Continuous Infusion of Piperacillin/Tazobactam and Meropenem in ICU Patients Without Renal Dysfunction: Are Patients at Risk of Underexposure?
Background and Objectives Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment. Results We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02–0.12) mg/l; piperacillin: 3 (1–4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100%f$ C_{ss≥1xMIC} $, 100%f$ C_{ss≥4xMIC} $ and 100%f$ C_{ss ≥ 8xMIC} $, respectively) were: 100%, 96.15%, 96.15% (meropenem) and 95.56%, 91.11%, 62.22% (piperacillin) for actual MIC; 98.11%, 71.70%, 47.17% (meropenem, MIC 2 mg/l), 95.83%, 44.79%, 6.25% (piperacillin, MIC 8 mg/l), 83.33%, 6.25%, 1.04% (piperacillin, MIC 16 mg/l) for EUCAST breakpoint of Enterobacteriaceae spp. and Pseudomonas spp. Multivariable linear analysis identified creatinine clearance (CrCL) as a predictive factor of free antibiotic concentrations (f$ C_{ss} $) of both therapies (meropenem [β = − 0.01 (95% CI − 0.02 to − 0.0; p = 0.043)] and piperacillin [β = − 0.01 (95% CI − 0.02 to 0.01, p < 0.001)]). Neurocritical status was associated with lower piperacillin f$ C_{ss} $ [β = − 0.36 (95% CI − 0.61 to − 0.11; p = 0.005)]. Conclusion Standard total daily dose of meropenem allowed achieving pharmacokinetic/pharmacodynamic target attainments in ICU patients without renal dysfunction. Higher doses of piperacillin/tazobactam would be needed to cover microorganisms with MIC > 8 mg/l. CrCL was the most powerful factor predictive of f$ C_{ss} $ in both therapies..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:46 |
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| Enthalten in: |
European journal of drug metabolism and pharmacokinetics - 46(2021), 4 vom: 15. Juni, Seite 527-538 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Esteve-Pitarch, Erika [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021 |
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| doi: |
10.1007/s13318-021-00694-0 |
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OLC2126799409 |
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| 245 | 1 | 0 | |a Continuous Infusion of Piperacillin/Tazobactam and Meropenem in ICU Patients Without Renal Dysfunction: Are Patients at Risk of Underexposure? |
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| 520 | |a Background and Objectives Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment. Results We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02–0.12) mg/l; piperacillin: 3 (1–4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100%f$ C_{ss≥1xMIC} $, 100%f$ C_{ss≥4xMIC} $ and 100%f$ C_{ss ≥ 8xMIC} $, respectively) were: 100%, 96.15%, 96.15% (meropenem) and 95.56%, 91.11%, 62.22% (piperacillin) for actual MIC; 98.11%, 71.70%, 47.17% (meropenem, MIC 2 mg/l), 95.83%, 44.79%, 6.25% (piperacillin, MIC 8 mg/l), 83.33%, 6.25%, 1.04% (piperacillin, MIC 16 mg/l) for EUCAST breakpoint of Enterobacteriaceae spp. and Pseudomonas spp. Multivariable linear analysis identified creatinine clearance (CrCL) as a predictive factor of free antibiotic concentrations (f$ C_{ss} $) of both therapies (meropenem [β = − 0.01 (95% CI − 0.02 to − 0.0; p = 0.043)] and piperacillin [β = − 0.01 (95% CI − 0.02 to 0.01, p < 0.001)]). Neurocritical status was associated with lower piperacillin f$ C_{ss} $ [β = − 0.36 (95% CI − 0.61 to − 0.11; p = 0.005)]. Conclusion Standard total daily dose of meropenem allowed achieving pharmacokinetic/pharmacodynamic target attainments in ICU patients without renal dysfunction. Higher doses of piperacillin/tazobactam would be needed to cover microorganisms with MIC > 8 mg/l. CrCL was the most powerful factor predictive of f$ C_{ss} $ in both therapies. | ||
| 700 | 1 | |a Gumucio-Sanguino, Víctor Daniel |4 aut | |
| 700 | 1 | |a Cobo-Sacristán, Sara |4 aut | |
| 700 | 1 | |a Shaw, Evelyn |4 aut | |
| 700 | 1 | |a Maisterra-Santos, Kristel |4 aut | |
| 700 | 1 | |a Sabater-Riera, Joan |4 aut | |
| 700 | 1 | |a Pérez-Fernandez, Xosé L. |4 aut | |
| 700 | 1 | |a Rigo-Bonnin, Raül |4 aut | |
| 700 | 1 | |a Tubau-Quintano, Fe |4 aut | |
| 700 | 1 | |a Carratalà, Jordi |4 aut | |
| 700 | 1 | |a Colom-Codina, Helena |4 aut | |
| 700 | 1 | |a Padullés-Zamora, Ariadna |4 aut | |
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