Pharmacokinetic dosing of aminoglycosides: A controlled trial

Carmi Bartal, Abraham Danon, Francisc Schlaeffer, Klaris Reisenberg, Michael Alkan, Rosa Smoliakov, Aviel Sidi, Yaniv Almog

    Research output: Contribution to journalArticlepeer-review

    128 Scopus citations

    Abstract

    PURPOSE: To evaluate whether individualized pharmacokinetic dosing of aminoglycosides can reduce nephrotoxicity and improve the outcome of patients with gram-negative sepsis. METHODS: We conducted a prospective controlled trial at a tertiary care university hospital. Eighty-one patients with suspected or documented gram-negative infections were enrolled. All were treated with either gentamicin or amikacin, according to clinical judgement. Patients were allocated to one of two groups based on the last digit (odd/even) of their identification number. In the study group (pharmacokinetic dosing) of 43 patients, plasma aminoglycoside levels were determined 1 hour after initiation of drug infusion and 8 to 16 hours later to estimate the elimination half-life and volume of distribution, from which the subsequent dosage schedule was calculated. Target peak plasma levels were 20 μg/mL for gentamicin and 60 μg/mL for amikacin. Target trough levels were <1 μg/mL for both drugs. The control group (fixed once-daily dosing) consisted of 38 patients who were prescribed single daily doses of gentamicin or amikacin. The primary endpoints were renal toxicity (≥25% increase in serum creatinine level or a serum creatinine level ≥1.4 mg/dL) and 28-day mortality. RESULTS: The two study groups were similar in age, sex, indications for therapy, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and clinical assessment at baseline. Although the pharmacokinetic group received significantly greater doses of aminoglycosides than did the once-daily group, the incidence of nephrotoxicity was significantly lower in the pharmacokinetic group (5% [2/43] vs. 21% [8/38], P = 0.03). There was no statistically significant difference in 28-day mortality (27% [12/43] vs. 22% [8/38], P = 0.3). CONCLUSION: These results suggest that individualized pharmacokinetic dosing of aminoglycosides reduces the incidence of nephrotoxicity and allows the use of greater doses of aminoglycosides.

    Original languageEnglish
    Pages (from-to)194-198
    Number of pages5
    JournalAmerican Journal of Medicine
    Volume114
    Issue number3
    DOIs
    StatePublished - 15 Feb 2003

    ASJC Scopus subject areas

    • General Medicine

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