Gera Tools

Aminoglycoside Extended-Interval Dosing Nomogram

Tobramycin and amikacin once-daily dosing from patient kidney function

Computes tobramycin or amikacin once-daily extended-interval doses and the recommended dosing interval using the Hartford nomogram approach for creatinine clearance at or above 20 mL/min, with renal-adjusted intervals. For infectious disease pharmacists. It runs free in your browser on Gera Tools, with nothing uploaded.

Last updated Source: Gera Tools

Which dose per kilogram does this use?

It uses the conventional extended-interval doses: 7 mg/kg for tobramycin (and gentamicin) on the Hartford regimen, and 15 mg/kg for amikacin. Multiplying by the dosing weight gives the single high dose that maximises the concentration-dependent killing of these drugs.

Extended-interval (once-daily) aminoglycoside dosing gives a single large dose with a drug-free interval to exploit concentration-dependent killing while limiting toxicity. This tool computes the tobramycin or amikacin dose from body weight and selects the dosing interval from creatinine clearance using the Hartford nomogram bands.

How it works

The dose is weight-based and the interval is set by kidney function:

Tobramycin / gentamicin dose = 7 mg/kg × dosing weight
Amikacin dose                = 15 mg/kg × dosing weight

Interval by creatinine clearance (CrCl):
  CrCl >= 60 mL/min  -> every 24 hours
  CrCl 40-59 mL/min  -> every 36 hours
  CrCl 20-39 mL/min  -> every 48 hours
  CrCl < 20 mL/min   -> use traditional dosing with levels

Use ideal or adjusted body weight, not total weight, because these drugs distribute into lean tissue. A timed level still confirms or extends the interval.

Example and notes

A 70 kg patient with a creatinine clearance of 50 mL/min started on tobramycin receives 490 mg (7 mg/kg) given every 36 hours. The same patient on amikacin would receive 1050 mg every 36 hours. Round to a practical vial size, draw a nomogram level at the recommended time, and monitor renal function and trough levels throughout the course. Below a clearance of 20 mL/min, switch to traditional dosing rather than relying on this nomogram.

Why extended-interval dosing works

Aminoglycosides exhibit concentration-dependent killing: bacterial killing is maximized when the peak drug concentration is high relative to the minimum inhibitory concentration (MIC), expressed as the PK/PD target Cmax:MIC ratio (typically ≥8–10). This is fundamentally different from time-dependent antibiotics like beta-lactams, where efficacy depends on the fraction of time above the MIC.

By giving a single large dose rather than smaller divided doses, extended-interval dosing:

  • Maximizes the Cmax:MIC ratio, driving concentration-dependent killing
  • Creates a drug-free trough period that allows renal proximal tubule cells to clear accumulated drug, reducing nephrotoxicity risk
  • Exploits the post-antibiotic effect (PAE), during which bacterial regrowth is suppressed even after drug concentrations fall below the MIC

Traditional three-times-daily dosing maintains continuous drug exposure, which is counterproductive for aminoglycosides — it increases accumulation in renal cortex and cochlear tissue without improving efficacy.

The Hartford nomogram in clinical practice

The Hartford Hospital nomogram was developed to guide extended-interval dosing by providing a post-dose level check to confirm the interval is appropriate. After giving the dose:

  1. Draw a serum level at a specified time (typically 6–14 hours post-dose)
  2. Plot the level against the time on the nomogram graph
  3. The result falls into a zone labeled Q24h, Q36h, or Q48h — confirming or adjusting the chosen interval

This step is essential. The dosing interval this calculator selects from CrCl is a starting point, not a final answer. The nomogram level is what closes the loop. Some institutions use this calculation only to determine the initial dose and then rely entirely on the nomogram level for interval decisions.

Choosing the right body weight

The selection of dosing weight matters significantly because aminoglycosides distribute primarily into lean tissue, not fat:

  • Normal weight patients: use actual body weight (ABW)
  • Obese patients (typically >120% of ideal body weight or BMI >30): use adjusted body weight (ABWadj = IBW + 0.4 × [ABW − IBW])
  • Ideal body weight (IBW) estimated as: IBW (male) = 50 kg + 2.3 kg per inch above 5 feet; IBW (female) = 45.5 kg + 2.3 kg per inch above 5 feet

Using total body weight in obese patients significantly overdoses; using IBW alone underdoses.

Populations where this nomogram does not apply

Extended-interval dosing per the Hartford approach is not validated for:

  • CrCl below 20 mL/min (use traditional dosing with peak/trough monitoring)
  • Cystic fibrosis patients (altered pharmacokinetics, specialized protocols apply)
  • Pregnant patients
  • Burns patients with significantly altered volume of distribution
  • Ascites, sepsis with marked third-spacing, or other conditions causing significant distribution changes

For these populations, consult an infectious disease pharmacist and use individualized pharmacokinetic monitoring rather than a nomogram-based fixed dose.