The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

Jason A. Roberts; Gavin M. Joynt; Anna Lee; Gordon Choi; Rinaldo Bellomo; Salmaan Kanji; M. Yugan Mudaliar; Sandra L. Peake; DIanne Stephens; Fabio Silvio Taccone; Marta Ulldemolins; Miia Maaria Valkonen; Julius Agbeve; João P. Baptista; Vasileios Bekos; Clement Boidin; Alexander Brinkmann; Luke Buizen; Pedro Castro; C. Louise Cole; Jacques Creteur; Jan J. De Waele; Renae Deans; Glenn M. Eastwood; Leslie Escobar; Charles Gomersall; Rebecca Gresham; Janattul Ain Jamal; Stefan Kluge; Christina König; Vasilios P. Koulouras; Melissa Lassig-Smith; Pierre Francois Laterre; Katie Lei; Patricia Leung; Jean Yves Lefrant; Mireia Llauradó-Serra; Ignacio Martin-Loeches; Mohd Basri Mat Nor; Marlies Ostermann; Suzanne L. Parker; Jordi Rello; Darren M. Roberts; Michael S. Roberts; Brent Richards; Alejandro Rodríguez; Anka C. Roehr; Claire Roger; Leonardo Seoane; Mahipal Sinnollareddy; Eduardo Sousa; Dolors Soy; Anna Spring; Therese Starr; Jane Thomas; John Turnidge; Steven C. Wallis; Tricia Williams; Xavier Wittebole; Xanthi T. Zikou; Sanjoy K. Paul; Jeffrey Lipman; Max Andresen; Sónia F. Baltazar; Saber Barbar; Eulália Costa; Dominique Durand; Ricardo Freitas; Otto R. Frey; Yarmarly Guerra Valero; Margaret Haughton; Andreas Koeberer; Marin Kollef; Kerenaftali Klein; Ravindra Mehta; Cathy McKenzie; Laurent Muller; Priya Nair; Vineet Nayyar; Jenny L. Ordóñez Mejia; Georgia Laura Panagou; Jody Paxton; Leah Peck; Mayukh Samanta; Jean Louise Vincent; Ruth Wan; Helen Young

doi:10.1093/cid/ciaa224

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

Jason A. Roberts, Gavin M. Joynt, Anna Lee, Gordon Choi, Rinaldo Bellomo, Salmaan Kanji, M. Yugan Mudaliar, Sandra L. Peake, DIanne Stephens, Fabio Silvio Taccone, Marta Ulldemolins, Miia Maaria Valkonen, Julius Agbeve, João P. Baptista, Vasileios Bekos, Clement Boidin, Alexander Brinkmann, Luke Buizen, Pedro Castro, C. Louise ColeJacques Creteur, Jan J. De Waele, Renae Deans, Glenn M. Eastwood, Leslie Escobar, Charles Gomersall, Rebecca Gresham, Janattul Ain Jamal, Stefan Kluge, Christina König, Vasilios P. Koulouras, Melissa Lassig-Smith, Pierre Francois Laterre, Katie Lei, Patricia Leung, Jean Yves Lefrant, Mireia Llauradó-Serra, Ignacio Martin-Loeches, Mohd Basri Mat Nor, Marlies Ostermann, Suzanne L. Parker, Jordi Rello, Darren M. Roberts, Michael S. Roberts, Brent Richards, Alejandro Rodríguez, Anka C. Roehr, Claire Roger, Leonardo Seoane, Mahipal Sinnollareddy, Eduardo Sousa, Dolors Soy, Anna Spring, Therese Starr, Jane Thomas, John Turnidge, Steven C. Wallis, Tricia Williams, Xavier Wittebole, Xanthi T. Zikou, Sanjoy K. Paul, Jeffrey Lipman, Max Andresen, Sónia F. Baltazar, Saber Barbar, Eulália Costa, Dominique Durand, Ricardo Freitas, Otto R. Frey, Yarmarly Guerra Valero, Margaret Haughton, Andreas Koeberer, Marin Kollef, Kerenaftali Klein, Ravindra Mehta, Cathy McKenzie, Laurent Muller, Priya Nair, Vineet Nayyar, Jenny L. Ordóñez Mejia, Georgia Laura Panagou, Jody Paxton, Leah Peck, Mayukh Samanta, Jean Louise Vincent, Ruth Wan, Helen Young

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

93 Scopus citations

Abstract

Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P <. 05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

Original language	English
Pages (from-to)	1369-1378
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	72
Issue number	8
DOIs	https://doi.org/10.1093/cid/ciaa224
State	Published - Apr 15 2021

Keywords

beta-lactam
continuous renal replacement therapy
extended daily dialysis
pharmacokinetic
renal clearance

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Roberts, J. A., Joynt, G. M., Lee, A., Choi, G., Bellomo, R., Kanji, S., Mudaliar, M. Y., Peake, S. L., Stephens, DI., Taccone, F. S., Ulldemolins, M., Valkonen, M. M., Agbeve, J., Baptista, J. P., Bekos, V., Boidin, C., Brinkmann, A., Buizen, L., Castro, P., ... Young, H. (2021). The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study. Clinical Infectious Diseases, 72(8), 1369-1378. https://doi.org/10.1093/cid/ciaa224

@article{131d6bcb5dd64ec2a0e0fce29bd63bb0,

title = "The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study",

abstract = "Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P <. 05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.",

keywords = "beta-lactam, continuous renal replacement therapy, extended daily dialysis, pharmacokinetic, renal clearance",

author = "Roberts, {Jason A.} and Joynt, {Gavin M.} and Anna Lee and Gordon Choi and Rinaldo Bellomo and Salmaan Kanji and Mudaliar, {M. Yugan} and Peake, {Sandra L.} and DIanne Stephens and Taccone, {Fabio Silvio} and Marta Ulldemolins and Valkonen, {Miia Maaria} and Julius Agbeve and Baptista, {Jo{\~a}o P.} and Vasileios Bekos and Clement Boidin and Alexander Brinkmann and Luke Buizen and Pedro Castro and Cole, {C. Louise} and Jacques Creteur and {De Waele}, {Jan J.} and Renae Deans and Eastwood, {Glenn M.} and Leslie Escobar and Charles Gomersall and Rebecca Gresham and Jamal, {Janattul Ain} and Stefan Kluge and Christina K{\"o}nig and Koulouras, {Vasilios P.} and Melissa Lassig-Smith and Laterre, {Pierre Francois} and Katie Lei and Patricia Leung and Lefrant, {Jean Yves} and Mireia Llaurad{\'o}-Serra and Ignacio Martin-Loeches and {Mat Nor}, {Mohd Basri} and Marlies Ostermann and Parker, {Suzanne L.} and Jordi Rello and Roberts, {Darren M.} and Roberts, {Michael S.} and Brent Richards and Alejandro Rodr{\'i}guez and Roehr, {Anka C.} and Claire Roger and Leonardo Seoane and Mahipal Sinnollareddy and Eduardo Sousa and Dolors Soy and Anna Spring and Therese Starr and Jane Thomas and John Turnidge and Wallis, {Steven C.} and Tricia Williams and Xavier Wittebole and Zikou, {Xanthi T.} and Paul, {Sanjoy K.} and Jeffrey Lipman and Max Andresen and Baltazar, {S{\'o}nia F.} and Saber Barbar and Eul{\'a}lia Costa and Dominique Durand and Ricardo Freitas and Frey, {Otto R.} and {Guerra Valero}, Yarmarly and Margaret Haughton and Andreas Koeberer and Marin Kollef and Kerenaftali Klein and Ravindra Mehta and Cathy McKenzie and Laurent Muller and Priya Nair and Vineet Nayyar and {Ord{\'o}{\~n}ez Mejia}, {Jenny L.} and Panagou, {Georgia Laura} and Jody Paxton and Leah Peck and Mayukh Samanta and Vincent, {Jean Louise} and Ruth Wan and Helen Young",

note = "Publisher Copyright: {\textcopyright} 2020",

year = "2021",

month = apr,

day = "15",

doi = "10.1093/cid/ciaa224",

language = "English",

volume = "72",

pages = "1369--1378",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

number = "8",

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Roberts, JA, Joynt, GM, Lee, A, Choi, G, Bellomo, R, Kanji, S, Mudaliar, MY, Peake, SL, Stephens, DI, Taccone, FS, Ulldemolins, M, Valkonen, MM, Agbeve, J, Baptista, JP, Bekos, V, Boidin, C, Brinkmann, A, Buizen, L, Castro, P, Cole, CL, Creteur, J, De Waele, JJ, Deans, R, Eastwood, GM, Escobar, L, Gomersall, C, Gresham, R, Jamal, JA, Kluge, S, König, C, Koulouras, VP, Lassig-Smith, M, Laterre, PF, Lei, K, Leung, P, Lefrant, JY, Llauradó-Serra, M, Martin-Loeches, I, Mat Nor, MB, Ostermann, M, Parker, SL, Rello, J, Roberts, DM, Roberts, MS, Richards, B, Rodríguez, A, Roehr, AC, Roger, C, Seoane, L, Sinnollareddy, M, Sousa, E, Soy, D, Spring, A, Starr, T, Thomas, J, Turnidge, J, Wallis, SC, Williams, T, Wittebole, X, Zikou, XT, Paul, SK, Lipman, J, Andresen, M, Baltazar, SF, Barbar, S, Costa, E, Durand, D, Freitas, R, Frey, OR, Guerra Valero, Y, Haughton, M, Koeberer, A, Kollef, M, Klein, K, Mehta, R, McKenzie, C, Muller, L, Nair, P, Nayyar, V, Ordóñez Mejia, JL, Panagou, GL, Paxton, J, Peck, L, Samanta, M, Vincent, JL, Wan, R & Young, H 2021, 'The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study', Clinical Infectious Diseases, vol. 72, no. 8, pp. 1369-1378. https://doi.org/10.1093/cid/ciaa224

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study. / Roberts, Jason A.; Joynt, Gavin M.; Lee, Anna et al.
In: Clinical Infectious Diseases, Vol. 72, No. 8, 15.04.2021, p. 1369-1378.

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

TY - JOUR

T1 - The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients

T2 - Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

AU - Roberts, Jason A.

AU - Joynt, Gavin M.

AU - Lee, Anna

AU - Choi, Gordon

AU - Bellomo, Rinaldo

AU - Kanji, Salmaan

AU - Mudaliar, M. Yugan

AU - Peake, Sandra L.

AU - Stephens, DIanne

AU - Taccone, Fabio Silvio

AU - Ulldemolins, Marta

AU - Valkonen, Miia Maaria

AU - Agbeve, Julius

AU - Baptista, João P.

AU - Bekos, Vasileios

AU - Boidin, Clement

AU - Brinkmann, Alexander

AU - Buizen, Luke

AU - Castro, Pedro

AU - Cole, C. Louise

AU - Creteur, Jacques

AU - De Waele, Jan J.

AU - Deans, Renae

AU - Eastwood, Glenn M.

AU - Escobar, Leslie

AU - Gomersall, Charles

AU - Gresham, Rebecca

AU - Jamal, Janattul Ain

AU - Kluge, Stefan

AU - König, Christina

AU - Koulouras, Vasilios P.

AU - Lassig-Smith, Melissa

AU - Laterre, Pierre Francois

AU - Lei, Katie

AU - Leung, Patricia

AU - Lefrant, Jean Yves

AU - Llauradó-Serra, Mireia

AU - Martin-Loeches, Ignacio

AU - Mat Nor, Mohd Basri

AU - Ostermann, Marlies

AU - Parker, Suzanne L.

AU - Rello, Jordi

AU - Roberts, Darren M.

AU - Roberts, Michael S.

AU - Richards, Brent

AU - Rodríguez, Alejandro

AU - Roehr, Anka C.

AU - Roger, Claire

AU - Seoane, Leonardo

AU - Sinnollareddy, Mahipal

AU - Sousa, Eduardo

AU - Soy, Dolors

AU - Spring, Anna

AU - Starr, Therese

AU - Thomas, Jane

AU - Turnidge, John

AU - Wallis, Steven C.

AU - Williams, Tricia

AU - Wittebole, Xavier

AU - Zikou, Xanthi T.

AU - Paul, Sanjoy K.

AU - Lipman, Jeffrey

AU - Andresen, Max

AU - Baltazar, Sónia F.

AU - Barbar, Saber

AU - Costa, Eulália

AU - Durand, Dominique

AU - Freitas, Ricardo

AU - Frey, Otto R.

AU - Guerra Valero, Yarmarly

AU - Haughton, Margaret

AU - Koeberer, Andreas

AU - Kollef, Marin

AU - Klein, Kerenaftali

AU - Mehta, Ravindra

AU - McKenzie, Cathy

AU - Muller, Laurent

AU - Nair, Priya

AU - Nayyar, Vineet

AU - Ordóñez Mejia, Jenny L.

AU - Panagou, Georgia Laura

AU - Paxton, Jody

AU - Peck, Leah

AU - Samanta, Mayukh

AU - Vincent, Jean Louise

AU - Wan, Ruth

AU - Young, Helen

PY - 2021/4/15

Y1 - 2021/4/15

N2 - Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P <. 05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

AB - Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P <. 05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

KW - beta-lactam

KW - continuous renal replacement therapy

KW - extended daily dialysis

KW - pharmacokinetic

KW - renal clearance

UR - http://www.scopus.com/inward/record.url?scp=85105765911&partnerID=8YFLogxK

U2 - 10.1093/cid/ciaa224

DO - 10.1093/cid/ciaa224

M3 - Article

C2 - 32150603

AN - SCOPUS:85105765911

SN - 1058-4838

VL - 72

SP - 1369

EP - 1378

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 8

ER -

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

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