亞胺培南-西司他丁鈉
**亞胺培南-西司他丁 (Imipenem-cilastatin)** 是一種強效、廣效的靜脈/肌肉注射抗菌組合藥物，在獸醫學中保留用於治療嚴重、危及生命或多重抗藥性的感染。 * **亞胺培南 (Imipenem)** 是一種碳青黴烯類抗生素，具有極廣的抗菌譜，涵蓋革蘭氏陽性菌、革蘭氏陰性菌及厭氧菌。它對於具抗藥性的革蘭氏陰性菌（如綠膿桿菌和產ESBL的腸桿菌科）特別有價值。 * **西司他丁 (Cilastatin)** 是一種脫氫肽酶I (DHP I) 抑制劑。它本身沒有抗菌活性，但其作用至關重要，因為它可以防止亞胺培南在腎臟中被酵素快速降解。 > **臨床要點：** 由於其廣泛的抗菌譜和在治療高抗藥性感染中的重要性，亞胺培南被視為「最後防線」或儲備抗生素。理想情況下，應根據細菌培養和藥物敏感性試驗來指導其使用，以防止碳青黴烯類抗藥性細菌的出現。
作用機制: The drug functions through a synergistic two-part mechanism: 1. **Imipenem (Bactericidal Action):** Imipenem penetrates bacterial cell envelopes and binds with high affinity to **penicillin-binding proteins (PBPs)** (specifically PBP-2 and PBP-1B in gram-negative bacteria) → inhibits peptidoglycan cross-linking → disrupts bacterial cell wall synthesis → leads to cell lysis and death. 2. **Cilastatin (Pharmacokinetic Enhancer):** Imipenem is normally rapidly metabolized by **dehydropeptidase I (DHP I)**, an enzyme located on the brush borders of the proximal renal tubules. Cilastatin competitively inhibits **DHP I** → prevents imipenem degradation → ensures high, therapeutic antibacterial concentrations in the urine and protects the patient from proximal renal tubular necrosis that can occur if imipenem is administered alone.
各物種劑量
- Susceptible infections · 5-10 mg/kg · IV, SC or IM · q8h · IM form is different
- Susceptible infections · 5-10 mg/kg · IV or IM · q6h · IV given over 30 minutes. IM mixed with 1% lidocaine to reduce pain. Cannot interchange IV and IM dosage forms.
- Tissue infections · 3-7.5 mg/kg · IV, SC or IM · q4-6h · 3-5 days
- Sepsis, more resistant organisms · 5 mg/kg · IV · q4h · 3-5 days · Multi-drug resistant bacteria may require q2h dosing
- Treatment of Nocardiosis · 2-5 mg/kg · IV · q8h
- Susceptible infections (Adult horses) · 10-20 mg/kg · IV · q6h · Give via slow IV over a 10 minute period. Alternatively, a CRI of 16 micrograms/kg/minute should maintain synovial concentrations > 1 microgram/mL.
- Susceptible infections (Foals) · 10-20 mg/kg · IV · q6h
- Susceptible infections (Foals) · 10-15 mg/kg · IV or IM · q6-12h · IM if diluted into 1% lidocaine. May give as a CRI at 0.4-0.8 mg/kg/hr.
- Susceptible infections · 5-10 mg/kg · IV, SC or IM · q8h · IM form is different
- Susceptible infections · 5-10 mg/kg · IV or IM · q6h · IV given over 30 minutes. IM mixed with 1% lidocaine to reduce pain. Cannot interchange IV and IM dosage forms.
給藥途徑
禁忌症
- Patients with known hypersensitivity to imipenem, cilastatin, or other beta-lactam antibiotics (due to partial cross-reactivity)
- Caution in patients with renal impairment (dosage adjustment required)
- Caution in patients with underlying CNS disorders (e.g., seizures, head trauma) due to increased risk of neurotoxicity
不良反應
- Gastrointestinal upset (vomiting, anorexia, diarrhea)
- CNS toxicity (seizures, tremors)
- Hypersensitivity reactions (pruritus, fever, anaphylaxis)
- Infusion reactions (thrombophlebitis)
- Severe pain and potential neurovascular damage at IM injection sites
- Transient increases in BUN, serum creatinine, AST, ALT, and Alkaline Phosphatase
- Hypotension or tachycardia (rare)
藥物相互作用
- Aminoglycosides · Additive effects or synergy may result, particularly against Enterococcus, Staph. aureus, and Listeria monocytogenes. No synergy or antagonism noted against Enterobacteriaceae or Pseudomonas aeruginosa.
- Beta-Lactam Antibiotics · Antagonism may occur against several Enterobacteriaceae (including Pseudomonas aeruginosa, Klebsiella, Enterobacter, Serratia). Concurrent use is not recommended.
- Chloramphenicol · May antagonize the antibacterial effects of imipenem (based on in vitro evidence).
- Probenecid · May increase concentrations and elimination half-life of cilastatin, but not imipenem; concurrent use is not recommended.
- Trimethoprim/Sulfa · Synergy may occur against Nocardia asteroides when used in combination.
監測
- Clinical efficacy (resolution of infection signs)
- Adverse effects (especially CNS signs like tremors or seizures)
- Renal and hepatic function tests (BUN, creatinine, AST, ALT, Alk Phos) if treatment is prolonged or if the patient has pre-existing organ dysfunction
過量
Information on acute toxicity is limited. The LD50 of imipenem:cilastatin (1:1 ratio) in mice and rats is approximately 1 gram/kg/day. **Management:** * Halt therapy immediately. * Provide supportive and symptomatic care (e.g., anticonvulsants if seizures occur, fluid therapy to support renal clearance).
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