How are initial doses calculated?

We will now discuss how initial doses of aminoglycosides can be calculated, including adjustments for kidney function and body weight.

Step One: Calculate creatinine clearance (CrCl)

As you learned previously this week, aminoglycosides are excreted renally via glomerular filtration, and therefore, it may be necessary to adjust their dosage based on renal function. Many laboratories now report a patient’s estimated glomerular filtration rate (eGFR) as a measure of renal function. However, this is calculated using population-level data rather than individual patient data and will give unreliable estimates in acute renal failure, extremes of body size and variations in skeletal muscle.

Therefore, it is recommended to use the Cockcroft-Gault equation to estimate renal function when considering initial doses of aminoglycosides. This equation is more specific to individual patients and is particularly important for use with older patients. It is used to calculate CrCl rates, a marker of renal function. It’s important to note that this method is not useful in children, as will be examined in more detail next week.

If you require a screen reader-compatible version this is available as a PDF.

Step Two: Is your patient obese?

As the Cockcroft-Gault equation shows above, weight is one of the variables. The weight used differs depending on if the patient is non-obese or obese.

• For non-obese patients, depending on local guidelines, the patient’s actual body weight (ABW) or ideal body weight (IBW) is used
• For obese patients, use an adjusted weight called the dose determining weight (DDW) is used

In week 3, we will describe in more detail how to calculate CrCl using this equation to inform aminoglycoside dosing for patients of differing weights and explain the clinical strategy for underweight and overweight patients, including those with extremes of muscle mass.

This online calculator is available to help calculate CrCl, which accounts for obesity and extremes of weight. Please read any instructions and disclaimers displayed on the calculator page. You should only use calculators that have been validated and approved by your facility in clinical practice.

Safe calculations & prescribing

The exact calculations and dosing can differ based on local guidelines, although in some locations, a more uniform approach has been adopted (e.g. in Scotland).

For patients with normal renal function, many institutions use a starting dose for gentamicin of 5-7 mg/kg once daily or 1 mg/kg twice daily in endocarditis.

Amikacin dosing has been subject to recent EUCAST discussions. In the UK, it tends to be dosed as 15 mg/kg once daily. However, in certain situations, EUCAST have suggested this may need to be 25 – 30 mg/kg.

Web-based calculators are available to calculate aminoglycoside initial dosing, and the use of certain calculators may be advised in some locations. Please pay attention to any disclaimers displayed on the calculator page. In centres where electronic prescribing is available, it is possible to embed a calculator directly into the system, acting as a safety net to ensure correct initial dosing.

Some electronic prescribing systems also allow the calculation of the initial dosage of gentamicin automatically, based on weight and height. It is also possible to automatically request the first serum level for therapeutic drug monitoring (TDM) purposes after the first dose.

In this step, we have introduced how aminoglycosides are initially dosed and how to adjust for renal function and weight. You should be aware that other considerations are also made when dosing aminoglycosides. Dosing in sepsis will be discussed next in the course, and we will return to cover additional considerations and adjustments to dosage for special patient groups in Week 3.

Check what’s available at your workplace. If aminoglycosides other than gentamicin are used routinely, are there recommendations for dosing calculations in place?

Let us know in the comments below!

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