Chapter 2: Aminoglycoside Pharmacokinetics

INTRODUCTION

The aminoglycoside class of antibiotics represents the class of drugs whose pharmacokinetics has been studied more extensively than any other. Remarkably resilient, these antibiotics continue to provide valuable weapons in the fight against infectious disease. Yet their well-known toxicities prevent their more frequent use. Clinical pharmacists are expected to serve as experts on the pharmacokinetic dosing of these drugs, and yet complex issues still lead to misunderstandings in their optimal use. In this chapter, several aspects of dosing will be presented:

• Extended interval dosing versus conventional dosing

• Traditional dosing and peak optimization

• Aminoglycoside ADRs related to trough concentrations

• Aminoglycoside dosing in acute renal failure

• Rounding serum creatinine in the elderly

• Aminoglycoside dosing in the obese patient

• Aminoglycosides used in the treatment of gram-positive endocarditis

• Aminoglycosides pharmacokinetics in pediatrics patients with cystic fibrosis

EXTENDED-INTERVAL DOSING VERSUS CONVENTIONAL DOSING

CASE 1

TJ is a 25-year-old male transferred from an outside hospital after walking in front of a moving city snowplow. X-rays taken at the outside hospital show left open pelvic fracture and a right open tibula/fibula fracture. He was intubated prior to arrival for combativeness and airway protection. Medications received prior to arrival include cefazolin 1gm via intravenous piggyback (IVPB) and fentanyl 150 mcg slow IV push. The orthopedics team is consulted in the emergency department and wants to add gentamicin for additional coverage of the open fracture.

Vital Signs:

Labs:

What is your recommendation for starting gentamicin?

The first step to approaching an aminoglycoside patient is to calculate the weight to be used for dosing. Convert the patient's actual body weight (ABW) from pounds (lb) to kilograms (kg) and determine the ideal body weight (IBW). Utilization of a calculated dosing weight may be necessary if the actual body weight is greater than 20 percent of the ideal body weight. This concept will be discussed in detail in another section.

Because ABW <1.2(IBW), actual body weight will be used.

The next step is to determine the patient's renal function, which is most often done by estimating their creatinine clearance (CrCl), utilizing the Cockcroft-Gault equation.¹ Estimating CrCl will assist in determining whether the patient is a candidate for extended interval dosing versus conventional dosing and for selecting the appropriate dosing schedule.

Once the determination to use an aminoglycoside has been made, the pharmacist can assist with the selection of the regimen.

Three common methods are used in designing an effective and safe aminoglycoside regimen: conventional or traditional dosing (CD), individualized dosing, and extended interval dosing (EID). Conventional dosing involves giving the total daily dose of the aminoglycoside divided throughout the day, typically every 8 to 12 hours in patients with good ...