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Role for Dual Individualization with Cefmenoxime

  • Author Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Jerome J. Schentag
    Correspondence
    Requests for reprints should be addressed to Dr. Jerome J. Schentag, Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, 3 Gates Circle, Buffalo, New York 14209.
    Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Affiliations
    Buffalo, New York
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  • Author Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Ian L. Smith
    Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Affiliations
    Buffalo, New York
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  • Author Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Douglas J. Swanson
    Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
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    Buffalo, New York
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  • Author Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Carlo DeAngelis
    Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
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    Buffalo, New York
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  • Author Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Joseph E. Fracasso
    Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
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    Buffalo, New York
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  • Author Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Andras Vari
    Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
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    Buffalo, New York
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  • Author Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    John W. Vance
    Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
    Affiliations
    Buffalo, New York
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  • Author Footnotes
    b From the Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, and the Department of Medicine and the Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York.
      This paper is only available as a PDF. To read, Please Download here.
      Cefmenoxime concentration/effect relationships were retrospectively explored for gram-negative bacteria isolated from 14 critical care patients treated for nosocomial pneumonia. The effects of cefmenoxime concentrations on in vitro growth kinetics of 21 isolated pathogens were studied using the Abbott MS-2 Research System, from which a dynamic response concentration was derived. Serum pharmacokinetic profiles were obtained in each patient. These data were used to calculate the in vivo total area under the curve over dynamic response concentration and the time that cefmenoxime concentrations exceeded the dynamic response concentration for each bacteria. The same determinations were made in 18 patients prospectively treated, except that dosage was optimized on the basis of previous mathematical relations to achieve bacterial eradication in four days. This method of dosage optimization is termed dual individualization. Serial cultures of infected tissues were evaluated to determine the number of days to the eradication of bacteria, and the pharmacokinetic and pharmacodynamic variables were used to describe the bacteriologic response of the original pathogen isolated in pretreatment culture. Bacterial eradication rates could be described from cefmenoxime pharmacokinetics in the patient and from the relation between concentration and bacterial inhibition. Patients who were prospectively treated using these retrospectively derived relationships had a predictable day of bacterial eradication. This, in turn, was associated with a shorter duration of treatment (p < 0.05). The success of prospective dual individualization is encouraging and suggests that more precise optimization of antibiotic dosage can yield a predictable rate of bacterial eradication from the infection site.
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      1. Schentag JJ, Swanson DJ, Smith IL: Dual individualization: antibiotic dosage calculation from the integration of in vitro pharmacodynamics and in vivo pharmacokinetics. J Antimicrob Chemother (in press).

      2. Schentag JJ, Swanson DJ, DeAngelis C, Reitberg DP, Cumbo TJ, Smith IL: Cefmenoxime concentration/effect relationships derived from treatment of nosocomial pneumonia: determinants of bacterial eradication. Clin Pharmacol Ther (in press).

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