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Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharma...
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| Zeitschriftentitel: | Antimicrobial Agents and Chemotherapy |
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| Personen und Körperschaften: | , , , |
| In: | Antimicrobial Agents and Chemotherapy, 56, 2012, 12, S. 6343-6348 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>ABSTRACT</jats:title> <jats:p> The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> 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 <jats:sub>Cr</jats:sub> ) estimates for use in daily clinical practice to target the steady-state concentrations ( <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CL <jats:sub>m</jats:sub> ) and CL <jats:sub>Cr</jats:sub> was retrospectively assessed in a cohort of critically ill patients (group 1, <jats:italic>n</jats:italic> = 67) to create a formula for dosage calculation to target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> . The performance of this formula was validated in a similar cohort (group 2, <jats:italic>n</jats:italic> = 56) by comparison of the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s. A significant relationship between CL <jats:sub>m</jats:sub> and CL <jats:sub>Cr</jats:sub> was observed in group 1 ( <jats:italic>r</jats:italic> = 0.72, <jats:italic>P</jats:italic> < 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CL <jats:sub>Cr</jats:sub> (ml/min) + 2.85] × target <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> × (24/1,000), led to a significant correlation between the observed and the predicted <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> s ( <jats:italic>r</jats:italic> = 0.92, <jats:italic>P</jats:italic> < 0.001). Dosing nomograms based on CL <jats:sub>Cr</jats:sub> were created to target the meropenem <jats:italic>C</jats:italic> <jats:sub>ss</jats:sub> at 8, 12, and 16 mg/liter 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. </jats:p> |
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| Umfang: | 6343-6348 |
| ISSN: |
0066-4804
1098-6596 |
| DOI: | 10.1128/aac.01291-12 |