Aminoglycoside Peak/Trough Interpretations

This past month, I had the pleasure to co-precept a pharmacy resident on an Antimicrobial Stewardship (AMS) rotation. Being a (mostly) outpatient HIV pharmacist for the last 10 months, I was both excited and nervous. What aspects of AMS could I cover from an HIV/outpatient perspective?

Oh, how I surprised myself.

The more I thought about it, the more I realized that HIV is all about AMS! In HIV care, we are constantly trying to prevent:

• New cases of HIV (pre-and post-exposure prophylaxis)
• Increased spread of HIV (control viral loads with appropriate antiretroviral treatment regimens)
• Opportunistic infections
• Sexually transmitted diseases
• Resistance (obtain viral suppression and enforce adherence)

After realizing the above, I was ecstatic to dip my toe into a precepting role!

The resident mentioned that one of their goals was to increase confidence with aminoglycoside pharmacokinetics (PK). Amikacin is an aminoglycoside used in disseminated mycobacterium infections and other opportunistic infections that can plague patients living with HIV. Through my discussions with the resident, I created some useful visuals that I figured would be beneficial to also share here on RxTeach!

For instance, when do you know to change the dose or the interval of a dosing regimen? How do you apply all the calculations from pharmacy school to a real clinical scenario? Aren't there online software and nomograms for that now?

This is what I think is intriguing about these specialized patient populations: the more complicated the patient, the less that patient fits into these nomograms, data sets, and software programs. THIS is where pharmacists shine: when you need to pull out those dusty PK equations!

What this post IS

• A quick refresher on a few PK equations and when to use them
• A simple guide/visual to appropriately assess aminoglycoside (primarily amikacin) peak and trough levels and the following changes to either the dose or interval
• Created using this the Stanford Health Care Aminoglycoside Dosing Guidelines

What this post IS NOT

• A comprehensive guide for all PK (for instance, we are NOT talking about vancomycin today)
• An end-all-be-all to all things PK
• A refresher on the Urban-Craig and Hartford nomograms for gentamicin/tobramycin
  • If you would like this, might I suggest this tl;dr pharmacy article
• A review of complicated infectious diseases and guidelines recommend treatment options

All right! It is time to jump into the real content.

What to do with a peak and trough

A peak is the maximum concentration of a drug after a dose is given.

A trough is the minimum concentration of a drug right before the next dose is given.

The graphic below provides a great visual for these terms.

Aminoglycosides (gentamicin, tobramycin, streptomycin, amikacin, etc.), are considered concentration-dependent. This means a specific concentration of aminoglycoside must be achieved to kill infectious bacteria. It does not matter how long the concentration is above the minimum effective concentration (mic): this is time-dependent killing (beta-lactams, for example).

Aminoglycosides are known for ototoxicity and nephrotoxicity when dosed too aggressively. This is where the goal peak range in the treatment guidelines comes into play. The goal peak range will be below the toxic concentration limit. It is important to avoid supratherapeutic peaks to ensure safe and effective use of aminoglycosides.

Specific to aminoglycosides, the peak is drawn once at steady-state (typically after 3-4 doses). The peak is collected 30 minutes after the infusion ends. For most doses, the infusion will take 30 minutes. If the amikacin dose is >15 mg/kg, the dose will be infused over 60 minutes.

The trough is collected right before the next dose is infused, as the nurse is already at the bedside to hang the dose and can collect a blood sample at the same time.

How to calculate a true peak and trough

1. Find elimination rate constant (Ke)
2. Calculate true max concentration (Cmax_actual)
3. Calculate true min concentration (Cmin_actual)

Finding Ke