作用機序: Amikacin actively transports across the bacterial cell membrane via an **oxygen-dependent mechanism** (which is why it is ineffective against anaerobic bacteria). Once inside, it binds irreversibly to the **30S ribosomal subunit**.
Binding to 30S subunit → interferes with the initiation complex between mRNA and the ribosome → causes misreading of the genetic code → produces nonfunctional proteins → leads to rapid bacterial cell death.
**Clinical Pearl:** Its antimicrobial activity is significantly enhanced in an alkaline environment and markedly reduced in purulent, acidic, or necrotic debris.
動物種別の用量
Cats
Empiric therapy · 10-15 mg/kg · IV/IM/SC · Not specified · Route not specified, assume IV, IM or SC
Susceptible infections · 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). · Not specified · q24h (or q8h)
Sepsis · 20 mg/kg once daily IV · IV · q24h
Ferrets
Susceptible infections · 8-16 mg/kg IM or IV once daily · IM/IV · q24h
Susceptible infections · 10 mg/kg IM q8h or 25 mg/kg q12h · IM · q8h or q12h
Susceptible infections · 22 mg/kg/day IM divided three times daily · IM · TID
Horses
Susceptible infections · 21 mg/kg IV or IM once daily (q24h) · IV/IM · q24h
Susceptible infections (Neonatal foals) · 21 mg/kg IV once daily · IV · q24h
Susceptible infections (Neonatal foals) · Initial dose of 25 mg/kg IV once daily · IV · q24h · Strongly recommend to individualize dosage based upon therapeutic drug monitoring.
Generally contraindicated in rabbits/hares (adversely affects GI flora balance)
有害事象
Nephrotoxicity (tubular necrosis)
Ototoxicity (auditory and vestibular)
Neuromuscular blockade
Facial edema
Injection site pain/inflammation
Peripheral neuropathy
Hypersensitivity reactions
薬物相互作用
Beta-lactam antibiotics (penicillins, cephalosporins) · May have synergistic effects against some bacteria; potential for physical inactivation of aminoglycosides in vitro (do not mix together) and in vivo (patients in renal failure).
Cephalosporins · Potentially could cause additive nephrotoxicity (controversial, well documented only with older agents like cephaloridine and cephalothin).
Loop or Osmotic Diuretics (e.g., furosemide, torsemide, mannitol) · Concurrent use may increase the nephrotoxic or ototoxic potential of the aminoglycosides.
NSAIDs · May cause nephrotoxic effects; concurrent use with aminoglycosides should generally be avoided.
Other Nephrotoxic Drugs (e.g., cisplatin, amphotericin B, polymyxin B, vancomycin) · Potential for increased risk for nephrotoxicity.
Neuromuscular blocking agents & General anesthetics · Concomitant use could potentiate neuromuscular blockade.
モニタリング
Efficacy (cultures, clinical signs, WBCs)
Therapeutic drug monitoring (TDM) is highly recommended: Peak level should be at least 40 mcg/mL and the 4-hour trough sample less than 10 mcg/mL
Renal function tests (BUN, creatinine) and urinalysis (USG, casts) pre-therapy and repeated during therapy
Gross monitoring of vestibular or auditory toxicity
過量投与
Should an inadvertent overdosage be administered, three treatments have been recommended:
- **Hemodialysis:** Very effective in reducing serum levels but rarely a viable option for veterinary patients.
- **Peritoneal dialysis:** Will reduce serum levels but is much less efficacious.
- **Complexation:** Complexation of drug with either carbenicillin or ticarcillin (12-20 g/day in humans) is reportedly nearly as effective as hemodialysis.
Susceptible infections (Adults) · 10 mg/kg IM or IV once daily (q24h) · IM/IV · q24h
Susceptible infections (Foals <30 days old) · 20-25 mg/kg IV or IM once daily (q24h) · IV/IM · q24h
Septic joints · 20 mg/kg IV once daily · IV · q24h · Usually used with a penicillin, at least until a definitive culture is obtained.
Uterine infusion · 2 grams mixed with 200 mL sterile normal saline (0.9% sodium chloride for injection) and aseptically infused into uterus daily for 3 consecutive days · Intrauterine · q24h · 3 days
Septic arthritis in foals (adjunctive) · If a single joint is involved, inject 250 mg daily or 500 mg every other day · Intra-articular · q24h or q48h · Frequency is dependent upon how often joint lavage is performed. Use cautiously in multiple joints as toxicity may result.
Regional intravenous limb perfusion (RILP) in standing horses · Usual dosages range from 500 mg-2 grams; dosage must be greater than 250 mg when a cephalic vein is used for perfusion · RILP · Not specified · Careful placement of tourniquets must be performed.
Birds
Sunken eyes/sinusitis in macaws caused by susceptible bacteria · 40 mg/kg IM once or twice daily · IM · q12-24h · May require 2 weeks of treatment · Must also flush sinuses with saline mixed with appropriate antibiotic (10-30 mL per nostril).
Susceptible infections · 15 mg/kg IM or SC q12h · IM/SC · q12h
Gram-negative infections resistant to gentamicin · 15-20 mg/kg (0.015 mg/g) IM once a day or twice a day · IM · q12-24h · Dilute commercial solution.
Susceptible infections (Ratites) · 7.6-11 mg/kg IM twice daily; air cell: 10-25 mg/egg; egg dip: 2000 mg/gallon of distilled water pH of 6 · IM/Topical · BID
SmallMammals
Susceptible infections (Rabbits) · 8-16 mg/kg daily dose (may divide into q8h-q24h) SC, IM or IV. If given IV, dilute into 4 mL/kg of saline and give over 20 minutes. · SC/IM/IV · q8-24h · Increased efficacy and decreased toxicity if given once daily.
Susceptible infections (Fish) · 5 mg/kg IM loading dose, then 2.5 mg/kg every 72 hours for 5 treatments. · IM · q72h · 5 treatments · Mapped to smallMammals array due to schema constraints.
Dogs
Susceptible infections · 15 mg/kg IV q24h or 20 mg/kg SC/IM q24h. In Greyhounds (and potentially other sighthounds) reduce dose to 10 mg/kg IV q24 or 15mg/kg SC/IM q24h. · IV/SC/IM · q24h
Susceptible infections · 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). · Not specified · q24h (or q8h)
Sepsis · 20 mg/kg once daily IV · IV · q24h
Empiric therapy · 15-30 mg/kg · IV/IM/SC · Not specified · Route not specified, assume IV, IM or SC
Reptiles
Susceptible infections (Snakes) · 5 mg/kg IM (forebody) loading dose, then 2.5 mg/kg q72h for 7-9 treatments. · IM · q72h · 7-9 treatments · Commonly used in respiratory infections. Use a lower dose for Python curtus.
Susceptible infections (Gopher snakes) · 5 mg/kg IM loading dose, then 2.5 mg/kg q72h. · IM · q72h · House snakes at high end of their preferred optimum ambient temperature.
Bacterial shell diseases in turtles · 10 mg/kg daily in water turtles, every other day in land turtles and tortoises for 7-10 days. · Not specified · q24h or q48h · 7-10 days · Used commonly with a beta-lactam antibiotic. Recommended to begin therapy with 20 mL/kg fluid injection. Maintain hydration and monitor uric acid levels.
Susceptible infections (Crocodilians) · 2.25 mg/kg IM q 72-96h · IM · q72-96h
Gram-negative respiratory disease · 3.5 mg/kg IM, SC or via lung catheter every 3-10 days for 30 days. · IM/SC/Lung catheter · q3-10d · 30 days