Article
Infectious Diseases
Vesa Cheng, Mohd H. Abdul-Aziz, Fay Burrows, Hergen Buscher, Amanda Corley, Arne Diehl, Stephan M. Jakob, Bianca J. Levkovich, Vincent Pellegrino, Yok-Ai Que, Claire Reynolds, Sam Rudham, Steven C. Wallis, Susan A. Welch, David Zacharias, Jason A. Roberts, Kiran Shekar, John F. Fraser
Summary: This study aimed to describe the population pharmacokinetics of cefepime during ECMO and identify an optimal dosing strategy through dosing simulations. Reduced cefepime clearance was observed in ECMO patients, increasing the risk of cefepime toxicity. Modified dosing regimens should be used to avoid drug accumulation in critically ill patients on ECMO.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Review
Critical Care Medicine
Jason A. Roberts, Rinaldo Bellomo, Menino O. Cotta, Birgit C. P. Koch, Haifa Lyster, Marlies Ostermann, Claire Roger, Kiran Shekar, Kevin Watt, Mohd H. Abdul-Aziz
Summary: Intensive care unit patients with end-organ failure often require specialized machines or extracorporeal therapies, such as renal replacement therapy and extracorporeal membrane oxygenation, to support failing organs. However, these therapies can affect the metabolism and clearance of antimicrobial drugs, which may impact the effectiveness of antimicrobial therapy. Therefore, understanding these effects is crucial for achieving successful antimicrobial treatment in patients receiving these therapies.
INTENSIVE CARE MEDICINE
(2022)
Article
Microbiology
Jongsung Hahn, Kyoung Lok Min, Soyoung Kang, Seungwon Yang, Min Soo Park, Jin Wi, Min Jung Chang
Summary: This study aimed to investigate the impact of critical illness and extracorporeal circulation on the pharmacokinetics of piperacillin-tazobactam in critically ill patients, and develop a population pharmacokinetic model to determine the optimal dosage regimen for achieving the pharmacodynamic target. The findings suggest that continuous infusion should be considered in patients with creatinine clearance of $60 mL/min, irrespective of ECMO or CVVHDF, to achieve adequate target attainment. Further research on high continuous infusion doses focused on the risk of toxicity is warranted.
MICROBIOLOGY SPECTRUM
(2021)
Review
Medicine, General & Internal
Saikat Mitra, Ryan Ruiyang Ling, Chuen Seng Tan, Kiran Shekar, Graeme MacLaren, Kollengode Ramanathan
Summary: This systematic review and meta-analysis analyzed outcomes of patients receiving renal replacement therapy (RRT) on extracorporeal membrane oxygenation (ECMO) from January 2000 to September 2020. The study found that RRT on ECMO was associated with higher mortality rates and longer ICU/hospital stay compared to those without RRT. In the last five years, mortality decreased by 20% in patients receiving RRT, but there is still an increased risk of death. Future research should focus on minimizing renal dysfunction and determining the optimal timing for initiating RRT in ECMO patients.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Medicine, General & Internal
Dana Bakdach, Reem Elajez, Abdul Rahman Bakdach, Ahmed Awaisu, Gennaro De Pascale, Ali Ait Hssain
Summary: This review discusses and summarizes the available literature on the pharmacokinetic/pharmacodynamic (PK/PD) indices of novel beta-lactam antibiotics (NBLA) among critically ill patients with special circumstances. The evidence is limited by small sample sizes and high heterogeneity. Obesity and/or extracorporeal membrane oxygenation (ECMO) have minimal effects on the PK/PD target attainments of NBLA, while renal functionality (augmented renal clearance or renal replacement therapies) has a more substantial impact.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Sarah Kim, Nicholas L. Stucky, Wendi Drummond, Fawzy Elbarbry, Brent W. Footer
Summary: The presence of ECMO in critical ill patients can affect the pharmacokinetics and pharmacodynamics of drugs. This case report studied the serum concentrations of ampicillin in two patients on ECMO with E. faecalis infections. Pharmacokinetic parameters were calculated and the results showed that the ampicillin concentrations were above the MIC for the entire dosing interval. This report demonstrates that therapeutic concentrations of ampicillin can be achieved in ECMO patients with the use of therapeutic drug monitoring.
Article
Pharmacology & Pharmacy
Yixue Wang, Weiming Chen, Yidie Huang, Guangfei Wang, Zhiping Li, Gangfeng Yan, Chao Chen, Guoping Lu
Summary: The study aimed to establish a population pharmacokinetic model of meropenem in children with sepsis receiving ECLS and optimize dosage regimens based on PTA. Body weight and creatinine clearance were found to significantly impact PK parameters, while ECMO intervention showed no relation to PK properties. Recommendations for optimized dosing regimens were provided based on PTA results for children with different body weights, estimated creatinine clearances, and bacterial MIC levels.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Engineering, Biomedical
Carina E. Imburgia, Joseph E. Rower, Danielle J. Green, Autumn M. Mcknite, Walter E. Kelley, Christopher A. Reilly, Kevin M. Watt
Summary: The study found significant drug loss of RDV and its metabolite in ECMO and CRRT circuits, mainly due to drug adsorption by circuit materials or efficient hemodiafiltration.
Article
Engineering, Biomedical
Mohammed Hamzah, Troy G. Seelhammer, Mouhammad Yabrodi, Asaad G. Beshish, Jonathan W. Byrnes, James Hall, Lu Wang, Robert A. Niebler
Summary: Bivalirudin offers important advantages in managing ECMO patients, but the dose needs to be adjusted based on renal function. The initial dose depends on eGFR and further dose adjustments guided by laboratory monitoring are necessary.
Article
Anesthesiology
Marc Vives, Keyvan Karkouti, Vivek Rao, C. T. Chan, Duminda N. Wijeysundera
Summary: A comparison study was conducted on the outcomes and costs of transitioning from continuous RRT to SLED for severe CSA-AKI patients. The study found that using SLED resulted in reduced costs compared to continuous RRT, with no significant differences in outcomes such as LCOS, mortality, and other major outcomes in CSA-AKI patients.
JOURNAL OF CLINICAL ANESTHESIA
(2022)
Article
Engineering, Biomedical
Michael A. Lahart, Emily L. Burns, Madison M. Streb, Hongjie Gu, Tara M. Neumayr, Aaron M. Abarbanell, Ahmed S. Said
Summary: There is limited information on the dosing of bivalirudin in pediatric ECMO patients requiring CRRT. This study found no difference in bivalirudin dosing between pediatric ECMO patients who required CRRT and those who did not. Younger age and lower weight were associated with higher bivalirudin dosing.
Article
Microbiology
Matthias Gijsen, Erwin Dreesen, Pieter Annaert, Johan Nicolai, Yves Debaveye, Joost Wauters, Isabel Spriet
Summary: This study aimed to evaluate the effect of ECMO on the pharmacokinetic variability and target attainment of meropenem in critically ill patients. The results showed poor target attainment of meropenem under standard dosing, but ECMO was not found to influence this. Future studies should focus on dose optimization strategies based on renal function.
Article
Critical Care Medicine
Kathryn Chappell, Lauren A. Kimmons, J. Tyler Haller, Robert B. Canada, Hui He, Joanna Q. Hudson
Summary: The study found substantial clearance of levetiracetam with both CRRT and SLED modalities, highlighting the potential for subtherapeutic concentrations with current dosing strategies that only consider kidney function.
JOURNAL OF CRITICAL CARE
(2021)
Article
Pharmacology & Pharmacy
Qinghua Ye, Xin Yu, Wenqian Chen, Min Li, Sichao Gu, Linna Huang, Qingyuan Zhan, Chen Wang
Summary: This study assessed the impact of extracorporeal membrane oxygenation (ECMO) on voriconazole exposure and found that ECMO, in addition to drug interactions, is a significant factor affecting voriconazole exposure.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Holger Thiele, Uwe Zeymer, Ibrahim Akin, Michael Behnes, Tienush Rassaf, Amir Abbas Mahabadi, Ralf Lehmann, Ingo Eitel, Tobias Graf, Tim Seidler, Andreas Schuster, Carsten Skurk, Daniel Duerschmied, Peter Clemmensen, Marcus Hennersdorf, Stephan Fichtlscherer, Ingo Voigt, Melchior Seyfarth, Stefan John, Sebastian Ewen, Axel Linke, Eike Tigges, Peter Nordbeck, Leonhard Bruch, Christian Jung, Jutta Franz, Philipp Lauten, Tomaz Goslar, Hans-Josef Feistritzer, Janine Poess, Eva Kirchhof, Taoufik Ouarrak, Steffen Schneider, Steffen Desch, Anne Freund, ECLS-SHOCK Investigators
Summary: In patients with acute myocardial infarction complicated by cardiogenic shock, early extracorporeal life support (ECLS) combined with standard medical treatment did not reduce mortality.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Amy Legg, Niamh Meagher, Sandra A. Johnson, Matthew A. Roberts, Alan Cass, Marc H. Scheetz, Jane Davies, Jason A. Roberts, Joshua S. Davis, Steven Y. C. Tong
Summary: The clinical risk factors for nephrotoxicity in Staphylococcus aureus bacteraemia are still unclear. In a clinical trial comparing standard therapy to combination therapy, it was found that the combination therapy group had a significantly higher incidence of acute kidney injury.
CLINICAL DRUG INVESTIGATION
(2023)
Article
Medical Laboratory Technology
Lucy Sharrock, Melissa J. Ankravs, Adam M. Deane, Thomas Rechnitzer, Steven C. Wallis, Jason A. Roberts, Rinaldo Bellomo
Summary: This study measured the clearance of piperacillin-tazobactam and vancomycin in patients receiving CVVHDF with regional citrate anticoagulation, and found that both drugs have high clearance, providing key information for optimal dosing.
THERAPEUTIC DRUG MONITORING
(2023)
Letter
Infectious Diseases
Chandra Datta Sumi, Jason A. Roberts, Fekade B. Sime
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Ming G. Chai, Jason A. Roberts, Andras Farkas, Menino O. Cotta
Summary: This study demonstrates that precision dosing software programs can reasonably predict antibiotic concentrations in critically ill patients with sepsis. The addition of therapeutic drug monitoring (TDM) data improves the predictive performance of the software for all three antibiotics and the ability to anticipate the correct dose change required.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Review
Virology
Chuan Kok Lim, Jason Roberts, Michael Moso, Kwee Chin Liew, Mona L. Taouk, Eloise Williams, Thomas Tran, Eike Steinig, Leon Caly, Deborah Ann Williamson
Summary: This review discusses the changes in the epidemiology of monkeypox and the advancements in the understanding of its virology and viral dynamics relevant to diagnostics. It outlines the traditional and emerging laboratory technologies useful for monkeypox virus detection and in guiding elimination strategies. Importantly, the development in MPXV genomics has rapidly advanced our understanding of viral evolution and adaptation in the current outbreak.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Pharmacology & Pharmacy
Paul Williams, Menino Osbert Cotta, Mohd H. H. Abdul-Aziz, Kathryn Wilks, Andras Farkas, Jason A. A. Roberts
Summary: This study aimed to compare the achievement of therapeutic PK-PD exposure targets for beta-lactam antibiotics using product information dosing or guideline-based dosing for serious infections. In silico simulations were performed, and the results showed that guideline-based dosing had significantly higher probability of target attainment at 48 and 96 hours compared to product information dosing. The study also found that eGFR was significantly associated with the %PTA by guideline-based dosing.
Article
Urology & Nephrology
Carla E. Scuderi, Suzanne L. Parker, Margaret Jacks, George T. John, Brett McWhinney, Jacobus Ungerer, Andrew J. Mallett, Helen G. Healy, Jason A. Roberts, Christine E. Staatz
Summary: This study aimed to assess the diagnostic accuracy of using volumetric absorptive microsamplers (VAMS) to measure tacrolimus and creatinine in kidney transplant recipients. The results showed that VAMS can reliably measure tacrolimus and creatinine, providing a less invasive and more frequent sampling method for patients.
Article
Microbiology
Pier Giorgio Cojutti, Aaron J. Heffernan, Thomas Tangden, Paola Della Siega, Carlo Tascini, Jason A. Roberts, Federico Pea
Summary: This study aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of valganciclovir for preemptive therapy of cytomegalovirus (CMV) infection in kidney transplant patients. Ganciclovir concentrations and CMV viral loads were retrospectively obtained from kidney transplant patients. Monte Carlo simulations were conducted to assess the probability of attaining viral load targets, and a PK/PD model was devised.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biochemical Research Methods
Maria Patricia Hernandez-Mitre, Hayoung Won, Steven C. Wallis, Suzanne L. Parker, Jason A. Roberts
Summary: The aim of this study was to investigate the stability of nafamostat in infusion solutions, during blood sample collection, and in extracted plasma samples in the autosampler. Nafamostat was found to be stable in infusion solutions and in whole blood collected in sodium fluoride/potassium oxalate tubes at 4 degrees C for up to 3 hours before centrifugation. However, nafamostat degraded at a rate of 4.7 +/- 0.7% per hour in extracted plasma samples in the autosampler. In conclusion, viable samples can be obtained using appropriate collection tubes and prompt processing.
Review
Pharmacology & Pharmacy
Gavin Matthew Joynt, Lowell Ling, Wai Tat Wong, Jeffrey Lipman
Summary: The importance of antibiotic treatment for sepsis in critically ill septic patients is well known. However, achieving the correct dosage of antibiotics is a challenge. Understanding the pharmacokinetic and pharmacodynamic characteristics of antibiotics in critically ill patients is reshaping how they are dosed.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2023)
Review
Infectious Diseases
Eko Setiawan, Menino Osbert Cotta, Jason A. Roberts, Mohd Hafiz Abdul-Aziz
Summary: While inter-ethnic differences in the pharmacokinetic variabilities of antimicrobials have been studied among healthy subjects, further investigation is needed to understand the differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions. A systematic review was conducted to explore the potential variations in antimicrobial pharmacokinetics between Asian and non-Asian populations, with the inclusion of thirty studies on different antimicrobial agents. Inconsistent differences in pharmacokinetic parameters were observed between Asian and non-Asian patients, suggesting that ethnicity may not be a significant predictor in characterizing these differences, and dosing regimens should be adjusted based on demographic or clinical characteristics.
Article
Infectious Diseases
Francisco Beraldi-Magalhaes, Suzanne L. L. Parker, Cristina Sanches, Leandro Sousa Garcia, Brenda Karoline Souza Carvalho, Amanda Araujo Costa, Mariana Millan Fachi, Marcus Vinicius de Liz, Alexandra Brito de Souza, Izabella Picinin Safe, Roberto Pontarolo, Steven Wallis, Jeffrey Lipman, Jason A. A. Roberts, Marcelo Cordeiro-Santos
Summary: This study compared the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide, and ethambutol in tuberculosis patients in intensive care units (ICU) and outpatients, and evaluated drug serum concentrations as a potential cause of mortality. The results showed that ICU patients had a lower clearance and volume of distribution for these drugs, and the 30-day mortality rate was 77% compared to an 89% cure rate in outpatients. These differences may reflect changes in organ function, absorption, and distribution to the site of infection in ICU patients, which could impact clinical outcomes.
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2023)
Article
Infectious Diseases
Jason A. Roberts, David P. Nicolau, Ignacio Martin-Loeches, C. Andrew Deryke, Maria C. Losada, Jiejun Du, Munjal Patel, Matthew L. Rizk, Amanda Paschke, Luke F. Chen
Summary: The study aimed to assess the relationship between renal function and the efficacy/safety of imipenem/cilastatin/relebactam for the treatment of HABP/VABP. The results showed that the efficacy of imipenem/cilastatin/relebactam was comparable to piperacillin/tazobactam for participants with various baseline renal functions. However, for participants with normal renal function or CLCR >= 250ml/min, imipenem/cilastatin/relebactam had a higher clinical response rate.
JAC-ANTIMICROBIAL RESISTANCE
(2023)
Article
Anesthesiology
Sylvain Goutelle, Florent Wallet, Yann Thoma, Jean-Remix Peclard, Laurent Bourguignon, Sabine Cohen, Eric Kipnis, Jason Roberts, Bernard Allaouchiche, Arnaud Friggeri
ANAESTHESIA CRITICAL CARE & PAIN MEDICINE
(2023)