Amikacin
Amikacin is a bactericidal aminoglycoside antibiotic used mainly for serious infections caused by susceptible aerobic gram-negative bacteria. It may remain active against some organisms resistant to gentamicin because it is less vulnerable to several aminoglycoside-inactivating enzymes. This advantage is organism-specific and does not replace susceptibility testing.
Systemic treatment generally requires parenteral administration because gastrointestinal absorption is negligible. Equine applications also include regional limb perfusion and selected intrauterine treatment. Its predominantly extracellular distribution and renal elimination are central to both its clinical use and its toxicity profile.
Group
Aminoglycoside antibacterial
Mechanism of Action
Amikacin enters susceptible bacteria through uptake processes that depend partly on oxygen-linked metabolism. It binds to the 30S ribosomal subunit, disrupts initiation and accuracy of translation, and causes production of abnormal proteins. Membrane injury and further drug entry contribute to a bactericidal effect rather than simple reversible growth suppression.
Killing is concentration-dependent, and suppression can persist after concentrations fall below the organism’s inhibitory concentration. Poor uptake in anaerobic conditions helps explain the lack of reliable anaerobic coverage; activity is also reduced in some purulent, acidic or poorly perfused environments.
Amikacin is less susceptible than some other aminoglycosides to particular bacterial drug-modifying enzymes, but resistance can still arise. Filtration and accumulation in renal tissues, and effects on inner-ear structures, account for important host toxicity; high antibacterial activity does not imply low nephrotoxic or ototoxic potential.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 15 mg/kg | IV, IM, SC | Every 24 h | Do not use in: Dehydration |
| Susceptible infection – higher extravascular regimen | 20 mg/kg | IM, SC | Every 24 h | |
| Sighthound bacterial infection | 10 mg/kg | IV | Every 24 h | Greyhounds and potentially other sighthounds have smaller distribution volumes. |
| Sighthound bacterial infection | 15 mg/kg | IM, SC | Every 24 h | Greyhounds and potentially other sighthounds. |
| Sepsis | 20 mg/kg | IV | Every 24 h | |
| Empirical infection – interval unspecified | 15–30 mg/kg | IV | The empirical entry permits assumed IV/IM/SC routes, but gives no repeat interval for this empirical range; not a completed schedule. |
Cats
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 10 mg/kg | IV, IM, SC | Every 24 h | Do not use in: Dehydration |
| Sepsis | 20 mg/kg | IV | Every 24 h | |
| Empirical infection – interval unspecified | 10–15 mg/kg | IV | The empirical entry permits assumed IV/IM/SC routes, but gives no repeat interval for this empirical range; not a completed schedule. |
Horses
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 10 mg/kg | IV, IM | Every 24 h | Do not use in: Dehydration; Adult horses. |
| Neonatal bacterial infection | 20 mg/kg | IV | Every 24 h | Do not use in: Dehydration; Foals. |
| Regional limb perfusion | 125–500 mg | IV | Do not use in: Dehydration; Amount per limb, diluted in 60 mL saline; regional perfusion is not ordinary systemic IV administration. | |
| Susceptible infection – 21 mg/kg alternative | 21 mg/kg | IV, IM | Every 24 h | |
| Neonatal infection – 21 mg/kg alternative | 21 mg/kg | IV | Every 24 h | Neonatal foals. |
| Neonatal infection – individualized initial dose — Initial | 25 mg/kg | IV | Every 24 h | Neonatal foals; individualize subsequent amounts using drug monitoring. |
| Foal infection – alternative | 20–25 mg/kg | IV, IM | Every 24 h | Foals younger than 30 days. |
| Septic arthritis – systemic adjunct | 20 mg/kg | IV | Every 24 h | Usually combined with a penicillin until culture results are available. |
Cattle
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 10 mg/kg | IV, IM, SC | Every 24 h | Do not use in: Food-producing animals, Dehydration; Adults; not recommended in food-producing animals. |
| Neonatal bacterial infection | 20 mg/kg | IV, IM | Every 24 h | Do not use in: Food-producing animals, Dehydration; Calves younger than 2 weeks; not recommended in food-producing animals. |
| Susceptible infection – frequent alternative | 10 mg/kg | IM | Every 8 h | Do not use in: Food-producing animals |
| Susceptible infection – twice-daily alternative | 25 mg/kg | IM | Every 12 h | Do not use in: Food-producing animals; IM route is inherited from the paired cattle entry. |
| Susceptible infection – divided daily alternative | 22 mg/kg | IM | Do not use in: Food-producing animals; Total daily amount divided into 3 administrations; do not give 22 mg/kg at each administration. |
Ferret
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 8–16 mg/kg | IM, IV | Every 24 h | |
| Susceptible infection – divided daily amount | 8–16 mg/kg | SC | Total daily amount divided every 8–24 hours by SC, IM or IV routes; not a per-administration range. |
Rabbit
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible infection – divided daily amount | 8–16 mg/kg | SC | Total daily amount may be divided every 8–24 hours using SC, IM or IV administration. Rabbit use carries a gastrointestinal-flora warning; for rabbit IV treatment dilute into 4 mL/kg saline and administer over 20 minutes. |
Guinea pigs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible infection – divided daily amount | 10–15 mg/kg | SC | Daily amount divided every 8–24 hours using SC, IM or IV administration; do not apply the full daily amount at each interval. |
Chinchilla
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible infection – divided daily amount | 10–15 mg/kg | SC | Daily amount divided every 8–24 hours using SC, IM or IV administration; do not apply the full daily amount at each interval. | |
| Susceptible infection – low-dose alternative | 2–5 mg/kg | SC, IM | Every 8–12 h |
Hamster
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 10 mg/kg | SC, IM | Every 12 h |
Rat
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 10 mg/kg | SC, IM | Every 12 h |
Mouse
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 10 mg/kg | SC, IM | Every 12 h |
Prairie dog
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 5 mg/kg | SC, IM | Every 12 h |
Macaw
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial sinusitis | 40 mg/kg | IM | Every 12–24 h | Up to 14 days; Also flush each nostril with 10–30 mL saline containing an appropriately selected antibiotic. |
Bird
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 15 mg/kg | IM, SC | Every 12 h | |
| Gentamicin-resistant infection | 15–20 mg/kg | IM | Every 12–24 h | Dilute the injection appropriately for the small administration volume. |
Ratite
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 7.6–11 mg/kg | IM | Every 12 h |
Snake
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection — Loading | 5 mg/kg | IM | Once | For snakes, inject in the forebody; use a lower dose for Python curtus. |
| Susceptible bacterial infection — Maintenance | 2.5 mg/kg | IM | Every 72 h | 7–9 treatments; maintain the upper end of the preferred environmental temperature range. |
Fish
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection — Loading | 5 mg/kg | IM | Once | For snakes, inject in the forebody; use a lower dose for Python curtus. |
| Susceptible bacterial infection — Maintenance | 2.5 mg/kg | IM | Every 72 h | 5 treatments. |
Crocodilian
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Susceptible bacterial infection | 2.25 mg/kg | IM | Every 72–96 h |
Reptile
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Gram-negative respiratory infection | 3.5 mg/kg | IM, SC | Every 72–240 h | Up to 30 days; A lung-catheter alternative requires a dedicated local protocol. |
Indications
- Treatment of serious infections caused by susceptible aerobic gram-negative bacteria, including selected organisms resistant to gentamicin.
- Culture-directed treatment of severe bacterial infections at sites where adequate aminoglycoside exposure can be achieved.
- Equine regional limb perfusion for selected distal-limb infections as an adjunct to systemic or surgical management.
- Selected equine intrauterine treatment of susceptible bacterial genital-tract infection.
Contraindications
- Aminoglycoside hypersensitivity.
- Renal impairment and dehydration markedly increase toxicity risk; correct dehydration and use individualized intervals with drug monitoring if treatment is essential.
- Neonates, geriatric animals, sepsis, fever and neuromuscular disease increase risk.
- Generally avoid in rabbits and hares because intestinal flora may be disrupted.
- Avoid in food-producing animals because of prolonged tissue residues.
Interactions
- Do not mix with other drugs or antibiotics in a syringe or vial.
- Neuromuscular blockade may occur with anesthetic agents.
- Loop or osmotic diuretics may increase auditory and renal toxicity.
- Other nephrotoxins, including amphotericin, cisplatin and polymyxins, increase renal risk; NSAIDs also warrant caution.
Adverse effects
- Dose-limiting nephrotoxicity.
- Auditory and vestibular toxicity.
Toxicity
Overdose can cause renal, auditory, vestibular and neuromuscular toxicity. Hemodialysis removes systemic drug effectively; peritoneal dialysis is less efficient. Monitor renal function and hearing/vestibular signs.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Amikacin 50 mg/mL injection | Injection | 50 mg / mL | IV, IM, SC |
| Amikacin 250 mg/mL injection | Injection | 250 mg / mL | IV, IM, SC |
| Grasil 25 mg per 1 mL injection SAMI Pharmaceuticals (Pvt.) Ltd. Amikacin-equivalent strength from sulfate; give separately from other drugs. Use diluted solution promptly; do not store. | Injection | 25 mg / mL | IM, IV |
| Grasil 50 mg per 1 mL injection SAMI Pharmaceuticals (Pvt.) Ltd. Amikacin-equivalent strength from sulfate; give separately from other drugs. Use diluted solution promptly; do not store. | Injection | 50 mg / mL | IM, IV |
| Grasil 100 mg per 2 mL injection SAMI Pharmaceuticals (Pvt.) Ltd. Amikacin-equivalent strength from sulfate; give separately from other drugs. Use diluted solution promptly; do not store. | Injection | 100 mg / 2 mL | IM, IV |
| Grasil 250 mg per 2 mL injection SAMI Pharmaceuticals (Pvt.) Ltd. Amikacin-equivalent strength from sulfate; give separately from other drugs. Use diluted solution promptly; do not store. | Injection | 250 mg / 2 mL | IM, IV |
| Grasil 500 mg per 2 mL injection SAMI Pharmaceuticals (Pvt.) Ltd. Amikacin-equivalent strength from sulfate; give separately from other drugs. Use diluted solution promptly; do not store. | Injection | 500 mg / 2 mL | IM, IV |
Monitoring and Administration
Maintain fluid and electrolyte balance. Monitor BUN, creatinine and urinalysis; consider therapeutic drug monitoring. With once-daily treatment, troughs should become undetectable.
Samples at 1 hour and 2–4 hours can characterize clearance; typical clearance exceeds 1 mL/kg/min and half-life is under 2 hours.
Protect from light in a tightly closed container at room temperature; admixture with other drugs can cause instability.
Equine intrauterine infection: Intrauterine route, not cutaneous: dilute 2 g (8 mL of 250 mg/mL) in 200 mL sterile saline. This is a local uterine procedure, not systemic administration. Treat once daily for 3 days.
Susceptibility criteria are MIC ≤4 mcg/mL for dogs and horses and ≤2 mcg/mL for foals; the canine criterion may be applied to feline isolates. Interpret susceptibility against the applicable species, site and current laboratory method.
Dog divided-dose alternative: a total 15 mg/kg per day is described, with division every 8 hours for selected neutropenic or immunocompromised patients; route is not specified for that alternative. Individualize by drug monitoring rather than applying the once-daily amount three times daily.
Cat divided-dose alternative: a total 15 mg/kg per day is described, with division every 8 hours for selected neutropenic or immunocompromised patients; route is not specified for that alternative. Individualize by drug monitoring rather than applying the once-daily amount three times daily.
Equine local procedures: an additional intrauterine amount is 1–2 g, without a complete dilution or schedule. For one septic foal joint, 250 mg intra-articularly daily or 500 mg every other day is described; lavage frequency guides repetition. Multiple-joint injection, especially with systemic treatment, can increase toxicity. Regional IV perfusion alternatives use 500–2000 mg; when perfusing via a cephalic vein the amount should exceed 250 mg and tourniquet placement is critical.
Ratite egg procedures use 10–25 mg per egg by air-cell administration or an egg dip containing 2000 mg per gallon distilled water at pH 6. These are egg procedures, not systemic bird doses.
Turtle shell infection alternatives use 10 mg/kg daily for aquatic turtles or every other day for terrestrial turtles/tortoises for 7–10 days; route is not specified. A 20 mL/kg fluid injection before treatment, maintenance of hydration and uric-acid monitoring are described, often with a beta-lactam.
For systemic drug monitoring, an additional sampling plan is 1, 2 and 4 hours after dosing, targeting a peak at least 40 mcg/mL and a 4-hour concentration below 10 mcg/mL. This does not replace an undetectable trough target. Freeze delayed samples when concomitant beta-lactams could inactivate drug in vitro. Give IV preparations diluted in a compatible fluid over at least 30 minutes.