Article
Infectious Diseases
Marcus Tindall, Michael J. Chappell, James W. T. Yates
Summary: Mathematical modelling has played a significant role in optimizing the use of antimicrobial treatments. This article discusses the key processes that should be captured by such modelling, with a particular emphasis on quantifying the response of the host immune system and presenting a novel model structure.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
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
Computer Science, Interdisciplinary Applications
Iordanis Kesisoglou, Brianna M. Eales, Paul R. Merlau, Vincent H. Tam, Michael Nikolaou
Summary: The study presents a method for predicting the bactericidal efficacy of antibiotics using mathematical modeling and longitudinal optical density measurements. Experimental results confirm the effectiveness of periodic injections of ceftazidime/amikacin combinations in suppressing bacterial populations, while periodic injections of ceftazidime alone showed limited efficacy.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2022)
Article
Infectious Diseases
Zhe Tang, Jing Guan, Jingjing Li, Yanxia Yu, Miao Qian, Jing Cao, Weiwei Shuai, Zheng Jiao
Summary: Population pharmacokinetic/pharmacodynamic modeling was used to study the exposure target of vancomycin in neonates, resulting in dosing recommendations based on observed data. The study found that vancomycin exposure in neonates is influenced by factors such as physiological maturation, renal function, and concomitant use of vasoactive agents, with different exposure levels associated with clinical outcomes.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Review
Infectious Diseases
Gregory J. Peitz, Daryl J. Murry
Summary: Extracorporeal membrane oxygenation (ECMO) is a method used to support critically ill patients, but it poses challenges in terms of complications and medication optimization. A non-systematic review evaluated the pharmacokinetic parameters of commonly used anti-infectives in ECMO patients and found that they are similar to those in non-ECMO critically ill populations, but there is considerable variability between patients, indicating the need for further evaluation of therapeutic drug monitoring in this complex population.
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.
Review
Infectious Diseases
Erlangga Yusuf, Markus Zeitlinger, Sylvain Meylan
Summary: The interpretation of antimicrobial susceptibility testing results (S or R) is clear, but the "intermediate (I)" category poses difficulties. This review critically examines how clinical breakpoints are determined using pharmacokinetics and pharmacodynamics. It discusses the discrepancies in the "I" category between CLSI and EUCAST, and the recent changes in EUCAST definition and their impact on laboratory and clinical practices.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Laura Sibley, Andrew D. White, Charlotte Sarfas, Jennie Gullick, Fergus Gleeson, Faye Lanni, Simon Clark, Emma Rayner, Santiago Ferrer-Bazaga, Fatima Ortega-Muro, Laura Alameda, Joaquin Rullas, Veronica Sousa, Marisa Martinez, Inigo Angulo-Barturen, Adolfo Garcia, Juan Jose Vaquero, Henry E. Pertinez, Geraint Davies, Mike Dennis, Ann Williams, Sally Sharpe
Summary: Innovative cross-over study designs were explored in non-human primate studies to evaluate the effectiveness of drug treatments for tuberculosis. The pharmacokinetics of standard tuberculosis drugs were established in macaques, and two studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of different drug combinations using cross-over designs. The studies supported the utility of the non-human primate model for determining the pharmacokinetics and pharmacodynamics of tuberculosis drugs, but further optimization of cross-over study designs is needed.
Article
Immunology
Andrew D. McCallum, Henry E. Pertinez, Aaron P. Chirambo, Irene Sheha, Madalitso Chasweka, Rose Malamba, Doris Shani, Alex Chitani, Jane E. Mallewa, Jamilah Z. Meghji, Jehan F. Ghany, Elizabeth L. Corbett, Stephen B. Gordon, Geraint R. Davies, Saye H. Khoo, Derek J. Sloan, Henry C. Mwandumba
Summary: This study explores the relationship between intrapulmonary drug levels and sputum bacillary clearance in tuberculosis treatment. The results show that higher drug exposure to rifampicin or isoniazid in the epithelial lining fluid is associated with more rapid bacillary elimination. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration, and better treatment outcomes.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Kim Dao, Aline Fuchs, Pascal Andre, Eric Giannoni, Laurent A. Decosterd, Oscar Marchetti, Sandra A. Asner, Marc Pfister, Nicolas Widmer, Thierry Buclin, Chantal Csajka, Monia Guidi
Summary: This study aims to characterize the pharmacokinetics of Imipenem in neonates and evaluate the performance of different dosing regimens through simulations. The results demonstrate that dosing adjustment according to body weight, gestational age, and postnatal age optimizes Imipenem exposure in neonates.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Review
Infectious Diseases
Cornelia B. Landersdorfer, Amanda Gwee, Roger L. Nation
Summary: Traditionally, ongoing i.v. antibiotic therapy has been believed to be superior to early i.v. to oral switch for severe infections. However, this belief may not be based on robust data and contemporary clinical studies. This review examines the rationale for an early switch and discusses barriers and perceptions related to this practice.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Article
Pharmacology & Pharmacy
Luqman Vali, David R. Jenkins, Rakesh Vaja, Hussain Mulla
Summary: The study demonstrated that bedside Bayesian-guided personalised dosing of vancomycin in vascular surgery patients can increase the proportion of patients achieving target AUC(24) values and the percentage time in the target range.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Infectious Diseases
Jing Zhou, Li Jiang, Zhi-Ling Zhang, Zhao-Rui Wang, Yan-Xiu Zhang, Xu Lin, Bo-Hao Tang, Bu-Fan Yao, Zi-Xuan Guo, Jing-Jing Yang, John Van den Anker, Yue-E Wu, Wei Zhao
Summary: This study aims to describe the pharmacokinetic characteristics of mezlocillin in neonates and young infants, and propose the optimal dosing regimen based on the population pharmacokinetic model of mezlocillin. The results showed that a two-compartment model with first-order elimination can be used to describe the population pharmacokinetics of mezlocillin, and postmenstrual age, current weight, and serum creatinine concentration are the most important covariates.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Amedeo De Nicolo, Giacomo Stroffolini, Miriam Antonucci, Jacopo Mula, Elisa Delia De Vivo, Jessica Cusato, Alice Palermiti, Giuseppe Cariti, Giovanni Di Perri, Silvia Corcione, Francesco Giuseppe De Rosa, Antonio D'Avolio
Summary: This study investigated the long-term plasma pharmacokinetics of dalbavancin in outpatients with ABSSSI or osteoarticular infections who were treated with either one or two doses of 1500 mg. The results showed that dalbavancin exposure exceeded previously suggested pharmacodynamic targets, indicating a need for optimization in the treatment of osteoarticular infections.
Article
Infectious Diseases
Malika Chassan, Anne Hemonic, Didier Concordet
Summary: In piglet farming, the variability in drug exposure through drinking water is mainly influenced by water consumption behavior, drug concentration in water, and inter-individual variability in pharmacokinetic parameters. Water consumption behavior is the most important factor leading to significant exposure variations, followed by drug concentration in water and individual variability in PK parameters.
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)
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)
Article
Microbiology
Silvia Lopez-Argueello, Maria Montaner, Alaa R. M. Sayed, Antonio Oliver, Jurgen B. Bulitta, Bartolome Moya
Summary: Beta-lactam antibiotics have been effective against susceptible Pseudomonas aeruginosa, but their penetration ability and binding to penicillin-binding proteins (PBPs) in intact bacteria have not been well studied. This research investigated the time course of PBP binding and target site penetration of 15 compounds in P. aeruginosa PAO1. The results showed that PBPs 1-4 were considerably bound in lysed bacteria, but the binding was attenuated in intact bacteria for slow penetrating beta-lactams. Imipenem showed the highest killing effect, while other drugs had lower killing rates. The study also found a correlation between PBP5/6 binding and the rate of net influx and PBP access.
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.
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
Microbiology
Jessica R. R. Tait, Marina Harper, Sara Cortes-Lara, Kate E. E. Rogers, Carla Lopez-Causape, Thomas R. R. Smallman, Yinzhi Lang, Wee Leng Lee, Jieqiang Zhou, Jurgen B. Bulitta, Roger L. L. Nation, John D. D. Boyce, Antonio Oliver, Cornelia B. B. Landersdorfer
Summary: The study evaluated the efficacy of ceftolozane-tazobactam against multidrug-resistant hypermutable P. aeruginosa isolates in cystic fibrosis (CF) using the hollow-fiber infection model. Results showed that isolates CW41 and CW44 harbored preexisting resistant subpopulations while CW35 did not. This emphasizes the importance of using ceftolozane-tazobactam in combination with another antibiotic in CF patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Infectious Diseases
Souha S. Kanj, Sara F. Haddad, Jacques F. Meis, Paul E. Verweij, Andreas Voss, Riina Rautemaa-Richardson, Gabriel Levy-Hara, Anuradha Chowdhary, Abdul Ghafur, Roger Bruggemann, Abhijit M. Bal, Jeroen Schouten
Summary: The detrimental effect of secondary pathogens, including invasive fungal infections, in COVID-19 patients is highlighted. The diagnosis of pulmonary fungal infections becomes more challenging during the pandemic, especially regarding radiological findings and mycology test results interpretation. Prolonged hospitalization in ICU, coupled with underlying host factors, increases vulnerability to fungal infections. The heavy workload, redeployment of untrained staff, and inconsistent supply of protective equipment make strict adherence to infection control measures difficult for healthcare workers.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
Didi Bury, Tom F. W. Wolfs, Rob ter Heine, Eline W. Muilwijk, Kim C. M. van der Elst, Wim J. E. Tissing, Roger J. M. Brueggemann
Summary: This study investigated the pharmacokinetics of isavuconazole in a pediatric cohort and found low bioavailability after nasogastric tube administration. The drug exposures were within the expected range following intravenous administration, and the pharmacokinetics of total and unbound isavuconazole were reported with a 5-fold range in the unbound fraction.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Julia W. Korzilius, Michelle Gompelman, Guus T. J. Wezendonk, Nynke G. L. Jager, Chantal P. Rovers, Roger J. M. Brueggemann, Geert J. A. Wanten
Summary: This study aimed to determine the bioavailability of orally administered antimicrobial agents commonly used for treatment in SBS patients. The results showed that the bioavailability of selected antimicrobial agents in certain SBS patients appeared to be better than expected, providing a feasible treatment option. However, therapeutic drug monitoring should be part of the treatment process to safeguard adequate exposure in all patients, due to the large observed differences between patients.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Yaru Peng, Iris K. Minichmayr, Han Liu, Feifan Xie, Lena E. Friberg
Summary: This study used pharmacometric multistate modeling to investigate predictors of in-hospital mortality in critically ill patients treated with meropenem. The study found that creatinine clearance and the duration of unbound concentrations exceeding the minimum inhibitory concentration significantly influenced the transitions and survival outcome of the patients.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Eman I. K. Ibrahim, Mats O. Karlsson, Lena E. Friberg
Summary: This study developed a semi-mechanistic pharmacokinetic-pharmacodynamic modeling framework to investigate the relationship between systemic exposure to ibrutinib and its efficacy and toxicity biomarkers. The simulations showed that lower dosing schedules can reduce the incidence of hypertension without compromising the reduction in tumor burden compared to the approved dosing schedule.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Anders Thorsted, Anh Duc Pham, Lena E. Friberg, Elisabet I. Nielsen
Summary: Neutrophil granulocytes play a crucial role in the host's immune response against pathogens, and severe neutropenia can make individuals more vulnerable to infections. This study developed a mathematical model to characterize the kinetics of neutrophil-mediated bacterial killing and investigated the contribution of the immune system to the clearance of bacterial infections. The model successfully predicted data from both in vitro and in vivo studies and can be used to assess the capacity of the host immune response at an individual level.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(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)