Amikacin
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Bacterial septicaemia (incl. neonatal sepsis) | Adults, paediatrics, neonates | Monotherapy or combination | FDA Approved |
| Serious respiratory tract infections | Adults & paediatrics | Combination | FDA Approved |
| Bone and joint infections | Adults & paediatrics | Combination | FDA Approved |
| CNS infections (meningitis) | Adults & paediatrics | Combination | FDA Approved |
| Skin and soft tissue infections (incl. burns) | Adults & paediatrics | Monotherapy or combination | FDA Approved |
| Intra-abdominal infections (peritonitis) | Adults & paediatrics | Combination | FDA Approved |
| Complicated urinary tract infections | Adults & paediatrics | Monotherapy | FDA Approved |
Amikacin is a semi-synthetic aminoglycoside derived from kanamycin with a uniquely broad resistance profile. The L-hydroxyaminobutyryl amide (L-HABA) modification at the N-1 position protects amikacin from most aminoglycoside-inactivating enzymes that confer resistance to gentamicin and tobramycin, making it the aminoglycoside of choice when resistance to other agents in the class is suspected. Its FDA-approved spectrum includes Pseudomonas species, E. coli, Proteus species, Providencia, Klebsiella-Enterobacter-Serratia species, and notably Acinetobacter species. Like other aminoglycosides, amikacin lacks reliable activity against streptococci, most enterococci (alone), and anaerobes.
Non-tuberculous mycobacterial (NTM) infections: Amikacin is a cornerstone of multi-drug regimens for M. avium complex (MAC), M. abscessus, M. fortuitum, and M. chelonae infections. Liposomal inhaled amikacin (ARIKAYCE) is FDA-approved for MAC lung disease. Parenteral amikacin is used per ATS/IDSA NTM guidelines. Evidence quality: High.
Multi-drug resistant tuberculosis (MDR-TB): Second-line injectable agent in MDR-TB regimens when the isolate is susceptible. Used per WHO guidelines. Evidence quality: High.
Extended-interval (once-daily) dosing for serious gram-negative infections: 15 mg/kg IV q24h; widely adopted in clinical practice and supported by meta-analyses. Evidence quality: High.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Serious gram-negative infection — traditional dosing | 7.5 mg/kg IV/IM q12h | Adjusted by TDM | 15 mg/kg/day (max 1.5 g/day) | FDA PI: 15 mg/kg/day in 2 or 3 equal doses (7.5 mg/kg q12h or 5 mg/kg q8h). Infuse IV over 30–60 min Peak (30–90 min post-dose): avoid >35 µg/mL. Trough: avoid >10 µg/mL |
| Serious gram-negative infection — extended-interval (once-daily) dosing | 15 mg/kg IV q24h | Guided by levels / nomogram | 15 mg/kg/dose (max 1.5 g) | Widely used in clinical practice; Cmax:MIC ≥8–10 target Extended-interval trough target <2.5 µg/mL. Not for endocarditis, burns, pregnancy, ascites, or CrCl <20 mL/min |
| Uncomplicated urinary tract infection | 250 mg IV/IM q12h | 250 mg q12h | 500 mg/day | FDA PI: 250 mg BID for uncomplicated UTI Reserve for resistant organisms only; aminoglycosides not first-line for UTI |
| MDR-TB or NTM infection — parenteral component | 15 mg/kg IV/IM q24h | Guided by levels | 1–1.5 g/day | Part of multi-drug regimen; duration often months ATS/IDSA: consider 3×/week dosing after initial daily phase to reduce toxicity in prolonged courses |
| Renal impairment — any indication | Loading dose 7.5 mg/kg | Reduce dose or extend interval per CrCl and levels | Per TDM | Interval (h) ≈ serum creatinine (mg/dL) × 9 (FDA PI). Removed by haemodialysis and peritoneal dialysis Half-life ~50 h in ESRD; supplement after dialysis |
| Obesity (BMI ≥30) | Use adjusted body weight: ABW = IBW + 0.4 × (TBW − IBW). Amikacin distributes in extracellular fluid and does not penetrate adipose tissue proportionally Do not exceed 1.5 g/day regardless of weight | |||
Paediatric & Neonatal Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Newborns — serious infection | Loading dose 10 mg/kg | 7.5 mg/kg IV q12h | 15 mg/kg/day | FDA PI dosing. Neonates have larger Vd and prolonged t½ Extended-interval (15 mg/kg q24–48h) used in clinical practice; guided by GA, postnatal age, and levels |
| Children and older infants — serious infection | 15 mg/kg/day in 2–3 divided doses | Adjusted by levels | 15 mg/kg/day | FDA PI: 7.5 mg/kg q12h or 5 mg/kg q8h; same as adult dosing Duration 7–10 days; infants receive 1–2 hour infusion |
Amikacin is dosed at approximately 3× higher mg/kg than gentamicin or tobramycin, and its TDM targets are proportionally higher. For traditional dosing: peak 20–35 µg/mL (drawn 30–90 min post-dose; avoid >35 µg/mL per FDA PI), trough <10 µg/mL (avoid >10 per FDA PI). For extended-interval dosing: trough <2.5 µg/mL. These targets are NOT interchangeable with gentamicin/tobramycin targets (peak <12, trough <2). The clinical efficacy target is Cmax:MIC ≥8–10. The FDA PI recommends measuring levels intermittently during therapy and adjusting dosage accordingly. Safety beyond 14 days of treatment has not been established.
Pharmacology
Mechanism of Action
Amikacin is a semi-synthetic aminoglycoside derived from kanamycin A by acylation of the 1-amino group with L-4-amino-2-hydroxybutyryl. Like other aminoglycosides, it irreversibly binds to the 16S rRNA of the 30S ribosomal subunit, causing misreading of the genetic code and inhibiting protein synthesis. This produces aberrant proteins that are inserted into the bacterial cell membrane, increasing permeability and triggering rapid cell death. The L-HABA side chain at N-1 sterically protects amikacin from the majority of aminoglycoside-modifying enzymes (acetyltransferases, phosphotransferases, and nucleotidyltransferases) that inactivate gentamicin and tobramycin, explaining its wider resistance profile. Amikacin exhibits concentration-dependent bactericidal activity with a Cmax:MIC ratio of 8–10 as the primary pharmacodynamic predictor of efficacy, and a post-antibiotic effect (PAE) of 1–3 hours against susceptible gram-negatives.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Negligible oral; 100% via IV/IM; Tmax 0.5–2 h (IM); peak ~20 µg/mL after 7.5 mg/kg IM dose | Must be given parenterally for systemic infections; no oral formulation |
| Distribution | Vd ~0.25 L/kg; ECF distribution; renal cortex concentrations ~10× plasma; distributes to heart, gallbladder, lungs, bone; poor CSF penetration (10–20% plasma in infants; up to 50% with meningitis); crosses placenta | Vd increased in burns, sepsis, ascites; low CSF levels may require intrathecal dosing; avoid intraocular use (macular infarction reported) |
| Metabolism | Not metabolised; excreted as unchanged drug | No hepatic dose adjustment; no CYP450 interactions |
| Elimination | t½ 2–3 h (normal renal function); ~50 h in ESRD; 95–99% excreted unchanged in urine via glomerular filtration within 24 h; 1–2% biliary; removed by haemodialysis and peritoneal dialysis | Half-life directly proportional to renal impairment; renal cortex retention for weeks (basis for nephrotoxicity); removable by both haemodialysis and peritoneal dialysis (unlike gentamicin which is poorly removed by PD) |
Side Effects
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nephrotoxicity (rising BUN/SCr, proteinuria, oliguria, electrolyte wasting) | 1–10% (clinically significant); BUN/Cr elevations in 5–25% | Proximal tubular necrosis; risk factors: trough >10 µg/mL, cumulative dose, concurrent nephrotoxins, dehydration. Generally reversible with early detection (FDA PI). BUN/Cr laboratory increases are common but not all represent clinical nephrotoxicity |
| Ototoxicity (auditory — high-frequency hearing loss) | 4–6% | Primarily auditory (cochlear) damage; usually irreversible. Risk with high doses, prolonged therapy, renal impairment, concurrent ototoxins (StatPearls) |
| Vestibulotoxicity (dizziness, vertigo, ataxia) | ~3–5% | Can occur independently of auditory damage; may be permanent |
| Eosinophilia | Reported | Haematological change noted in FDA PI adverse reactions section |
| Hypomagnesaemia | Reported | Renal tubular magnesium wasting; may cause tetany and arrhythmias (FDA PI) |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Irreversible sensorineural hearing loss | 4–6% | Days to weeks; may manifest after therapy ends | Baseline and serial audiometry; discontinue at first sign of hearing changes. Pre-existing renal damage is the strongest risk factor (FDA PI) |
| Acute kidney injury / renal failure | 1–10% | Days into therapy | Monitor SCr daily; reduce dose or discontinue if rising; ensure hydration; generally reversible (FDA PI) |
| Neuromuscular blockade / respiratory paralysis | Rare | During or shortly after administration; also after topical irrigation | IV calcium salts for reversal; mechanical ventilation if needed. Irreversible deafness, renal failure, and death have been reported following surgical irrigation (FDA PI) |
| Macular infarction / permanent vision loss | Reported | Post-intravitreous injection | Amikacin injection is NOT approved for intraocular use (FDA PI) |
Amikacin nephrotoxicity results from drug accumulation in proximal tubular lysosomes, causing phospholipidosis and cell death. Risk factors include trough levels above 10 µg/mL, cumulative dose, concurrent nephrotoxic drugs (vancomycin, amphotericin B, cisplatin, cephalosporins), dehydration, and advanced age. Maintaining adequate hydration and monitoring daily serum creatinine, electrolytes (Mg, Ca, K), and urinalysis during the first week are essential. Extended-interval dosing may reduce nephrotoxicity by saturating tubular uptake mechanisms and allowing a drug-free recovery interval.
Drug Interactions
Amikacin is not metabolised and has low protein binding, so CYP450 or displacement interactions are absent. Clinically significant interactions are pharmacodynamic (additive toxicity) with other nephrotoxic, ototoxic, or neuromuscular blocking agents.
Monitoring
- Serum Drug Levels (TDM)Intermittently during therapy
RoutineTraditional: peak 20–35 µg/mL (30–90 min post-dose; avoid >35), trough <10 µg/mL (just before next dose; avoid >10). Extended-interval: trough <2.5 µg/mL. These targets differ from gentamicin/tobramycin. Measure after 2–3 doses and periodically thereafter (FDA PI). - Renal Function (BUN, SCr, CrCl)Baseline, daily first week, then twice weekly
RoutineFDA PI notes BUN is less reliable than SCr for monitoring. Monitor urinalysis (casts, protein, cells) as early markers. Rising SCr warrants dose adjustment or discontinuation. - Auditory FunctionBaseline audiometry; serial if therapy >7 days or high-risk
RoutinePre-treatment audiogram recommended. High-frequency hearing loss occurs first and may initially be subclinical. Tinnitus is a sentinel symptom. Ototoxicity described as “permanent in a significant proportion of patients” in the FDA PI. - Vestibular FunctionThroughout therapy
RoutineMonitor for dizziness, vertigo, nystagmus, ataxia. May be independent of auditory damage. - Electrolytes (Mg, Ca, K)Baseline, then twice weekly
RoutineRenal tubular wasting of Mg, Ca, K reported. Hypomagnesaemia can cause tetany and arrhythmias (FDA PI). - Neuromuscular FunctionIn operative/ICU settings
Trigger-basedParticularly in patients receiving NMBAs, anaesthetics, or citrate-anticoagulated blood transfusions. Have IV calcium available (FDA PI).
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to amikacin or any aminoglycoside — cross-allergenicity exists across the class (FDA PI).
Relative Contraindications (Specialist Input Recommended)
- Pre-existing significant renal impairment — intensified TDM and dose individualisation required.
- Pre-existing auditory or vestibular impairment — baseline audiometry essential.
- Pregnancy — aminoglycosides cross the placenta; irreversible congenital deafness reported. Use only if benefit clearly outweighs risk (FDA PI).
- Myasthenia gravis — risk of neuromuscular blockade and respiratory failure.
Use with Caution
- Elderly patients — reduced renal function may not be reflected by SCr alone; use CrCl-based dosing.
- Premature and neonatal infants — renal immaturity prolongs half-life; use with caution (FDA PI).
- Dehydration — ensure adequate hydration to reduce nephrotoxicity risk.
- Concurrent nephro-/ototoxic agents — avoid concurrent or sequential use when possible.
- Topical irrigation of surgical fields — aminoglycosides are almost completely absorbed; irreversible deafness, renal failure, and death from NMB have been reported (FDA PI).
- Obesity — use adjusted body weight; max 1.5 g/day.
Amikacin is potentially nephrotoxic, ototoxic, and neurotoxic. Neurotoxicity manifested as vestibular and permanent bilateral auditory ototoxicity can occur in patients with pre-existing renal damage and in those treated at higher doses or for periods longer than recommended. Safety beyond 14 days has not been established. Peak concentrations above 35 µg/mL and trough concentrations above 10 µg/mL should be avoided. Concurrent or serial use of other ototoxic or nephrotoxic agents should be avoided. Aminoglycosides can cause fetal harm when administered to a pregnant woman. Irreversible deafness, renal failure, and death from neuromuscular blockade have been reported following irrigation of surgical fields.
Patient Counselling
Purpose of Therapy
Amikacin is a powerful antibiotic used to treat serious bacterial infections, particularly those caused by organisms resistant to other antibiotics. It is given by injection or intravenous infusion in a hospital or supervised clinical setting. Regular blood tests are required to monitor drug levels and kidney function. It does not treat viral infections.
How to Take
Amikacin is administered by healthcare professionals. The typical treatment course is 7 to 10 days. Complete the full course as prescribed even if symptoms improve early. Skipping doses or stopping treatment prematurely may allow bacteria to develop resistance.
Sources
- Amikacin Sulfate Injection, USP — Full Prescribing Information (Fresenius Kabi). DailyMed LabelPrimary FDA label source for all dosing, TDM targets, indications, boxed warnings, and adverse reactions.
- Amikacin Sulfate Injection, USP — Full Prescribing Information (Sagent Pharmaceuticals). DailyMed LabelAlternate FDA label providing additional clinical context and adverse reaction detail.
- Hatala R, Dinh T, Cook DJ. Once-daily aminoglycoside dosing in immunocompetent adults: a meta-analysis. Ann Intern Med. 1996;124(8):717–725. doi:10.7326/0003-4819-124-8-199604150-00003Meta-analysis supporting extended-interval aminoglycoside dosing as at least as effective and no more toxic than traditional dosing.
- Barza M, Ioannidis JPA, Cappelleri JC, Lau J. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ. 1996;312(7027):338–345. doi:10.1136/bmj.312.7027.338Independent meta-analysis confirming similar efficacy and possible reduced nephrotoxicity with once-daily aminoglycoside dosing.
- Smith CR, Lipsky JJ, Laskin OL, et al. Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med. 1980;302(20):1106–1109. doi:10.1056/NEJM198005153022002Landmark aminoglycoside toxicity study establishing comparative nephro- and ototoxicity incidence data relevant to the entire class.
- Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Clin Infect Dis. 2020;71(4):e1–e36. doi:10.1093/cid/ciaa241ATS/IDSA guideline positioning parenteral amikacin in multi-drug regimens for MAC, M. abscessus, and other NTM infections.
- WHO consolidated guidelines on tuberculosis. Module 4: treatment — drug-resistant tuberculosis treatment, 2022 update. Geneva: WHO; 2022. WHO PublicationWHO guideline positioning amikacin as a second-line injectable for MDR-TB when isolate susceptibility is confirmed.
- Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the SIS and IDSA. Clin Infect Dis. 2010;50(2):133–164. doi:10.1086/649554SIS/IDSA guideline including aminoglycoside options for empiric combination therapy in cIAI.
- Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987;155(1):93–99. doi:10.1093/infdis/155.1.93Established the Cmax:MIC ratio as the key PK/PD predictor of aminoglycoside clinical efficacy.
- Lacy MK, Nicolau DP, Nightingale CH, Quintiliani R. The pharmacodynamics of aminoglycosides. Clin Infect Dis. 1998;27(1):23–27. doi:10.1086/514620Key review of concentration-dependent killing and post-antibiotic effect principles supporting extended-interval dosing.
- Bauer LA, Blouin RA. Amikacin pharmacokinetics: wide interpatient variation in 98 patients. J Clin Pharmacol. 1983;23(2-3):123–130. doi:10.1002/j.1552-4604.1983.tb02713.xDemonstrated wide inter-patient variability in amikacin PK (Vd 0.08–0.48 L/kg, t½ 0.68–14.4 h), reinforcing the need for individualised TDM.
- Traynor AM, Nafziger AN, Bertino JS Jr. Aminoglycoside dosing weight correction factors for patients of various body sizes. Antimicrob Agents Chemother. 1995;39(2):545–548. doi:10.1128/AAC.39.2.545Established the 0.4 correction factor for adjusted body weight dosing in obese patients receiving aminoglycosides.
- Touw DJ, Westerman EM, Sprij AJ. Therapeutic drug monitoring of aminoglycosides in neonates. Clin Pharmacokinet. 2009;48(2):71–88. doi:10.2165/0003088-200948020-00001Comprehensive review of neonatal aminoglycoside PK and TDM strategies.
- Rybak MJ, Abate BJ, Kang SL, Ruffing MJ, Lerner SA, Drusano GL. Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity. Antimicrob Agents Chemother. 1999;43(7):1549–1555. doi:10.1128/AAC.43.7.1549Prospective study comparing extended-interval vs traditional dosing for nephrotoxicity and ototoxicity outcomes.