์ด๋ฏธํ๋ด-์ค๋ผ์คํํด ๋ํธ๋ฅจ
**์ด๋ฏธํ๋ด-์ค๋ผ์คํํด(Imipenem-cilastatin)**์ ์์ํ์์ ์ฌ๊ฐํ๊ณ ์๋ช ์ ์ํํ๊ฑฐ๋ ๋ค์ ๋ด์ฑ์ ๊ฐ์ง ๊ฐ์ผ์ ๋๋นํ์ฌ ๋ณด๋ฅ๋๋ ๊ฐ๋ ฅํ๊ณ ๊ด๋ฒ์ํ ์ ๋งฅ/๊ทผ์ก ์ฃผ์ฌ์ฉ ํญ๊ท ์ ๋ณตํฉ์ ์ ๋๋ค. * **์ด๋ฏธํ๋ด(Imipenem)**์ ๊ทธ๋ ์์ฑ๊ท , ๊ทธ๋ ์์ฑ๊ท ๋ฐ ํ๊ธฐ์ฑ ์ธ๊ท ์ ํฌํจํ์ฌ ๋งค์ฐ ๊ด๋ฒ์ํ ํ์ฑ ์คํํธ๋ผ์ ๊ฐ์ง ์นด๋ฐํ๋ด๊ณ ํญ์์ ์ ๋๋ค. ๋ น๋๊ท (Pseudomonas aeruginosa) ๋ฐ ์ฅ๋ด์ธ๊ท ๊ณผ(์: ESBL ์์ฑ ๊ท ์ฃผ)์ ๊ฐ์ ๋ด์ฑ ๊ทธ๋ ์์ฑ๊ท ์ ํนํ ์ ์ฉํฉ๋๋ค. * **์ค๋ผ์คํํด(Cilastatin)**์ ๋ํ๋๋กํฉํฐ๋ค์์ I (DHP I) ์ต์ ์ ์ ๋๋ค. ์์ฒด์ ์ธ ํญ๊ท ํ์ฑ์ ์์ง๋ง, ์ ์ฅ์ ํจ์์ ์ํด ์ด๋ฏธํ๋ด์ด ๋น ๋ฅด๊ฒ ๋ถํด๋๋ ๊ฒ์ ๋ฐฉ์งํ๊ธฐ ๋๋ฌธ์ ๋งค์ฐ ์ค์ํฉ๋๋ค. > **์์ ์์ :** ๊ด๋ฒ์ํ ์คํํธ๋ผ๊ณผ ๊ณ ๋ ๋ด์ฑ ๊ฐ์ผ ์น๋ฃ์์์ ์ค์์ฑ ๋๋ฌธ์ ์ด๋ฏธํ๋ด์ "์ตํ์ ๋ณด๋ฃจ" ๋๋ ์๋น ํญ์์ ๋ก ๊ฐ์ฃผ๋ฉ๋๋ค. ์นด๋ฐํ๋ด ๋ด์ฑ๊ท ์ ์ถํ์ ๋ฐฉ์งํ๊ธฐ ์ํด ์ด์์ ์ผ๋ก๋ ๋ฐฐ์ ๋ฐ ๊ฐ์์ฑ ๊ฒ์ฌ๋ฅผ ๋ฐํ์ผ๋ก ์ฌ์ฉํด์ผ ํฉ๋๋ค.
์์ฉ ๊ธฐ์ : 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) โ inhibits peptidoglycan cross-linking โ disrupts bacterial cell wall synthesis โ 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** โ prevents imipenem degradation โ 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.
๋๋ฌผ ์ข ๋ณ ์ฉ๋
- Susceptible infections ยท 5-10 mg/kg ยท IV, SC or IM ยท q8h ยท IM form is different
- Susceptible infections ยท 5-10 mg/kg ยท IV or IM ยท q6h ยท IV given over 30 minutes. IM mixed with 1% lidocaine to reduce pain. Cannot interchange IV and IM dosage forms.
- Tissue infections ยท 3-7.5 mg/kg ยท IV, SC or IM ยท q4-6h ยท 3-5 days
- Sepsis, more resistant organisms ยท 5 mg/kg ยท IV ยท q4h ยท 3-5 days ยท Multi-drug resistant bacteria may require q2h dosing
- Treatment of Nocardiosis ยท 2-5 mg/kg ยท IV ยท q8h
- Susceptible infections (Adult horses) ยท 10-20 mg/kg ยท IV ยท q6h ยท 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) ยท 10-20 mg/kg ยท IV ยท q6h
- Susceptible infections (Foals) ยท 10-15 mg/kg ยท IV or IM ยท q6-12h ยท IM if diluted into 1% lidocaine. May give as a CRI at 0.4-0.8 mg/kg/hr.
- Susceptible infections ยท 5-10 mg/kg ยท IV, SC or IM ยท q8h ยท IM form is different
- Susceptible infections ยท 5-10 mg/kg ยท IV or IM ยท q6h ยท IV given over 30 minutes. IM mixed with 1% lidocaine to reduce pain. Cannot interchange IV and IM dosage forms.
ํฌ์ฌ ๊ฒฝ๋ก
๊ธ๊ธฐ
- 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
์ด์๋ฐ์
- 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)
์ฝ๋ฌผ ์ํธ์์ฉ
- Aminoglycosides ยท 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 ยท Antagonism may occur against several Enterobacteriaceae (including Pseudomonas aeruginosa, Klebsiella, Enterobacter, Serratia). Concurrent use is not recommended.
- Chloramphenicol ยท May antagonize the antibacterial effects of imipenem (based on in vitro evidence).
- Probenecid ยท May increase concentrations and elimination half-life of cilastatin, but not imipenem; concurrent use is not recommended.
- Trimethoprim/Sulfa ยท Synergy may occur against Nocardia asteroides when used in combination.
๋ชจ๋ํฐ๋ง
- 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
๊ณผ์ฉ๋
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 ์ฝ๋ฌผ ๋ ํผ๋ฐ์ค๋ ๋ฉดํ ์์ ์ ๋ฌธ๊ฐ๋ฅผ ์ํ ์์ ์์ฌ๊ฒฐ์ ๋ณด์กฐ ๋๊ตฌ์ด๋ฉฐ, ์ ๋ฌธ์ ํ๋จ์ด๋ ์ ์กฐ์ฌ์ ์ต์ ๋ผ๋ฒจ์ ๋์ ํ์ง ์์ต๋๋ค.