Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Mohd H. Abdul-Aziz; Jeffrey Lipman; Murat Akova; Matteo Bassetti; Jan J. De Waele; George Dimopoulos; Joel Dulhunty; Kirsi Maija Kaukonen; Despoina Koulenti; Claude Martin; Philippe Montravers; Jordi Rello; Andrew Rhodes; Therese Starr; Steven C. Wallis; Jason A. Roberts; Sanjoy Paul; Antonio Margarit Ribas; Luc D. De Crop; Herbert Spapen; Joost Wauters; Thierry Dugernier; Philippe Jorens; Ilse Dapper; Daniel D. De Backer; Fabio S. Taccone; Laura Ruano; Elsa Afonso; Francisco Alvarez-Lerma; Maria Pilar Gracia-Arnillas; Francisco Fernández; Neus Feijoo; Neus Bardolet; Assumpta Rovira; Pau Garro; Diana Colon; Carlos Castillo; Juan Fernado; Maria Jesus Lopez; Jose Luis Fernandez; Ana Maria Arribas; Jose Luis Teja; Elsa Ots; Juan Carlos Montejo; Mercedes Catalan; Isidro Prieto; Gloria Gonzalo; Beatriz Galvan; Miguel Angel Blasco; Estibaliz Meyer; Frutos Del Nogal; Loreto Vidaur; Rosa Sebastian; Pila Marco Garde; Maria del Mar Martin Velasco; Rafael Zaragoza Crespo; Mariano Esperatti; Antoni Torres; Olivier Baldesi; Herve Dupont; Yazine Mahjoub; Sigismond Lasocki; Jean Michel Constantin; Jean François Payen; Jacques Albanese; Yannick Malledant; Julien Pottecher; Jean Yves Lefrant; Samir Jaber; Olivier Joannes-Boyau; Christophe Orban; Marlies Ostermann; Catherine McKenzie; Willaim Berry; John Smith; Katie Lei; Francesca Rubulotta; Anthony Gordon; Stephen Brett; Martin Stotz; Maie Templeton; Claudia Ebm; Carl Moran; Ville Pettilä; Aglaia Xristodoulou; Vassiliki Theodorou; Georgios Kouliatsis; Eleni Sertaridou; Georgios Anthopoulos; George Choutas; Thanos Rantis; Stylianos Karatzas; Margarita Balla; Metaxia Papanikolaou; Pavlos Myrianthefs; Alexandra Gavala; Georgios Fildisis; Antonia Koutsoukou; Magdalini Kyriakopoulou; Kalomoira Petrochilou

doi:10.1093/jac/dkv288

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Mohd H. Abdul-Aziz, Jeffrey Lipman, Murat Akova, Matteo Bassetti, Jan J. De Waele, George Dimopoulos, Joel Dulhunty, Kirsi Maija Kaukonen, Despoina Koulenti, Claude Martin, Philippe Montravers, Jordi Rello, Andrew Rhodes, Therese Starr, Steven C. Wallis, Jason A. Roberts, Sanjoy Paul, Antonio Margarit Ribas, Luc D. De Crop, Herbert SpapenJoost Wauters, Thierry Dugernier, Philippe Jorens, Ilse Dapper, Daniel D. De Backer, Fabio S. Taccone, Laura Ruano, Elsa Afonso, Francisco Alvarez-Lerma, Maria Pilar Gracia-Arnillas, Francisco Fernández, Neus Feijoo, Neus Bardolet, Assumpta Rovira, Pau Garro, Diana Colon, Carlos Castillo, Juan Fernado, Maria Jesus Lopez, Jose Luis Fernandez, Ana Maria Arribas, Jose Luis Teja, Elsa Ots, Juan Carlos Montejo, Mercedes Catalan, Isidro Prieto, Gloria Gonzalo, Beatriz Galvan, Miguel Angel Blasco, Estibaliz Meyer, Frutos Del Nogal, Loreto Vidaur, Rosa Sebastian, Pila Marco Garde, Maria del Mar Martin Velasco, Rafael Zaragoza Crespo, Mariano Esperatti, Antoni Torres, Olivier Baldesi, Herve Dupont, Yazine Mahjoub, Sigismond Lasocki, Jean Michel Constantin, Jean François Payen, Jacques Albanese, Yannick Malledant, Julien Pottecher, Jean Yves Lefrant, Samir Jaber, Olivier Joannes-Boyau, Christophe Orban, Marlies Ostermann, Catherine McKenzie, Willaim Berry, John Smith, Katie Lei, Francesca Rubulotta, Anthony Gordon, Stephen Brett, Martin Stotz, Maie Templeton, Claudia Ebm, Carl Moran, Ville Pettilä, Aglaia Xristodoulou, Vassiliki Theodorou, Georgios Kouliatsis, Eleni Sertaridou, Georgios Anthopoulos, George Choutas, Thanos Rantis, Stylianos Karatzas, Margarita Balla, Metaxia Papanikolaou, Pavlos Myrianthefs, Alexandra Gavala, Georgios Fildisis, Antonia Koutsoukou, Magdalini Kyriakopoulou, Kalomoira Petrochilou

Department of Medicine

Research output: Contribution to journal › Article › Research › peer-review

96 Citations (Scopus)

Abstract

© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT≥MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of ≥ 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections.

Original language	English
Pages (from-to)	196-207
Journal	Journal of Antimicrobial Chemotherapy
Volume	71
Issue number	1
DOIs	https://doi.org/10.1093/jac/dkv288
Publication status	Published - 1 Jan 2016

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Abdul-Aziz, M. H., Lipman, J., Akova, M., Bassetti, M., De Waele, J. J., Dimopoulos, G., Dulhunty, J., Kaukonen, K. M., Koulenti, D., Martin, C., Montravers, P., Rello, J., Rhodes, A., Starr, T., Wallis, S. C., Roberts, J. A., Paul, S., Ribas, A. M., De Crop, L. D., ... Petrochilou, K. (2016). Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort. Journal of Antimicrobial Chemotherapy, 71(1), 196-207. https://doi.org/10.1093/jac/dkv288

Abdul-Aziz, Mohd H. ; Lipman, Jeffrey ; Akova, Murat ; Bassetti, Matteo ; De Waele, Jan J. ; Dimopoulos, George ; Dulhunty, Joel ; Kaukonen, Kirsi Maija ; Koulenti, Despoina ; Martin, Claude ; Montravers, Philippe ; Rello, Jordi ; Rhodes, Andrew ; Starr, Therese ; Wallis, Steven C. ; Roberts, Jason A. ; Paul, Sanjoy ; Ribas, Antonio Margarit ; De Crop, Luc D. ; Spapen, Herbert ; Wauters, Joost ; Dugernier, Thierry ; Jorens, Philippe ; Dapper, Ilse ; De Backer, Daniel D. ; Taccone, Fabio S. ; Ruano, Laura ; Afonso, Elsa ; Alvarez-Lerma, Francisco ; Gracia-Arnillas, Maria Pilar ; Fernández, Francisco ; Feijoo, Neus ; Bardolet, Neus ; Rovira, Assumpta ; Garro, Pau ; Colon, Diana ; Castillo, Carlos ; Fernado, Juan ; Lopez, Maria Jesus ; Fernandez, Jose Luis ; Arribas, Ana Maria ; Teja, Jose Luis ; Ots, Elsa ; Montejo, Juan Carlos ; Catalan, Mercedes ; Prieto, Isidro ; Gonzalo, Gloria ; Galvan, Beatriz ; Blasco, Miguel Angel ; Meyer, Estibaliz ; Nogal, Frutos Del ; Vidaur, Loreto ; Sebastian, Rosa ; Garde, Pila Marco ; Velasco, Maria del Mar Martin ; Crespo, Rafael Zaragoza ; Esperatti, Mariano ; Torres, Antoni ; Baldesi, Olivier ; Dupont, Herve ; Mahjoub, Yazine ; Lasocki, Sigismond ; Constantin, Jean Michel ; Payen, Jean François ; Albanese, Jacques ; Malledant, Yannick ; Pottecher, Julien ; Lefrant, Jean Yves ; Jaber, Samir ; Joannes-Boyau, Olivier ; Orban, Christophe ; Ostermann, Marlies ; McKenzie, Catherine ; Berry, Willaim ; Smith, John ; Lei, Katie ; Rubulotta, Francesca ; Gordon, Anthony ; Brett, Stephen ; Stotz, Martin ; Templeton, Maie ; Ebm, Claudia ; Moran, Carl ; Pettilä, Ville ; Xristodoulou, Aglaia ; Theodorou, Vassiliki ; Kouliatsis, Georgios ; Sertaridou, Eleni ; Anthopoulos, Georgios ; Choutas, George ; Rantis, Thanos ; Karatzas, Stylianos ; Balla, Margarita ; Papanikolaou, Metaxia ; Myrianthefs, Pavlos ; Gavala, Alexandra ; Fildisis, Georgios ; Koutsoukou, Antonia ; Kyriakopoulou, Magdalini ; Petrochilou, Kalomoira. / Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort. In: Journal of Antimicrobial Chemotherapy. 2016 ; Vol. 71, No. 1. pp. 196-207.

@article{fc5e49cbc4ed4cc9aac4c4111c0e64e0,

title = "Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort",

abstract = "{\textcopyright} The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT≥MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of ≥ 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections.",

author = "Abdul-Aziz, {Mohd H.} and Jeffrey Lipman and Murat Akova and Matteo Bassetti and {De Waele}, {Jan J.} and George Dimopoulos and Joel Dulhunty and Kaukonen, {Kirsi Maija} and Despoina Koulenti and Claude Martin and Philippe Montravers and Jordi Rello and Andrew Rhodes and Therese Starr and Wallis, {Steven C.} and Roberts, {Jason A.} and Sanjoy Paul and Ribas, {Antonio Margarit} and {De Crop}, {Luc D.} and Herbert Spapen and Joost Wauters and Thierry Dugernier and Philippe Jorens and Ilse Dapper and {De Backer}, {Daniel D.} and Taccone, {Fabio S.} and Laura Ruano and Elsa Afonso and Francisco Alvarez-Lerma and Gracia-Arnillas, {Maria Pilar} and Francisco Fern{\'a}ndez and Neus Feijoo and Neus Bardolet and Assumpta Rovira and Pau Garro and Diana Colon and Carlos Castillo and Juan Fernado and Lopez, {Maria Jesus} and Fernandez, {Jose Luis} and Arribas, {Ana Maria} and Teja, {Jose Luis} and Elsa Ots and Montejo, {Juan Carlos} and Mercedes Catalan and Isidro Prieto and Gloria Gonzalo and Beatriz Galvan and Blasco, {Miguel Angel} and Estibaliz Meyer and Nogal, {Frutos Del} and Loreto Vidaur and Rosa Sebastian and Garde, {Pila Marco} and Velasco, {Maria del Mar Martin} and Crespo, {Rafael Zaragoza} and Mariano Esperatti and Antoni Torres and Olivier Baldesi and Herve Dupont and Yazine Mahjoub and Sigismond Lasocki and Constantin, {Jean Michel} and Payen, {Jean Fran{\c c}ois} and Jacques Albanese and Yannick Malledant and Julien Pottecher and Lefrant, {Jean Yves} and Samir Jaber and Olivier Joannes-Boyau and Christophe Orban and Marlies Ostermann and Catherine McKenzie and Willaim Berry and John Smith and Katie Lei and Francesca Rubulotta and Anthony Gordon and Stephen Brett and Martin Stotz and Maie Templeton and Claudia Ebm and Carl Moran and Ville Pettil{\"a} and Aglaia Xristodoulou and Vassiliki Theodorou and Georgios Kouliatsis and Eleni Sertaridou and Georgios Anthopoulos and George Choutas and Thanos Rantis and Stylianos Karatzas and Margarita Balla and Metaxia Papanikolaou and Pavlos Myrianthefs and Alexandra Gavala and Georgios Fildisis and Antonia Koutsoukou and Magdalini Kyriakopoulou and Kalomoira Petrochilou",

year = "2016",

month = jan,

day = "1",

doi = "10.1093/jac/dkv288",

language = "English",

volume = "71",

pages = "196--207",

number = "1",

}

Abdul-Aziz, MH, Lipman, J, Akova, M, Bassetti, M, De Waele, JJ, Dimopoulos, G, Dulhunty, J, Kaukonen, KM, Koulenti, D, Martin, C, Montravers, P, Rello, J, Rhodes, A, Starr, T, Wallis, SC, Roberts, JA, Paul, S, Ribas, AM, De Crop, LD, Spapen, H, Wauters, J, Dugernier, T, Jorens, P, Dapper, I, De Backer, DD, Taccone, FS, Ruano, L, Afonso, E, Alvarez-Lerma, F, Gracia-Arnillas, MP, Fernández, F, Feijoo, N, Bardolet, N, Rovira, A, Garro, P, Colon, D, Castillo, C, Fernado, J, Lopez, MJ, Fernandez, JL, Arribas, AM, Teja, JL, Ots, E, Montejo, JC, Catalan, M, Prieto, I, Gonzalo, G, Galvan, B, Blasco, MA, Meyer, E, Nogal, FD, Vidaur, L, Sebastian, R, Garde, PM, Velasco, MDMM, Crespo, RZ, Esperatti, M, Torres, A, Baldesi, O, Dupont, H, Mahjoub, Y, Lasocki, S, Constantin, JM, Payen, JF, Albanese, J, Malledant, Y, Pottecher, J, Lefrant, JY, Jaber, S, Joannes-Boyau, O, Orban, C, Ostermann, M, McKenzie, C, Berry, W, Smith, J, Lei, K, Rubulotta, F, Gordon, A, Brett, S, Stotz, M, Templeton, M, Ebm, C, Moran, C, Pettilä, V, Xristodoulou, A, Theodorou, V, Kouliatsis, G, Sertaridou, E, Anthopoulos, G, Choutas, G, Rantis, T, Karatzas, S, Balla, M, Papanikolaou, M, Myrianthefs, P, Gavala, A, Fildisis, G, Koutsoukou, A, Kyriakopoulou, M & Petrochilou, K 2016, 'Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort', Journal of Antimicrobial Chemotherapy, vol. 71, no. 1, pp. 196-207. https://doi.org/10.1093/jac/dkv288

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort. / Abdul-Aziz, Mohd H.; Lipman, Jeffrey; Akova, Murat; Bassetti, Matteo; De Waele, Jan J.; Dimopoulos, George; Dulhunty, Joel; Kaukonen, Kirsi Maija; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C.; Roberts, Jason A.; Paul, Sanjoy; Ribas, Antonio Margarit; De Crop, Luc D.; Spapen, Herbert; Wauters, Joost; Dugernier, Thierry; Jorens, Philippe; Dapper, Ilse; De Backer, Daniel D.; Taccone, Fabio S.; Ruano, Laura; Afonso, Elsa; Alvarez-Lerma, Francisco; Gracia-Arnillas, Maria Pilar; Fernández, Francisco; Feijoo, Neus; Bardolet, Neus; Rovira, Assumpta; Garro, Pau; Colon, Diana; Castillo, Carlos; Fernado, Juan; Lopez, Maria Jesus; Fernandez, Jose Luis; Arribas, Ana Maria; Teja, Jose Luis; Ots, Elsa; Montejo, Juan Carlos; Catalan, Mercedes; Prieto, Isidro; Gonzalo, Gloria; Galvan, Beatriz; Blasco, Miguel Angel; Meyer, Estibaliz; Nogal, Frutos Del; Vidaur, Loreto; Sebastian, Rosa; Garde, Pila Marco; Velasco, Maria del Mar Martin; Crespo, Rafael Zaragoza; Esperatti, Mariano; Torres, Antoni; Baldesi, Olivier; Dupont, Herve; Mahjoub, Yazine; Lasocki, Sigismond; Constantin, Jean Michel; Payen, Jean François; Albanese, Jacques; Malledant, Yannick; Pottecher, Julien; Lefrant, Jean Yves; Jaber, Samir; Joannes-Boyau, Olivier; Orban, Christophe; Ostermann, Marlies; McKenzie, Catherine; Berry, Willaim; Smith, John; Lei, Katie; Rubulotta, Francesca; Gordon, Anthony; Brett, Stephen; Stotz, Martin; Templeton, Maie; Ebm, Claudia; Moran, Carl; Pettilä, Ville; Xristodoulou, Aglaia; Theodorou, Vassiliki; Kouliatsis, Georgios; Sertaridou, Eleni; Anthopoulos, Georgios; Choutas, George; Rantis, Thanos; Karatzas, Stylianos; Balla, Margarita; Papanikolaou, Metaxia; Myrianthefs, Pavlos; Gavala, Alexandra; Fildisis, Georgios; Koutsoukou, Antonia; Kyriakopoulou, Magdalini; Petrochilou, Kalomoira.

In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 1, 01.01.2016, p. 196-207.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

AU - Abdul-Aziz, Mohd H.

AU - Lipman, Jeffrey

AU - Akova, Murat

AU - Bassetti, Matteo

AU - De Waele, Jan J.

AU - Dimopoulos, George

AU - Dulhunty, Joel

AU - Kaukonen, Kirsi Maija

AU - Koulenti, Despoina

AU - Martin, Claude

AU - Montravers, Philippe

AU - Rello, Jordi

AU - Rhodes, Andrew

AU - Starr, Therese

AU - Wallis, Steven C.

AU - Roberts, Jason A.

AU - Paul, Sanjoy

AU - Ribas, Antonio Margarit

AU - De Crop, Luc D.

AU - Spapen, Herbert

AU - Wauters, Joost

AU - Dugernier, Thierry

AU - Jorens, Philippe

AU - Dapper, Ilse

AU - De Backer, Daniel D.

AU - Taccone, Fabio S.

AU - Ruano, Laura

AU - Afonso, Elsa

AU - Alvarez-Lerma, Francisco

AU - Gracia-Arnillas, Maria Pilar

AU - Fernández, Francisco

AU - Feijoo, Neus

AU - Bardolet, Neus

AU - Rovira, Assumpta

AU - Garro, Pau

AU - Colon, Diana

AU - Castillo, Carlos

AU - Fernado, Juan

AU - Lopez, Maria Jesus

AU - Fernandez, Jose Luis

AU - Arribas, Ana Maria

AU - Teja, Jose Luis

AU - Ots, Elsa

AU - Montejo, Juan Carlos

AU - Catalan, Mercedes

AU - Prieto, Isidro

AU - Gonzalo, Gloria

AU - Galvan, Beatriz

AU - Blasco, Miguel Angel

AU - Meyer, Estibaliz

AU - Nogal, Frutos Del

AU - Vidaur, Loreto

AU - Sebastian, Rosa

AU - Garde, Pila Marco

AU - Velasco, Maria del Mar Martin

AU - Crespo, Rafael Zaragoza

AU - Esperatti, Mariano

AU - Torres, Antoni

AU - Baldesi, Olivier

AU - Dupont, Herve

AU - Mahjoub, Yazine

AU - Lasocki, Sigismond

AU - Constantin, Jean Michel

AU - Payen, Jean François

AU - Albanese, Jacques

AU - Malledant, Yannick

AU - Pottecher, Julien

AU - Lefrant, Jean Yves

AU - Jaber, Samir

AU - Joannes-Boyau, Olivier

AU - Orban, Christophe

AU - Ostermann, Marlies

AU - McKenzie, Catherine

AU - Berry, Willaim

AU - Smith, John

AU - Lei, Katie

AU - Rubulotta, Francesca

AU - Gordon, Anthony

AU - Brett, Stephen

AU - Stotz, Martin

AU - Templeton, Maie

AU - Ebm, Claudia

AU - Moran, Carl

AU - Pettilä, Ville

AU - Xristodoulou, Aglaia

AU - Theodorou, Vassiliki

AU - Kouliatsis, Georgios

AU - Sertaridou, Eleni

AU - Anthopoulos, Georgios

AU - Choutas, George

AU - Rantis, Thanos

AU - Karatzas, Stylianos

AU - Balla, Margarita

AU - Papanikolaou, Metaxia

AU - Myrianthefs, Pavlos

AU - Gavala, Alexandra

AU - Fildisis, Georgios

AU - Koutsoukou, Antonia

AU - Kyriakopoulou, Magdalini

AU - Petrochilou, Kalomoira

PY - 2016/1/1

Y1 - 2016/1/1

N2 - © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT≥MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of ≥ 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections.

AB - © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT≥MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of ≥ 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections.

U2 - 10.1093/jac/dkv288

DO - 10.1093/jac/dkv288

M3 - Article

VL - 71

SP - 196

EP - 207

IS - 1

ER -

Abdul-Aziz MH, Lipman J, Akova M, Bassetti M, De Waele JJ, Dimopoulos G et al. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort. Journal of Antimicrobial Chemotherapy. 2016 Jan 1;71(1):196-207. https://doi.org/10.1093/jac/dkv288