Should Amikacin (amikacin) be administered once daily (od) or twice daily (bd)?

Amikacin Should Be Administered Once Daily (OD)

Amikacin should be administered once daily at 15 mg/kg for most patients with serious infections, as this regimen achieves superior peak concentrations, demonstrates equal or better clinical efficacy, and reduces nephrotoxicity compared to twice-daily dosing. 1, 2, 3

Rationale for Once-Daily Dosing

Pharmacodynamic Advantages

• Aminoglycosides exhibit concentration-dependent killing and a prolonged post-antibiotic effect, making them ideal candidates for once-daily administration. 1
• Once-daily dosing achieves mean peak serum concentrations of 40.9 mg/L (approximately 10× MIC for most Gram-negative bacteria), compared to only 24.4 mg/L (6× MIC) with twice-daily dosing. 4
• The higher peak-to-MIC ratio with once-daily dosing maximizes bacterial killing while allowing a longer drug-free interval that may reduce toxicity. 1, 4

Clinical Efficacy Evidence

• In a randomized trial of 348 critically ill patients, once-daily dosing achieved 83% clinical cure versus 66% with twice-daily dosing (P = 0.001), and 81% bacteriological cure versus 58% (P = 0.005). 3
• A Scandinavian multicenter study of 316 patients found 90% satisfactory clinical response with both regimens, confirming non-inferiority at minimum. 4
• Once-daily dosing at 15 mg/kg demonstrated 83.1% primary success and 83.9% definitive cure in severely infected patients, predominantly in intensive care settings. 5

Safety Profile

• Nephrotoxicity occurred in 21% of patients with once-daily dosing compared to 35% with twice-daily dosing (P = 0.05). 3
• The IDSA guidelines note that once-daily aminoglycoside therapy may reduce the incidence of both nephrotoxicity and ototoxicity. 1
• In comparative studies, nephrotoxic events were similar or lower with once-daily dosing (9 events) versus twice-daily (11 events) among 316 patients. 4

Standard Dosing Algorithm

For Most Adult Patients

• Administer 15 mg/kg IV once daily as a 30-60 minute infusion. 2, 5, 4
• The FDA label supports both divided dosing (7.5 mg/kg q12h or 5 mg/kg q8h) and the equivalent total daily dose given once. 2

For Patients Over 59 Years

• Reduce dose to 10 mg/kg once daily due to increased risk of ototoxicity and nephrotoxicity in elderly patients. 6, 7
• Elderly patients often have reduced creatinine clearance; consider 11 mg/kg as an alternative. 8

For Pediatric Patients

• Children and older infants: 15-30 mg/kg once daily. 6
• Patients under 1 year: 20 mg/kg once daily with a 25 mg/kg loading dose. 3
• Newborns: 10 mg/kg loading dose, then 7.5 mg/kg every 12 hours (twice-daily dosing remains standard for neonates). 2

For Renal Impairment

• Do not reduce the milligram dose—maintain 12-15 mg/kg but extend the dosing interval to every 2-3 days. 6, 9
• For hemodialysis patients, administer after dialysis. 6, 9

Therapeutic Drug Monitoring

Target Levels

• Trough: <5 mg/L to prevent toxicity. 6, 7
• Peak: 25-35 mg/L for daily dosing or 65-80 mg/L for three-times-weekly dosing. 6, 7

Monitoring Schedule

• Measure trough level 1 week after starting therapy. 1
• Check peak levels within the first week, then trough levels weekly for 4 weeks, then every 2 weeks when stable. 7
• Monitor renal function monthly throughout treatment. 1, 7

Safety Monitoring

Baseline Assessment

• Obtain audiogram, vestibular testing, Romberg testing, and serum creatinine before initiating therapy. 6

Ongoing Monitoring

• Perform audiometry intermittently during treatment; ototoxicity is defined as 20 dB loss at any one frequency or 10 dB loss at two adjacent frequencies. 1, 7
• If ototoxicity occurs, discontinue amikacin or reduce dosing frequency, though hearing loss is likely permanent. 1
• Question patients monthly about auditory/vestibular symptoms (tinnitus, vertigo, hearing loss). 6

Special Populations and Cautions

Populations Requiring Caution with Once-Daily Dosing

• The IDSA notes that once-daily aminoglycoside therapy has not been fully evaluated in pregnant women, children, elderly persons, and critically ill patients. 1
• Use once-daily dosing with caution in patients with renal dysfunction, neutropenia, burns, liver disease, or endocarditis. 1
• However, the research evidence from critically ill patients actually supports once-daily dosing in this population. 3

Absolute Contraindications

• Pregnancy: Amikacin is absolutely contraindicated due to risk of fetal nephrotoxicity and congenital hearing loss. 6, 9
• Hypersensitivity to aminoglycosides. 1
• Myasthenia gravis (may impair neuromuscular transmission). 1

Common Pitfalls to Avoid

• Do not use fixed 500 mg doses regardless of weight—this risks underdosing and treatment failure. 6, 7
• Do not continue therapy beyond 10 days without reassessing drug levels and monitoring for toxicity. 6, 2
• Do not reduce the milligram dose in renal impairment; instead extend the dosing interval. 6
• Ensure adequate peak concentrations are achieved: therapeutic peaks occurred in 100% of once-daily patients versus only 44-48% of twice-daily patients in pharmacokinetic studies. 10