What is the recommended amikacin dosing regimen for serious respiratory infections in adults and children, including renal‑function adjustments, therapeutic drug monitoring, and typical duration of therapy?

Amikacin Dosing for Respiratory Infections

For serious respiratory infections in adults with normal renal function, administer amikacin 15 mg/kg once daily intravenously, targeting peak serum concentrations of 65–80 mg/L and trough levels below 5 mg/L. 1

Standard Adult Dosing Regimens

Once-Daily Dosing (Preferred)

• Administer 15 mg/kg once daily as a 30-minute IV infusion for adults with preserved renal function. 1, 2
• This regimen achieves superior clinical cure rates (83% vs 66%) and lower nephrotoxicity (21% vs 35%) compared to twice-daily dosing. 3
• For patients over 50 years or those requiring prolonged therapy (≥3 weeks), reduce the dose to 10 mg/kg daily to minimize toxicity. 4

Alternative Twice-Daily Dosing

• If once-daily dosing is not feasible, administer 7.5 mg/kg every 12 hours. 1
• This traditional regimen is associated with higher nephrotoxicity rates and should be reserved for specific clinical scenarios. 3

Three-Times-Weekly Dosing

• For nontuberculous mycobacterial (NTM) pulmonary disease, administer 15–25 mg/kg three times weekly, targeting peak levels of 65–80 mg/L. 4
• This intermittent regimen may be difficult to tolerate beyond 3 months but is reasonable for long-term NTM therapy. 4

Pediatric Dosing

Standard Pediatric Regimens

• For children with serious Gram-negative infections, administer 15–30 mg/kg once daily. 4, 1
• Neonates and infants require a loading dose of 10 mg/kg followed by 7.5 mg/kg every 12 hours. 1
• For children under 1 year, the total daily dose is 20 mg/kg; for older children, use 15 mg/kg daily. 1, 5

Pediatric NTM Infections

• For tuberculosis or NTM disease in children, administer 15–30 mg/kg daily (maximum 1 gram) or 15–30 mg/kg three times weekly. 4

Renal Function Adjustments

Dosing in Renal Impairment

• When creatinine clearance is reduced, extend the dosing interval by multiplying the serum creatinine (mg/dL) by 9 to determine hours between doses. 1
  • Example: If serum creatinine is 2.0 mg/dL, administer the standard 7.5 mg/kg dose every 18 hours.
• Alternatively, reduce the maintenance dose proportionally: Maintenance dose = (observed CrCl / normal CrCl) × loading dose, administered every 12 hours. 1
• Always initiate therapy with a full loading dose (7.5 mg/kg in adults, 10 mg/kg in neonates) regardless of renal function. 1

Obesity Adjustments

• For markedly obese patients, calculate adjusted body weight: ideal body weight + 40% of excess weight. 1, 4
• Male ideal body weight (kg) = 50 + (2.3 × height in cm above 152.4)/2.54 1
• Female ideal body weight (kg) = 45.5 + (2.3 × height in cm above 152.4)/2.54 1

Therapeutic Drug Monitoring

Target Serum Concentrations

• Peak levels (drawn 60–120 minutes post-infusion): 25–35 mg/L for daily dosing; 65–80 mg/L for three-times-weekly dosing. 4, 1
• Trough levels (drawn immediately pre-dose): <5 mg/L to minimize nephrotoxicity. 4, 1
• Avoid peak concentrations above 35 mg/L and trough concentrations above 10 mg/L with daily dosing. 1

Monitoring Frequency

• Obtain peak serum level in the first week of therapy; repeat if clinical response is poor. 4
• Measure trough levels weekly for 4 weeks, then reduce to every 2 weeks once stable. 4
• For once-daily dosing, therapeutic drug monitoring primarily ensures trough concentrations remain low enough to prevent renal toxicity. 4

Sampling Technique

• Draw peak level 90–120 minutes after infusion ends, or use a 60-minute post-infusion sample (which may underestimate true peak). 4
• Plot levels on semilogarithmic paper and extrapolate back to time zero for accurate peak determination. 4

Duration of Therapy

Standard Treatment Duration

• The usual duration is 7–10 days for most serious respiratory infections. 1
• For complicated infections requiring treatment beyond 10 days, re-evaluate the need for continued amikacin and monitor serum levels, renal function, and auditory/vestibular function closely. 1

Extended Therapy for Specific Infections

• For M. abscessus pulmonary disease, administer amikacin combined with high-dose cefoxitin (up to 12 g/day) or imipenem for a minimum of 4 months. 4
• For bone infections caused by NTM, extend therapy to 6 months. 4
• Initial parenteral therapy for NTM should continue for at least 2–4 weeks until clinical improvement is evident. 4

Combination Therapy Considerations

Synergistic Regimens

• For serious skin, soft tissue, and bone infections caused by M. abscessus, combine amikacin with clarithromycin 1,000 mg/day (or azithromycin 250 mg/day) plus cefoxitin or imipenem. 4
• Amikacin is the most active parenteral agent against M. abscessus and should be the cornerstone of combination therapy. 4
• For intra-abdominal infections, amikacin 15–20 mg/kg every 24 hours may be combined with β-lactams or metronidazole. 4

Loading Doses in Critical Illness

• In sepsis and septic shock, administer a full loading dose immediately to rapidly achieve therapeutic levels, as critically ill patients have expanded extracellular volume from fluid resuscitation. 4
• Loading doses are not affected by renal function, though maintenance dosing and frequency require adjustment. 4

Toxicity Monitoring and Prevention

Nephrotoxicity Prevention

• Once-daily dosing reduces nephrotoxicity risk compared to multiple daily doses while maintaining equivalent or superior efficacy. 3, 2
• Monitor serum creatinine weekly; a rise in creatinine occurs in 21% of once-daily patients versus 35% of twice-daily patients. 3
• Ensure adequate hydration and avoid concurrent nephrotoxic agents when possible. 1

Ototoxicity Surveillance

• Ototoxicity (auditory > vestibular) is more common with prolonged use and in older patients. 4
• Although formal audiometry was not performed in key studies, no clinical ototoxicity was observed with once-daily dosing. 3, 2
• If treatment extends beyond 10 days, monitor auditory and vestibular function closely. 1

Electrolyte Monitoring

• Monitor for hypocalcemia, hypomagnesemia, and hypokalemia, which can occur with aminoglycoside therapy. 4

Common Pitfalls and Caveats

Avoid Underdosing

• Failure to achieve adequate peak plasma concentrations on initial dosing is associated with clinical failure for aminoglycosides. 4
• Do not reduce the loading dose in obese patients or those with renal impairment; adjust only maintenance dosing. 1

Recognize Treatment Failure Early

• If no definite clinical response occurs within 3–5 days, discontinue amikacin and recheck antibiotic susceptibility patterns. 1
• Failure may indicate organism resistance or the presence of undrained septic foci requiring surgical intervention. 1

Special Population Considerations

• Elderly patients often have reduced creatinine clearance despite normal serum creatinine; calculate estimated GFR rather than relying on creatinine alone. 6
• For elderly patients, preferentially use 11 mg/kg once daily rather than 15 mg/kg to reduce toxicity risk. 6

NTM-Specific Limitations

• No antibiotic regimen based on in vitro susceptibilities reliably produces long-term sputum conversion for M. abscessus lung disease. 4
• Alternative goals such as symptomatic improvement, radiographic regression, or reduced sputum culture positivity are more realistic than microbiologic cure. 4
• Monotherapy with any agent, including amikacin, is insufficient for NTM pulmonary disease; always use combination therapy. 4