Article
Infectious Diseases
Julie Gorham, Fabio S. Taccone, Maya Hites
Summary: Obesity is associated with increased risks of comorbidities, postoperative infections, and nosocomial infections. The pharmacokinetics and pharmacodynamics of antibiotics are affected by obesity, leading to increased risks of antibiotic therapy failure and toxicity. Precision dosing of antibiotics using therapeutic drug monitoring may improve the management of critically ill obese patients with infections.
Review
Critical Care Medicine
Nozomi Takahashi, Yutaka Kondo, Kenji Kubo, Moritoki Egi, Ken-ichi Kano, Yoshiyasu Ohshima, Taka-aki Nakada
Summary: This study conducted a systematic review and meta-analysis to evaluate the effectiveness of TDM-based regimen in critically ill patients. The results showed that TDM-based regimens had no significant efficacy for clinical or pharmacological outcomes. Further studies with other achievable targets and well-defined outcomes are required.
JOURNAL OF INTENSIVE CARE
(2023)
Review
Pharmacology & Pharmacy
Andrew J. Fratoni, David P. Nicolau, Joseph L. Kuti
Summary: Therapeutic drug monitoring (TDM) is important for personalized medicine, but rarely used for beta-lactam antibiotics. Increasing understanding of beta-lactam pharmacodynamics and pharmacokinetics variability has highlighted the potential of TDM. However, challenges in operation and result interpretation, as well as limited availability of necessary instrumentation and expertise, hinder widespread adoption.
Article
Pharmacology & Pharmacy
Sergey Zyryanov, Irina Bondareva, Olga Butranova, Alexandra Kazanova
Summary: This study aimed to determine the population pharmacokinetic parameters of meropenem in preterm infants and evaluate the pharmacodynamic indices and covariates affecting pharmacokinetics. Analysis of demographic, clinical, and therapeutic drug monitoring data from 66 preterm newborns revealed that the median values for elimination rate and volume of distribution of meropenem were 0.31 1/h and 1.2 L respectively, and the median values for total clearance and elimination half-life were 0.22 L/h/kg and 2.33 h. Individualized Bayesian posterior models improved prediction quality compared to the population model.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Infectious Diseases
Amy Legg, Sinead Carmichael, Ming G. Chai, Jason A. Roberts, Menino O. Cotta
Summary: Beta-lactam antibiotics are commonly used in critically ill patients to treat infections, but the optimal exposure targets for these drugs are still debated. Overcoming pharmacokinetic and pharmacodynamic challenges in the intensive care unit is necessary to achieve desired exposures. Therapeutic drug monitoring has shown promise for determining if the desired exposures are reached, but more research is needed to determine its impact on infection-related outcomes. Improving the efficiency of sampling and reporting results in at-risk patients is important for an ideal beta-lactam TDM service.
Review
Immunology
Rekha Pai Mangalore, Aadith Ashok, Sue J. Lee, Lorena Romero, Trisha N. Peel, Andrew A. Udy, Anton Y. Peleg
Summary: TDM-guided dosing of beta-lactam antibiotics improved clinical and microbiological cure in critically ill patients, with no significant impact on mortality and length of stay.
CLINICAL INFECTIOUS DISEASES
(2022)
Review
Immunology
Rekha Pai Mangalore, Aadith Ashok, Sue J. Lee, Lorena Romero, Trisha N. Peel, Andrew A. Udy, Anton Y. Peleg
Summary: This article conducted a systematic review and meta-analysis on the relationship between TDM-guided dosing and clinical outcomes in critically ill patients. The results showed that TDM-guided dosing improved clinical cure, microbiological cure, and treatment response. However, the impact on mortality and length of stay remains unclear and further research is needed.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Maria Aquino, Maria Tinoco, Joana Bicker, Amilcar Falcao, Marilia Rocha, Ana Fortuna
Summary: Amikacin is the preferred antibiotic for treating Gram-negative infections in neutropenic oncology patients. However, there is a lack of population pharmacokinetic studies on amikacin in this patient population. This large-scale retrospective study investigated the effects of tumor diseases, chemotherapy, lag time, age, and renal function on amikacin pharmacokinetics in neutropenic cancer patients. The results showed that oncology patients received higher daily doses of amikacin and had increased drug clearance. Chemotherapy influenced amikacin pharmacokinetics and drug clearance decreased with longer lag time. The impact of aging on amikacin doses was stronger than chemotherapy. This research suggests that cancer patients may require higher initial doses of amikacin, especially within 30 days of starting chemotherapy.
Review
Infectious Diseases
Jan Stasek, Filip Keller, Veronika Koci, Jozef Klucka, Eva Klabusayova, Ondrej Wiewiorka, Zuzana Strasilova, Miroslava Benovska, Marketa Skardova, Jan Malaska
Summary: Beta-lactam antibiotics are widely used in critical care due to their safety and efficacy. Achieving adequate plasma concentrations of antibiotics is crucial for effective treatment, but this can be challenging in critically ill patients due to physiological changes. Therapeutic drug monitoring (TDM) has proven to be effective in ensuring appropriate antibiotic concentrations, but there are limitations, such as long turnaround times. Further research is needed to determine if TDM can improve patient outcomes.
Article
Infectious Diseases
Pierre Chauvelot, Celine Dupieux-Chabert, Lelia Abad, Aubin Souche, Tristan Ferry, Jerome Josse, Frederic Laurent, Florent Valour
Summary: The study demonstrated that dalbavancin has the ability to effectively eradicate intraosteoblastic reservoir of Staphylococcus aureus in bone and joint infections. It showed significant reduction in bacterial inoculum at both low concentration and standard therapeutic doses, with similar efficacy to vancomycin but less efficient than rifampicin. Dalbavancin was found to be the only molecule significantly active at a low concentration.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Mengmeng Jia, Qiwen Zhang, Zifei Qin, Dao Wang, Peng Liu, Jing Yang, Xiaojian Zhang
Summary: This study aimed to investigate an appropriate dosing regimen and assess the exposure-response relationships of posaconazole (PCZ) in children. The study found that the dosage of PCZ varied depending on the age and purpose of treatment in children. Lower PCZ concentrations were associated with unsuccessful prophylaxis, while higher PCZ concentrations were associated with positive clinical response in treatment. Factors such as age, inflammatory markers, liver function indicators, and co-administration with proton pump inhibitors significantly affected PCZ concentrations.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Microbiology
Bruce R. Dalton
Summary: Therapeutic drug monitoring for vancomycin has shifted its focus from trough concentrations to area under the curve (AUC(24)). However, the evidence for this change is weak, with retrospective analyses and animal studies lacking conviction. In vitro data also present conflicting results. Therefore, the adoption of AUC(24):MIC based on animal experiments and in vitro evidence may be premature for vancomycin.
Review
Biochemistry & Molecular Biology
Julie Gorham, Fabio Silvio Taccone, Maya Hites
Summary: This review emphasizes the importance of appropriate antibiotic dosing in critically ill patients and provides an overview of the basic principles of pharmacokinetics, different approaches to adjust doses, and relevant information on therapeutic drug monitoring. The study found that dose adjustment for aminoglycosides and glycopeptides should be based on daily drug concentration monitoring. For glycopeptides, particularly vancomycin, the residual concentration (Cres) should be assessed daily. Loading dose should be administered for beta-lactam antibiotics, followed by three different possible approaches for dose adjustment.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Anne-Grete Martson, Gena Burch, Samiksha Ghimire, Jan-Willem C. Alffenaar, Charles A. Peloquin
Summary: Therapeutic drug monitoring (TDM) is recommended for tuberculosis (TB) treatment optimization but is currently only used in a few countries. This review provides an update on drugs used in TB, treatment strategies, and TDM. Individualizing treatment using TDM may help reduce adverse effects and poor treatment outcomes. Funding, training, and randomized controlled trials are necessary to advance TDM for TB patients.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Eduard Schmulenson, Nigina Zimmermann, Gerd Mikus, Markus Joerger, Ulrich Jaehde
Summary: New data on 5FU-TDM strengthen its advantages over BSA-guided dosing, as it can reduce pharmacokinetic variability to improve treatment efficacy and safety. Interprofessional collaboration can help overcome barriers for implementation. Pharmacogenetic testing followed by 5FU-TDM can enhance 5FU exposure for many patients, with a model framework integrating pharmacokinetics and pharmacodynamics being crucial for precision medicine advancement.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
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)
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
Pharmacology & Pharmacy
Eko Setiawan, Menino Osbert Cotta, Mohd-Hafiz Abdul-Aziz, Doddy Widjanarko, Hernycane Sosilya, Dwi Lily Lukas, Steven C. Wallis, Suzanne Parker, Jason A. Roberts
Summary: This study investigated the pharmacokinetics of ampicillin-sulbactam in patients with a wide range of renal functions and found that serum creatinine was closely associated with drug clearance. Furthermore, a 4-hour infusion was found to enhance the probability of target attainment and fractional target attainment, especially at higher minimum inhibitory concentrations.
CLINICAL PHARMACOKINETICS
(2023)
Article
Chemistry, Analytical
Shuping Qiang, Fahim Mohamed, Lorraine Mackenzie, Michael S. Roberts
Summary: The potential exposure to glyphosate-based herbicides, including suicide attempts, is a global concern. The toxicokinetics of polyethoxylated tallow amine (POEA) surfactants after exposure is limited, due to the lack of suitable analysis methods. A robust LC-MSMS method was developed and validated for the rapid analysis of 11 POEA homologues in human plasma. The analysis of POEA surfactants plasma concentrations is crucial for assessing internal exposure and the relationships between glyphosate toxicity and poisoning extent.
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
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.
Review
Infectious Diseases
Amy Legg, Sinead Carmichael, Ming G. Chai, Jason A. Roberts, Menino O. Cotta
Summary: Beta-lactam antibiotics are commonly used in critically ill patients to treat infections, but the optimal exposure targets for these drugs are still debated. Overcoming pharmacokinetic and pharmacodynamic challenges in the intensive care unit is necessary to achieve desired exposures. Therapeutic drug monitoring has shown promise for determining if the desired exposures are reached, but more research is needed to determine its impact on infection-related outcomes. Improving the efficiency of sampling and reporting results in at-risk patients is important for an ideal beta-lactam TDM service.
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
Biochemistry & Molecular Biology
Krishna C. Telaprolu, Jeffrey E. Grice, Yousuf H. Mohammed, Michael S. Roberts
Summary: The distribution of esterase enzymes in different layers of human skin and their contributions to drug metabolism are poorly understood. In this study, methyl salicylate cream was tested on various human skin membranes to investigate esterase distribution. The results showed similar permeation of methyl salicylate across all membranes, suggesting dermal esterase activity. Staining studies also confirmed that esterase activity was mainly present in the dermal-epidermal junction region of the dermis rather than the epidermis.