsis · 2-4 mg/kg · IV · q8h
- Soft tissue, systemic infections · 2 mg/kg IV, IM or SC q12h or 4 mg/kg IV, IM, SC q24h · IV, IM, SC · q12h or q24h · <= 5 days
- Persistent bacteremia · 2 mg/kg IV, IM, SC q8h or 6 mg/kg IV, IM or SC q24h · IV, IM, SC · q8h or q24h · <= 5 days
- Gram-negative infections · 4-6 mg/kg · IV/IM/SC · q24h · Assess according to clinical response · Cats may be more sensitive to toxicity. For severe infections (including sepsis), doses as high as 12 mg/kg/day have been advocated, but should be used with caution.
- Susceptible infections · 4 mg/kg · IV · q24h · Allows achievement of Cmax/MIC ratio higher than 10 for pathogen strains with a MIC of 1 microgram/mL.
- Susceptible infections · 5 mg/kg · IM · q12h
- Susceptible infections · 2.5-5 mg/kg/day · Parenteral · Daily
給藥途徑
禁忌症
- Known hypersensitivity to aminoglycosides
- Rabbits and hares (causes fatal disruption of GI flora)
- Pre-existing severe renal disease (unless benefits outweigh risks)
- Dehydration
- Corneal ulceration (specifically for ophthalmic preparations)
不良反應
- Nephrotoxicity (acute tubular necrosis)
- Ototoxicity (vestibular and auditory damage, potentially irreversible)
- Neuromuscular blockade
- Facial edema
- Pain or inflammation at the injection site
- Peripheral neuropathy
- Hypersensitivity reactions
- Rarely: GI signs, hematologic, and hepatic effects
- Ototoxicity (vestibular and auditory damage)
- Neuromuscular blockade (rare)
藥物相互作用
- Beta-lactam antibiotics (penicillins, cephalosporins) · Synergistic antibacterial effects in vivo; however, can cause physical inactivation of aminoglycosides if mixed in the same syringe or IV line, or in vivo in patients with severe renal failure. · moderate
- Cephalosporins · Potential for additive nephrotoxicity (historically documented with older generation cephalosporins like cephalothin).
- Loop Diuretics (furosemide, torsemide) · Increased risk of nephrotoxicity and ototoxicity.
- Osmotic Diuretics (mannitol) · Increased risk of nephrotoxicity and ototoxicity.
- Other Nephrotoxic Drugs (cisplatin, amphotericin B, polymyxin B, vancomycin) · Significantly increased risk of acute kidney injury.
- Neuromuscular Blocking Agents & General Anesthetics · Concomitant use can potentiate and prolong neuromuscular blockade, potentially leading to respiratory paralysis.
- Amphotericin B · Increased risk of nephrotoxicity · major
- Furosemide · Increased risk of ototoxicity and nephrotoxicity · major
- Heparin · In vitro chemical inactivation if mixed · minor
- Pancuronium · Enhanced non-depolarizing neuromuscular blockade · moderate
監測
- Clinical efficacy (resolution of fever, improved clinical signs, negative follow-up cultures)
- Renal toxicity: Baseline and serial urinalysis (monitoring for tubular casts, which are often the first sign of impending toxicity), urine specific gravity, serum creatinine, and BUN
- Gross monitoring for vestibular toxicity (head tilt, nystagmus, ataxia) or auditory toxicity (deafness)
- Therapeutic drug monitoring (peak and trough serum levels) is highly recommended to ensure efficacy and prevent toxicity
- Urinalysis (daily, looking for cellular casts as an early warning)
- Serum creatinine and BUN (baseline and periodically)
- Hydration status and urine output
- Auditory and vestibular function
過量
In the event of an inadvertent overdose, rapid intervention is required to prevent permanent renal and otic damage: * **Hemodialysis:** Highly effective in reducing serum levels of the drug, though rarely available in veterinary practice. * **Peritoneal Dialysis:** Can reduce serum levels but is significantly less efficacious than hemodialysis. * **Drug Complexation:** Intravenous administration of carbenicillin or ticarcillin (12-20 grams/day in humans) can complex with tobramycin in the blood, inactivating it. This is reportedly nearly as effective as hemodialysis.
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