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Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial

Jan De Waele (UGent) , Sofie Carrette (UGent) , Mieke Carlier (UGent) , Veronique Stove (UGent) , Jerina Boelens (UGent) , Geert Claeys (UGent) , Isabel Leroux-Roels (UGent) , Eric Hoste (UGent) , Pieter Depuydt (UGent) , Johan Decruyenaere (UGent) , et al.
(2014) INTENSIVE CARE MEDICINE. 40(3). p.380-387
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Abstract
Purpose: There is variability in the pharmacokinetics (PK) of antibiotics (AB) in critically ill patients. Therapeutic drug monitoring (TDM) could overcome this variability and increase PK target attainment. The objective of this study was to analyse the effect of a dose-adaption strategy based on daily TDM on target attainment. Methods: This was a prospective, partially blinded, and randomised controlled trial in patients with normal kidney function treated with meropenem (MEM) or piperacillin/tazobactam (PTZ). The intervention group underwent daily TDM, with dose adjustment when necessary. The predefined PK/pharmacodynamic (PK/PD) target was 100 % fT(> 4MIC) [percentage of time during a dosing interval that the free (f) drug concentration exceeded 4 times the MIC]. The control group received conventional treatment. The primary endpoint was the proportion of patients that reached 100 % fT(> 4MIC) and 100 % fT(> MIC) at 72 h. Results: Forty-one patients (median age 56 years) were included in the study. Pneumonia was the primary infectious diagnosis. At baseline, 100 % fT(> 4MIC) was achieved in 21 % of the PTZ patients and in none of the MEM patients; 100 % fT(> MIC) was achieved in 71 % of the PTZ patients and 46 % of the MEM patients. Of the patients in the intervention group, 76 % needed dose adaptation, and five required an additional increase. At 72 h, target attainment rates for 100 % fT(> 4MIC) and 100 % fT(> MIC) were higher in the intervention group: 58 vs. 16 %, p = 0.007 and 95 vs. 68 %, p = 0.045, respectively. Conclusions: Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing.
Keywords
Pharmacodynamics, Therapeutic drug monitoring, Pharmacokinetics, beta-Lactam antibiotics, Critical care, CRITICALLY-ILL PATIENTS, AUGMENTED RENAL CLEARANCE, BETA-LACTAM ANTIBIOTICS, INTENSIVE-CARE-UNIT, SEVERE SEPSIS, SEPTIC SHOCK, PSEUDOMONAS-AERUGINOSA, PHARMACOKINETICS, PHARMACODYNAMICS, INFUSION

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MLA
De Waele, Jan, Sofie Carrette, Mieke Carlier, et al. “Therapeutic Drug Monitoring-based Dose Optimisation of Piperacillin and Meropenem: a Randomised Controlled Trial.” INTENSIVE CARE MEDICINE 40.3 (2014): 380–387. Print.
APA
De Waele, Jan, Carrette, S., Carlier, M., Stove, V., Boelens, J., Claeys, G., Leroux-Roels, I., et al. (2014). Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial. INTENSIVE CARE MEDICINE, 40(3), 380–387.
Chicago author-date
De Waele, Jan, Sofie Carrette, Mieke Carlier, Veronique Stove, Jerina Boelens, Geert Claeys, Isabel Leroux-Roels, et al. 2014. “Therapeutic Drug Monitoring-based Dose Optimisation of Piperacillin and Meropenem: a Randomised Controlled Trial.” Intensive Care Medicine 40 (3): 380–387.
Chicago author-date (all authors)
De Waele, Jan, Sofie Carrette, Mieke Carlier, Veronique Stove, Jerina Boelens, Geert Claeys, Isabel Leroux-Roels, Eric Hoste, Pieter Depuydt, Johan Decruyenaere, and Alain Verstraete. 2014. “Therapeutic Drug Monitoring-based Dose Optimisation of Piperacillin and Meropenem: a Randomised Controlled Trial.” Intensive Care Medicine 40 (3): 380–387.
Vancouver
1.
De Waele J, Carrette S, Carlier M, Stove V, Boelens J, Claeys G, et al. Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial. INTENSIVE CARE MEDICINE. 2014;40(3):380–7.
IEEE
[1]
J. De Waele et al., “Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial,” INTENSIVE CARE MEDICINE, vol. 40, no. 3, pp. 380–387, 2014.
@article{5648047,
  abstract     = {Purpose: There is variability in the pharmacokinetics (PK) of antibiotics (AB) in critically ill patients. Therapeutic drug monitoring (TDM) could overcome this variability and increase PK target attainment. The objective of this study was to analyse the effect of a dose-adaption strategy based on daily TDM on target attainment.
Methods: This was a prospective, partially blinded, and randomised controlled trial in patients with normal kidney function treated with meropenem (MEM) or piperacillin/tazobactam (PTZ). The intervention group underwent daily TDM, with dose adjustment when necessary. The predefined PK/pharmacodynamic (PK/PD) target was 100 % fT(> 4MIC) [percentage of time during a dosing interval that the free (f) drug concentration exceeded 4 times the MIC]. The control group received conventional treatment. The primary endpoint was the proportion of patients that reached 100 % fT(> 4MIC) and 100 % fT(> MIC) at 72 h.
Results: Forty-one patients (median age 56 years) were included in the study. Pneumonia was the primary infectious diagnosis. At baseline, 100 % fT(> 4MIC) was achieved in 21 % of the PTZ patients and in none of the MEM patients; 100 % fT(> MIC) was achieved in 71 % of the PTZ patients and 46 % of the MEM patients. Of the patients in the intervention group, 76 % needed dose adaptation, and five required an additional increase. At 72 h, target attainment rates for 100 % fT(> 4MIC) and 100 % fT(> MIC) were higher in the intervention group: 58 vs. 16 %, p = 0.007 and 95 vs. 68 %, p = 0.045, respectively.
Conclusions: Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing.},
  author       = {De Waele, Jan and Carrette, Sofie and Carlier, Mieke and Stove, Veronique and Boelens, Jerina and Claeys, Geert and Leroux-Roels, Isabel and Hoste, Eric and Depuydt, Pieter and Decruyenaere, Johan and Verstraete, Alain},
  issn         = {0342-4642},
  journal      = {INTENSIVE CARE MEDICINE},
  keywords     = {Pharmacodynamics,Therapeutic drug monitoring,Pharmacokinetics,beta-Lactam antibiotics,Critical care,CRITICALLY-ILL PATIENTS,AUGMENTED RENAL CLEARANCE,BETA-LACTAM ANTIBIOTICS,INTENSIVE-CARE-UNIT,SEVERE SEPSIS,SEPTIC SHOCK,PSEUDOMONAS-AERUGINOSA,PHARMACOKINETICS,PHARMACODYNAMICS,INFUSION},
  language     = {eng},
  number       = {3},
  pages        = {380--387},
  title        = {Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial},
  url          = {http://dx.doi.org/10.1007/s00134-013-3187-2},
  volume       = {40},
  year         = {2014},
}

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