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Amikacin

Grade

Sensitive Infections

Protocol(s) for Sensitive Infections

  • Our Recommendation: 5mg/kg SC/IM/IV q 12-24h

  • Dosing Interval: Amikacin is a concentration-dependent antimicrobial, and increased efficacy and decreased toxicity are proposed when higher doses are administered less frequently.  Where renal sensitivity is a consideration, increase dosing frequency to q36h or q48h (Matsumoto et al., 1982; Mayers et al., 1991; Staneva et al., 1994). 

  • Hydration: Animals should remain well hydrated through treatment, and intravenous fluids are recommended in debilitated patients where practical.

Other Suggestions

  • The literature review reveals many proposed doses and dosing frequencies. The range identified was 2-20 mg/kg, SC, IV, IM, q 8-24h (Carpenter and Harms, 2023; Hedley and BSAVA, 2023; Smith, 2022). 

Therapeutics

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Significant Adverse Effects

  • Nephrotoxicity: These are usually reversible when the drug is discontinued. Reports of toxic nephropathy and acute renal failure have been received during postmarketing surveillance.

  • Ototoxicity: Toxic effects on the eighth cranial nerve can result in hearing loss, loss of balance, or both.

Significant Contraindications

  • Dehydration: Do not use in hypovolaemic animals or those with impaired glomerular filtration.

  • Pre-existing Renal Disease: Avoid use in Chronic Kidney Disease (CKD) and Acute Kidney Injury (AKI)

  • Allergy, hypersensitivity: Amikacin sulphate injection is contraindicated in patients with known allergy to amikacin or any formulation component.

  • Myasthenia gravis: Aminoglycosides may impair neuromuscular transmission and should not be given to patients with myasthenia gravis.

Significant Interactions

  • Anaesthetics: Potential for neuromuscular blockade.

  • Cephalosporins: Potential for additive nephrotoxicity and potential for synergistic effect with first or second-generation agents

  • Loop Diuretics (Furosemide, Torsemide): increased potential for nephrotoxic or ototoxic effects

  • Osmotic Diuretics  (e.g., mannitol): increased potential for nephrotoxic or ototoxic effects

  • NSAIDs: Increased risk of nephrotoxicity

  • Penicillins: Potential for a synergistic effect.

Reproductive Safety

  • Pregnancy: Avoid use; potential for harm. In zebrafish, amikacin induced embryonic toxicity and reduced survival rate

  • Lactation: Amikacin is poorly excreted into milk.

  • Fertility: Amikacin administered subcutaneously to rats did not impair male or female fertility.

  • Carcinogenicity and mutagenicity: Long-term animal studies have not been performed to evaluate carcinogenic potential and mutagenicity.

Duration of Therapy

  • Treatment Targets: TTs are usually case-specific but should be agreed upon within the multidisciplinary team early in the treatment period. 

  • Treatment Endpoint: TE is generally the achievement of case-specific treatment targets. A suitable endpoint is generally the resolution of the presentation or identification of intolerable adverse effects.  

  • Typical Treatment Periods: No TTP data located.

Therapeutic Monitoring 

  • Efficacy: Signs of efficacy are patient-specific and associated with the infection under treatment.

  • Renal  Effects:  Renal function and IRIS staging/Urine specific gravity

  • Sensory Monitoring: Auditory toxicity assessment is subjective but should be considered before, during, and after aminoglycoside treatment.

Efficacy Data

All antimicrobials should have therapeutic sensitivity confirmed before treatment and clinical response monitored throughout treatment.  


  • Sensitivity: Typically, culture/E screening or target organism identification.  

  • Clinical Response: Typically, clinical signs associated with the specific infection and surveillance include laboratory parameters such as renal markers and the leucogram. 

Evidence

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  1. Abdel-Daim, M.M., Ahmed, A., Ijaz, H., Abushouk, A.I., Ahmed, H., Negida, A., Aleya, L., Bungau, S.G., 2019. Influence of Spirulina platensis and ascorbic acid on amikacin-induced nephrotoxicity in rabbits. Environ Sci Pollut Res Int 26, 8080–8086. https://doi.org/10.1007/s11356-019-04249-4

  2. Bayer, A.S., Lam, K., Norman, D., Kim, K.S., Morrison, J.O., 1985. Amikacin + ceftazidime therapy of experimental right-sided Pseudomonas aeruginosa endocarditis in rabbits. Chemotherapy 31, 351–361. https://doi.org/10.1159/000238359

  3. Benato, L., 2017. Odontogenic abscesses in pet rabbits. Veterinary Record 181, 536–537. https://doi.org/10.1136/vr.j5249

  4. Dubé, L., Caillon, J., Jacqueline, C., Bugnon, D., Potel, G., Asseray, N., 2012. The optimal aminoglycoside and its dosage for the treatment of severe Enterococcus faecalis infection. An experimental study in the rabbit endocarditis model. Eur J Clin Microbiol Infect Dis 31, 2545–2547. https://doi.org/10.1007/s10096-012-1594-x

  5. Espitalier, F., Darrouzain, F., Escoffre, J.-M., Ternant, D., Piver, E., Bouakaz, A., Remerand, F., 2019. Enhanced Amikacin Diffusion With Ultrasound and Microbubbles in a Mechanically Ventilated Condensed Lung Rabbit Model. Front Pharmacol 10, 1562. https://doi.org/10.3389/fphar.2019.01562

  6. Gardhouse, S., Sanchez-Migallon Guzman, D., Paul-Murphy, J., Byrne, B.A., Hawkins, M.G., 2017. Bacterial isolates and antimicrobial susceptibilities from odontogenic abscesses in rabbits: 48 cases. Vet Rec 181, 538. https://doi.org/10.1136/vr.103996

  7. Harrison, Z.L., Pace, L.R., Brown, M.N., Beenken, K.E., Smeltzer, M.S., Bumgardner, J.D., Haggard, W.O., Amber Jennings, J., 2021. Staphylococcal infection prevention using antibiotic-loaded mannitol-chitosan paste in a rabbit model of implant-associated osteomyelitis. J Orthop Res 39, 2455–2464. https://doi.org/10.1002/jor.24986

  8. Huh, J., Chen, J.C., Furman, G.M., Malki, C., King, B., Kafie, F., Wilson, S.E., 1998. Local treatment of prosthetic vascular graft infection with multivesicular liposome-encapsulated amikacin. J Surg Res 74, 54–58. https://doi.org/10.1006/jsre.1997.5188

  9. Ischanova, Y.S., Rakhmanova, I.V., D’yakonova, I.N., 2019. Effects of Cocarboxylase in Amikacin-Induced Ototoxicity in Immature Animals. Bull Exp Biol Med 167, 250–254. https://doi.org/10.1007/s10517-019-04502-3

  10. Kokkas, B., Kotoula, M., Kouyoumtzis, A., Paradelis, A.G., 1989. The influence of amikacin on digoxin uptake by certain rabbit tissues in vitro. Methods Find Exp Clin Pharmacol 11, 641–642.

  11. Matsumoto, H., Ochiai, K., Nakajima, A., Matsuzaki, M., 1982. [Absorption, excretion and distribution of amikacin following intravenous drip infusion. Intravenous drip infusion, one shot intravenous injection and intramuscular administration of amikacin in dogs, rabbits and rats]. Jpn J Antibiot 35, 2034–2046.

  12. Mayers, M., Rush, D., Madu, A., Motyl, M., Miller, M.H., 1991. Pharmacokinetics of amikacin and chloramphenicol in the aqueous humor of rabbits. Antimicrob Agents Chemother 35, 1791–1798. https://doi.org/10.1128/AAC.35.9.1791

  13. Ohtani, I., Ohtsuki, K., Aikawa, T., Sato, Y., Ouchi, J., Saito, T., 1982. Evaluation of ototoxicity of amino-glycoside antibiotics in rabbits. Auris Nasus Larynx 9, 67–74. https://doi.org/10.1016/s0385-8146(82)80002-3

  14. Robaux, M.A., Dube, L., Caillon, J., Bugnon, D., Kergueris, M.F., Navas, D., Le Conte, P., Baron, D., Potel, G., 2001. In vivo efficacy of continuous infusion versus intermittent dosing of ceftazidime alone or in combination with amikacin relative to human kinetic profiles in a Pseudomonas aeruginosa rabbit endocarditis model. J Antimicrob Chemother 47, 617–622. https://doi.org/10.1093/jac/47.5.617

  15. Staneva, M., Markova, B., Atanasova, I., Terziivanov, D., 1994. Pharmacokinetic and pharmacodynamic approach for comparing two therapeutic regimens using amikacin. Antimicrob Agents Chemother 38, 981–985. https://doi.org/10.1128/AAC.38.5.981

5.2 Additional Material Consulted

  1. Carpenter, J.W., Harms, C.A. (Eds.), 2023. Carpenter’s Exotic Animal Formulary, Sixth edition. ed. Elsevier, St. Louis, Missouri.

  2. Hedley, J., BSAVA (Eds.), 2023. Small Animal Formulary: Part B: Exotic Pets, 11th edition,. ed. BSAVA, British Small Animal Veterinary Association, Quedgeley, Gloucester.

  3. Smith, M., 2022. Textbook of Rabbit Medicine,  3rd Edition, Elsevier Limited.  Available from: vbk://9780702084041.

Monograph Details

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