Review
Infectious Diseases
Catarina Mendes Silva, Joao Pedro Baptista, Iolanda Santos, Paulo Martins
Summary: This systematic review searched for recommendations on antibiotic dosage adjustment for critically ill patients with augmented renal clearance (ARC). The findings suggest that increasing dosage and/or adjusting infusion modality are frequently needed to achieve the desired pharmacokinetic/pharmacodynamic (PK/PD) targets.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Review
Microbiology
Pedro Povoa, Patricia Moniz, Joao Goncalves Pereira, Luis Coelho
Summary: Choosing and managing antimicrobial dosing in critically ill patients is a significant challenge. The unstable pharmacokinetic status and rapidly changing clinical condition of these patients require consideration of multiple factors to maximize treatment effectiveness.
Article
Infectious Diseases
E. Salvador, M. Oualha, E. Bille, A. Beranger, F. Moulin, S. Benaboud, S. Boujaafar, I Gana, S. Urien, Y. Zheng, J. Toubiana, C. Briand, O. Bustarret, G. Geslain, S. Renolleau, J-M Treluyer, D. Hirt
Summary: The study aimed to establish a population PK model for cefazolin in critically ill children for optimal dosing regimens. Results indicated that continuous infusion of cefazolin was the best scheme to achieve the PK target of 100% fT (>4 x MIC), especially for children with normal or augmented renal function.
CLINICAL MICROBIOLOGY AND INFECTION
(2021)
Article
Pharmacology & Pharmacy
Noel Zahr, Saik Urien, Benoit Llopis, Gaelle Noe, Nadine Tissot, Kevin Bihan, Helga Junot, Clemence Marin, Bochra Mansour, Charles-Edouard Luyt, Alexandre Bleibtreu, Christian Funck-Brentano
Summary: This retrospective study investigated the pharmacokinetics of cefiderocol in adult patients and found that albumin binding and renal function were significant predictors of cefiderocol concentrations. The results suggest that individual adjustment of cefiderocol based on unbound drug concentration can optimize therapeutic efficacy.
Article
Nutrition & Dietetics
Roland N. Dickerson, Christin N. Crawford, Melissa K. Tsiu, Cara E. Bujanowski, Edward T. Van Matre, Joseph M. Swanson, Dina M. Filiberto, Gayle Minard
Summary: This study aimed to determine the prevalence of augmented renal clearance (ARC) in trauma patients receiving nutrition therapy. Results showed that 50% of patients exhibited ARC, with factors such as male gender, traumatic brain injury, higher injury severity score, younger age, lower serum creatinine concentration, and protein intake being associated with ARC. Patients with multiple risk factors for ARC should be closely monitored for renal dosing of electrolytes, nutrients, and medications.
Review
Pharmacology & Pharmacy
Denise H. Rhoney, Samuel A. Metzger, Nicholas R. Neslon
Summary: This scoping review summarized the evidence on Augmented Renal Clearance (ARC) in pediatric patients, revealing a variable prevalence of ARC in this population likely due to the lack of a standard definition and age-related factors not being consistently considered in studies. ARC was shown to impact the pharmacokinetics of antibiotics commonly used in pediatric patients, potentially requiring adjustments to standard dosing regimens.
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.
Article
Medicine, Research & Experimental
Brian W. Johnston, David Perry, Martyn Habgood, Miland Joshi, Anton Krige
Summary: This study aimed to describe the prevalence and associated risk factors for Augmented Renal Clearance (ARC) development in a large, single-center cohort in the United Kingdom. Age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and sepsis diagnosis were significantly associated with ARC development.
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
(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
Infectious Diseases
David P. Nicolau, Jan De Waele, Joseph L. Kuti, Luzelena Caro, Kajal B. Larson, Brian Yu, Elaine Gadzicki, Zhen Zeng, Elizabeth G. Rhee, Matthew L. Rizk
Summary: This study aimed to determine the adequacy of established ceftolozane/tazobactam dosing for patients with augmented renal clearance (ARC) and bacterial infection. The results showed that a 3 g C/T dose met pharmacodynamic targets for ceftolozane and tazobactam in patients with ARC, with mild to moderate treatment-emergent adverse events observed.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Infectious Diseases
Tim M. J. Ewoldt, Soma Bahmany, Alan Abdulla, Anouk E. Muller, Henrik Endeman, Birgit C. P. Koch
Summary: Standard antibiotic dosing is not suitable for critically ill patients due to altered pharmacokinetics. Knowledge of protein binding is important for optimizing antibiotic exposure. This study found significant differences in unbound fractions between trough and peak samples, not explained by concentration differences. Existing models have good sensitivity for high concentrations but low specificity for subtherapeutic concentrations.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Critical Care Medicine
Idoia Bilbao-Meseguer, Helena Barrasa, Alicia Rodriguez-Gascon, Eduardo Asin-Prieto, Javier Maynar, Jose Angel Sanchez-Izquierdo, Maria Angeles Solinis, Arantxazu Isla
Summary: Levetiracetam dosage regimens need to be re-evaluated in critically ill patients with augmented renal clearance. This study proposes new dosage recommendations, including extended infusions, continuous infusions, or higher doses than recommended, based on pharmacokinetic aspects and feasibility criteria. Further clinical studies are needed to confirm these results.
JOURNAL OF INTENSIVE CARE
(2022)
Article
Pharmacology & Pharmacy
Stan J. F. Hartman, Parth J. Upadhyay, Nienke N. Hagedoorn, Ron A. A. Mathot, Henriette A. Moll, Michiel van der Flier, Michiel F. Schreuder, Roger J. Bruggemann, Catherijne A. Knibbe, Saskia N. de Wildt
Summary: Ceftriaxone pharmacokinetics in critically ill children were determined using population pharmacokinetic modeling. Dosing guidelines were proposed for adequate target attainment.
CLINICAL PHARMACOKINETICS
(2021)
Article
Infectious Diseases
Sonia Luque, Adela Benitez-Cano, Leire Larranaga, Luisa Sorli, Maria Eugenia Navarrete, Nuria Campillo, Jesus Carazo, Isabel Ramos, Ramon Adalia, Santiago Grau
Summary: In critically ill patients treated with meropenem by extended or continuous infusion, there were no significant differences in drug exposure levels between patients with low body weight and normal body weight. The only factor independently associated with supratherapeutic drug exposure was a baseline estimated glomerular filtration rate (eGFR) < 90 mL/min.
Article
Nutrition & Dietetics
Guilhem Dreydemy, Alexis Coussy, Alexandre Lannou, Laurent Petit, Matthieu Biais, Cedric Carrie
Summary: This pilot study aimed to investigate the association between augmented renal clearance (ARC), urinary nitrogen loss, and muscle wasting in critically ill trauma patients. The findings suggest that patients with ARC have lower nitrogen balance and increased muscle loss in the first 10 days after ICU admission. The benefits of increased protein intake (>1.5 g/kg/day) in these patients are still a matter of controversy and require further randomized trials for confirmation.
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)
Editorial Material
Critical Care Medicine
Jan J. J. De Waele, Isabel Leroux-Roels, Pieter Depuydt
INTENSIVE CARE MEDICINE
(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.
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
Computer Science, Information Systems
Jarne Verhaeghe, Thomas De Corte, Christopher M. Sauer, Tom Hendriks, Olivier W. M. Thijssens, Femke Ongenae, Paul Elbers, Jan De Waele, Sofie Van Hoecke
Summary: This study developed risk models for atrial fibrillation (AF) in intensive care unit (ICU) patients using uncertainty quantification. The models showed good performance and accurate prediction of AF risk in multiple ICU datasets.
INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS
(2023)
Review
Infectious Diseases
Allison M. Hitchcock, Wesley D. Kufel, Keri A. Mastro Dwyer, Eric F. Sidman
Summary: Lenacapavir is a novel HIV-1 treatment option for patients with multidrug-resistant (MDR) HIV-1 infection. It has a favorable pharmacokinetic profile and has shown good tolerability and efficacy in clinical trials.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
Article
Infectious Diseases
Roberta Gagliardini, Alessandro Tavelli, Stefano Rusconi, Sergio Lo Caputo, Vincenzo Spagnuolo, Maria Mercedes Santoro, Andrea Costantini, Alessandra Vergori, Franco Maggiolo, Andrea Giacomelli, Giulia Burastero, Giordano Madeddu, Eugenia Quiros Roldan, Antonella d'Arminio Monforte, Andrea Antinori, Alessandro Cozzi-Lepri
Summary: This study evaluated multiple treatment failures to modern antiretroviral therapy in HIV-infected individuals and found that approximately 4% of them were difficult to treat. The difficult to treat group, compared to the non-difficult to treat group, was characterized by older age, higher prevalence of AIDS, lower CD4+ cell count, and higher risk of treatment failure.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
