What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?

The objectives of this study were to determine the effects of obesity on unbound trough concentrations and on the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets of piperacillin and meropenem in critically ill patients. This study retrospectively analysed therapeutic-drug-monitorin...

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Main Authors: Alobaid, Abdulaziz S., Brinkmann, Alexander, Frey, Otto R., Roehr, Anka C., Luque, Sonia, Grau, Santiago, Wong , Gloria, Abdul Aziz, Mohd. Hafiz, Roberts, Michael S., Lipman, Jeffrey, Roberts, Jason A.
Format: Article
Language:English
Published: Oxford Journals 2015
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Online Access:http://irep.iium.edu.my/46717/
http://irep.iium.edu.my/46717/1/J._Antimicrob._Chemother.-2015-Alobaid-jac-dkv412.pdf
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author Alobaid, Abdulaziz S.
Brinkmann, Alexander
Frey, Otto R.
Roehr, Anka C.
Luque, Sonia
Grau, Santiago
Wong , Gloria
Abdul Aziz, Mohd. Hafiz
Roberts, Michael S.
Lipman, Jeffrey
Roberts, Jason A.
author_facet Alobaid, Abdulaziz S.
Brinkmann, Alexander
Frey, Otto R.
Roehr, Anka C.
Luque, Sonia
Grau, Santiago
Wong , Gloria
Abdul Aziz, Mohd. Hafiz
Roberts, Michael S.
Lipman, Jeffrey
Roberts, Jason A.
author_sort Alobaid, Abdulaziz S.
building IIUM Repository
collection Online Access
description The objectives of this study were to determine the effects of obesity on unbound trough concentrations and on the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets of piperacillin and meropenem in critically ill patients. This study retrospectively analysed therapeutic-drug-monitoring data from ICU databases in Australia, Germany and Spain, as well as from a large PK study. The presence of obesity was defined as a BMI ≥30 kg/m2, and patients were also categorized based on level of renal function. The presence of obesity was compared with unbound piperacillin and meropenem trough concentrations. We also used logistic regression to describe factors associated with the achievement of the PK/PD targets, an unbound concentration maintained above the MIC breakpoint (100% fT>MIC and 100% fT>4×MIC) of Pseudomonas aeruginosa. In all, 1400 patients were eligible for inclusion in the study. The median age and weight were 67 years (IQR 52-76 years) and 79 kg (69-90 kg), respectively, and 65% of participants were male. Significantly lower median piperacillin trough concentrations [29.4 mg/L (IQR 17.0-58.0 mg/L)] were found in obese patients compared with non-obese patients [42.0 mg/L (21.5-73.5 mg/L)] (P = 0.001). There was no difference for meropenem trough concentrations [obese 10.3 mg/L (IQR 4.8-16.0 mg/L) versus non-obese 11.0 mg/L (4.3-18.5 mg/L); P = 0.296]. Using logistic regression, we found that the presence of obesity was not associated with achievement of 100% fT>MIC, but the use of prolonged infusion, a creatinine clearance ≤100 mL/min, increasing age and female gender were for various PK/PD targets for both piperacillin and meropenem (P < 0.05). This large dataset has shown that the presence of obesity in critically ill patients may affect piperacillin, but not meropenem, unbound trough concentrations.
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spelling iium-467172016-02-03T04:31:08Z http://irep.iium.edu.my/46717/ What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients? Alobaid, Abdulaziz S. Brinkmann, Alexander Frey, Otto R. Roehr, Anka C. Luque, Sonia Grau, Santiago Wong , Gloria Abdul Aziz, Mohd. Hafiz Roberts, Michael S. Lipman, Jeffrey Roberts, Jason A. QR Microbiology RM Therapeutics. Pharmacology RM300 Drugs and their action RS Pharmacy and materia medica The objectives of this study were to determine the effects of obesity on unbound trough concentrations and on the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets of piperacillin and meropenem in critically ill patients. This study retrospectively analysed therapeutic-drug-monitoring data from ICU databases in Australia, Germany and Spain, as well as from a large PK study. The presence of obesity was defined as a BMI ≥30 kg/m2, and patients were also categorized based on level of renal function. The presence of obesity was compared with unbound piperacillin and meropenem trough concentrations. We also used logistic regression to describe factors associated with the achievement of the PK/PD targets, an unbound concentration maintained above the MIC breakpoint (100% fT>MIC and 100% fT>4×MIC) of Pseudomonas aeruginosa. In all, 1400 patients were eligible for inclusion in the study. The median age and weight were 67 years (IQR 52-76 years) and 79 kg (69-90 kg), respectively, and 65% of participants were male. Significantly lower median piperacillin trough concentrations [29.4 mg/L (IQR 17.0-58.0 mg/L)] were found in obese patients compared with non-obese patients [42.0 mg/L (21.5-73.5 mg/L)] (P = 0.001). There was no difference for meropenem trough concentrations [obese 10.3 mg/L (IQR 4.8-16.0 mg/L) versus non-obese 11.0 mg/L (4.3-18.5 mg/L); P = 0.296]. Using logistic regression, we found that the presence of obesity was not associated with achievement of 100% fT>MIC, but the use of prolonged infusion, a creatinine clearance ≤100 mL/min, increasing age and female gender were for various PK/PD targets for both piperacillin and meropenem (P < 0.05). This large dataset has shown that the presence of obesity in critically ill patients may affect piperacillin, but not meropenem, unbound trough concentrations. Oxford Journals 2015 Article PeerReviewed application/pdf en http://irep.iium.edu.my/46717/1/J._Antimicrob._Chemother.-2015-Alobaid-jac-dkv412.pdf Alobaid, Abdulaziz S. and Brinkmann, Alexander and Frey, Otto R. and Roehr, Anka C. and Luque, Sonia and Grau, Santiago and Wong , Gloria and Abdul Aziz, Mohd. Hafiz and Roberts, Michael S. and Lipman, Jeffrey and Roberts, Jason A. (2015) What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients? Journal of Antimicrobial Chemotherapy, 71 (2). pp. 1-7. ISSN 0305-7453 http://jac.oxfordjournals.org/content/early/2015/12/24/jac.dkv412.long 10.1093/jac/dkv412
spellingShingle QR Microbiology
RM Therapeutics. Pharmacology
RM300 Drugs and their action
RS Pharmacy and materia medica
Alobaid, Abdulaziz S.
Brinkmann, Alexander
Frey, Otto R.
Roehr, Anka C.
Luque, Sonia
Grau, Santiago
Wong , Gloria
Abdul Aziz, Mohd. Hafiz
Roberts, Michael S.
Lipman, Jeffrey
Roberts, Jason A.
What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?
title What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?
title_full What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?
title_fullStr What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?
title_full_unstemmed What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?
title_short What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?
title_sort what is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?
topic QR Microbiology
RM Therapeutics. Pharmacology
RM300 Drugs and their action
RS Pharmacy and materia medica
url http://irep.iium.edu.my/46717/
http://irep.iium.edu.my/46717/
http://irep.iium.edu.my/46717/
http://irep.iium.edu.my/46717/1/J._Antimicrob._Chemother.-2015-Alobaid-jac-dkv412.pdf