Giuseppe
Emeritus
[Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]
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Dosing nomograms for attaining optimum concentrations of meropenem by continuous infusion in critically ill patients for severe Gram-negative infections: a PK/PD based approach
Federico Pea 1,*, Pierluigi Viale 2, Piergiorgio Cojutti 1 and Mario Furlanut 1
Author Affiliations: <SUP>1</SUP>Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Department of Experimental and Clinical Medicine, Medical School, University of Udine, Udine, Italy <SUP>2</SUP>Clinic of Infectious Diseases, Department of Internal Medicine, Geriatrics and Nephrologic Diseases, University of Bologna, Italy
ABSTRACT
Objectives.
The worrisome increase in Gram-negatives with borderline-susceptibility to carbapenems and of carbapenemase producing Enterobacteriaceae has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL<SUB>Cr</SUB>) estimates for use in daily clinical practice to target the steady-state concentrations (C<SUB>ss</SUB>s) of meropenem during continuous infusion at 8-16 mg/L (after the administration of an initial loading dose of 1-2 g over 30 min).
Methods.
The correlation between meropenem clearance (CL<SUB>m</SUB>) and CL<SUB>Cr</SUB> was retrospectively assessed in a cohort of critically ill patients (group 1, n=67) to create a formula for dosage calculation to target C<SUB>ss</SUB>. The performance of this formula was validated in a similar cohort (group 2, n=56) by comparison of the observed and the predicted C<SUB>ss</SUB>s.
Results.
A significant relationship between CL<SUB>m</SUB> and CL<SUB>Cr</SUB> was observed in group 1 (r=0.72, P<0.001). The application of the formula to meropenem dosing in group 2 {infusion rate (g/24 h) = [0.078 ? CL<SUB>Cr</SUB> (mL/min) + 2.85] ? target C<SUB>ss</SUB> ? (24/1,000)} led to a significant correlation between the observed and the predicted C<SUB>ss</SUB>s (r=0.92, P<0.001).
Conclusion.
Dosing nomograms based on CL<SUB>Cr</SUB> were created to target the meropenem C<SUB>ss</SUB> at 8, 12 and 16 mg/L in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline-susceptible pathogens or even of carbapenemase-producers and/or of pathophysiological conditions which may enhance meropenem clearance.
FOOTNOTES
*Corresponding author. Mailing address: Institute of Clinical Pharmacology & Toxicology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Department of Experimental and Clinical Medicine, Medical School, University of Udine, Udine, Italy, P.le S. Maria della Misericordia 3, 33100 Udine, Italy. Phone: +39 0432 559833. Fax: +39 0432 559819. E-mail: pea.federico@aoud.sanita.fvg.it
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
-Author Affiliations: <SUP>1</SUP>Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Department of Experimental and Clinical Medicine, Medical School, University of Udine, Udine, Italy <SUP>2</SUP>Clinic of Infectious Diseases, Department of Internal Medicine, Geriatrics and Nephrologic Diseases, University of Bologna, Italy
ABSTRACT
Objectives.
The worrisome increase in Gram-negatives with borderline-susceptibility to carbapenems and of carbapenemase producing Enterobacteriaceae has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL<SUB>Cr</SUB>) estimates for use in daily clinical practice to target the steady-state concentrations (C<SUB>ss</SUB>s) of meropenem during continuous infusion at 8-16 mg/L (after the administration of an initial loading dose of 1-2 g over 30 min).
Methods.
The correlation between meropenem clearance (CL<SUB>m</SUB>) and CL<SUB>Cr</SUB> was retrospectively assessed in a cohort of critically ill patients (group 1, n=67) to create a formula for dosage calculation to target C<SUB>ss</SUB>. The performance of this formula was validated in a similar cohort (group 2, n=56) by comparison of the observed and the predicted C<SUB>ss</SUB>s.
Results.
A significant relationship between CL<SUB>m</SUB> and CL<SUB>Cr</SUB> was observed in group 1 (r=0.72, P<0.001). The application of the formula to meropenem dosing in group 2 {infusion rate (g/24 h) = [0.078 ? CL<SUB>Cr</SUB> (mL/min) + 2.85] ? target C<SUB>ss</SUB> ? (24/1,000)} led to a significant correlation between the observed and the predicted C<SUB>ss</SUB>s (r=0.92, P<0.001).
Conclusion.
Dosing nomograms based on CL<SUB>Cr</SUB> were created to target the meropenem C<SUB>ss</SUB> at 8, 12 and 16 mg/L in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline-susceptible pathogens or even of carbapenemase-producers and/or of pathophysiological conditions which may enhance meropenem clearance.
FOOTNOTES
*Corresponding author. Mailing address: Institute of Clinical Pharmacology & Toxicology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Department of Experimental and Clinical Medicine, Medical School, University of Udine, Udine, Italy, P.le S. Maria della Misericordia 3, 33100 Udine, Italy. Phone: +39 0432 559833. Fax: +39 0432 559819. E-mail: pea.federico@aoud.sanita.fvg.it
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
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