イミペネム・シラスタチンナトリウム
**イミペネム・シラスタチン**は、獣医学において重篤で生命を脅かす感染症や多剤耐性菌感染症のために予約されている、強力で広域スペクトルを持つ静脈内/筋肉内投与用の抗菌薬配合剤です。 * **イミペネム**は、グラム陽性菌、グラム陰性菌、および嫌気性菌を含む非常に広い抗菌スペクトルを持つカルバペネム系抗菌薬です。緑膿菌や腸内細菌科（ESBL産生菌など）のような耐性グラム陰性菌に対して特に有用です。 * **シラスタチン**はデヒドロペプチダーゼI（DHP I）阻害薬です。それ自体に抗菌活性はありませんが、腎臓の酵素によるイミペネムの急速な分解を防ぐため、非常に重要です。 > **臨床のポイント:** その広いスペクトルと高度耐性感染症治療における重要性から、イミペネムは「切り札」または予備の抗菌薬と見なされています。カルバペネム耐性菌の出現を防ぐため、理想的には培養および感受性試験に基づいて使用されるべきです。
作用機序: 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.
動物種別の用量
- 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.
投与経路
禁忌
- 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
有害事象
- 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)
薬物相互作用
- 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.
モニタリング
- 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
過量投与
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).
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。