A 38 y/o, 65 kg male patient being treating with IV gentamicin for a gram negative, possibly aspiration, pneumonia. His dosing regimen is 120 mg IVPB every 8 hours. His renal function is normal (CrCl ~ 85 ml/min) and has no other underlying medical conditions. His other meds include clindamycin 900mg IVPB every 8 hours.

A peak and trough level was drawn 1-2 days ago around his 3rd dose of gentamicin. The peak was 8.1 mcg/mL and his trough was 1.1 mcg/mL. His renal function hasn’t changed and the patient appears to be getting better. The medical student wants to redraw the peak and trough levels.

Do you agree or not? Why or why not?

** THANKS to Dr Annabel Schumaker, Pharm.D. for her help with this Pearl. **

Probably not. If the levels were drawn correctly and there’s no change in renal function and no worsening of the infection (i.e. patient is improving), what advantage is there to redrawing the levels? Little, if any. On the other hand, if the patient’s renal function had worsened, or his clinical condition had turned south, or he’d started to develop a significant amount of ascites or third space fluids or had become septic, then repeating the levels and adjusting the dosing regimen would probably have been a good idea.

Some info on aminoglycosides and their monitoring:

Peak levels during a traditional every 8 hour IV regimen should be drawn around the third dose of the regimen to approximate steady state. Draw the trough immediately before the dose and the peak 30 minutes after a 30-60 minute infusion. For IM dosing, draw the trough right before the dose and the peak 60 minutes after the IM injection. Be SURE to annotate the time the dose was given and the time the level(s) were drawn on the lab slip. With this information, you can account for the time differences and calculate accordingly. This should apply to gentamicin, tobramycin, and amikacin.

Although toxicity is normally associated with elevated levels, toxicity CAN occur even with normal levels. Monitoring of serum creatinine 2-3 times a week during therapy is a reasonable way to watch for nephrotoxicity. Our WHMC nomogram states “An increase in Cr .0.4mg/dl may indicate aminoglycoside toxicity.”

For daily dosing  (often referred to as high dose or consolidated dosing) – peak levels are usually for academic interest only. This dosing regimen is meant to achieve peak levels of ~ 25 mcg/mL, much higher than the traditional dosing and troughs of less than 1 mcg/mL. Getting peak levels in this instance offers little (if any) valuable clinical information, generates a bunch of warnings and alert levels, and generates additional cost. For daily dosing of aminoglycosides, a random level drawn between 6 and 14 hours after the dose can be plotted on a nomogram created by Nicolau D and associates.  Depending on where the level falls, the nomogram will help you determine whether to extend the dosing interval beyond 24 hours. The same dose is given but the interval is extended. There are exclusion criteria for some patient’s and disease states. These include but are not limited:

CF, burn >20% BSA pts, enterococcal endocarditis, ESRD on dialysis, pregnancy. These conditions either have significantly expanded volumes of distribution OR supranormal clearance of the drugs.

    Normal peak levels:

Gentamicin/tobramycin

        (every 8 hour dosing)        (every 24 hour dosing)
        Peaks – 4 – 10 mcg/mL    Peaks > ~ 20-25 mcg/mL
        Amikacin
        (every 8 hour dosing)        (every 24 hours)
        Peaks – 20-30 mcg/mL    Peaks > ~ 40-60 mcg/mL

        Normal trough levels:

Gentamicin/tobramycin

        (every 8 hour dosing)        (every 24 hour dosing)
        Troughs – < 2 mcg/mL        Troughs < 1-2 mcg/mL
        Amikacin
        (every 8 hour dosing)        (every 24 hours)
        Troughs – < 8 mcg/mL        Troughs < 8 mcg/mL

Elevated trough levels have been associated with both nephro and ototoxicity (auditory and vestibular). These can be irreversible. To clarify, nephrotoxicity is usually reversible over several weeks, but the ototoxicity is often is NOT reversible REMEMBER when getting and assessing serum levels, WHEN they were drawn in relation to the dose is EXTREMELY important. You need to do a little detective work to find this information out because it can cause significant differences in your calculations and any dosing changes made in your patient. For example, if the peak is drawn several hours after the end of the infusion instead of one hour later, the true peak serum level is actually HIGHER than the value obtained. Another thing to remember about drawing serum levels of drugs is the cost (nursing time, lab cost, etc., and the exposure of the patient to a needlestick, blood loss, etc.). Each time you order a level it cost the lab to analyze it, the nurse to draw it, and someone to read it and make a decision on what to do with it. See below for WHMC local costs for the various serum levels:

Gentamicin peak/trough: $5.25
Tobramicin peak/trough: $4.73
Amikacin peak/trough: $4.02

REFERENCES:

*    Nicolau DP, Freeman CD, Belliveau PP et al: Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother 1995; 39(3):650-655.

This Pearl is meant for academic and educational purposes only. This Pearl is meant to raise important points regarding the safe and cost-effective pharmacotherapy of patients. It is not meant to be the definitive reference for the treatment or prophylaxis of various diseases. Although every effort is taken to ensure this Pearl is correct and factual, errors may occur. The Pharmacoeconomic Center assumes no liability for incorrect information or harm that may occur from the use of the information included in this Pearl.