Article
Microbiology
D. Busse, P. Simon, D. Petroff, N. El-Najjar, L. Schmitt, D. Bindellini, A. Dietrich, M. Zeitlinger, W. Huisinga, R. Michelet, H. Wrigge, C. Kloft
Summary: The objectives of this study were to identify the appropriate body size descriptor for fosfomycin dose adjustments and assess the adequacy of the currently employed dosing regimens in both obese and nonobese patients. The study showed that dosing should be guided by renal function rather than obesity status.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Maxwell T. Chirehwa, Richard Court, Mariana de Kock, Lubbe Wiesner, Nihal de Vries, Joseph Harding, Tawanda Gumbo, Gary Maartens, Rob Warren, Paolo Denti, Helen McIlleron
Summary: This study investigated the use of ethionamide in treating multidrug-resistant and rifampicin-resistant tuberculosis, focusing on the distribution of MICs, pharmacokinetics, and probability of achieving target concentrations. Results showed that the WHO-recommended doses of ethionamide were inadequate in achieving target concentrations even for the lowest MIC measured in the cohort.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Roxane Rohani, Paul R. Yarnold, Marc H. Scheetz, Michael N. Neely, Mengjia Kang, Helen K. Donnelly, Kay Dedicatoria, Sophie H. Nozick, Rachel L. Medernach, Alan R. Hauser, Egon A. Ozer, Estefani Diaz, Alexander V. Misharin, Richard G. Wunderink, Nathaniel J. Rhodes
Summary: This study aimed to investigate the difference in target attainment of meropenem between plasma and epithelial lining fluid (ELF). The study found that some patients did not achieve the target attainment in both plasma and ELF, and those who achieved target attainment in plasma did not necessarily have the same effect in ELF. Patients with a higher creatinine clearance rate may have poorer target attainment in ELF. Additionally, the dosage and loading dose may also affect the target attainment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Immunology
Magnus Bock, Anna Marie Theut, Johan G. C. van Hasselt, Hengzhuang Wang, Kurt Fuursted, Niels Hoiby, Christian Johann Lerche, Nikolaj Ihlemann, Sabine Gill, Ulrik Christiansen, Hans Linde Nielsen, Lars Lemming, Hanne Elming, Jonas A. Povlsen, Niels Eske Bruun, Dan Hofsten, Emil L. Fosbol, Lars Kober, Martin Schultz, Mia M. Pries-Heje, Jonas Henrik Kristensen, Jens Jorgen Christensen, Flemming S. Rosenvinge, Christian Torp Pedersen, Jannik Helweg-Larsen, Niels Tonder, Kasper Iversen, Henning Bundgaard, Claus Moser
Summary: Pharmacokinetic/pharmacodynamic analyses were conducted to assess the probabilities of target attainment for oral treatments of infective endocarditis. The majority of patients achieved the target level with orally administered antibiotics, supporting the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Roxane Rohani, Marc H. Scheetz, Helen K. Donnelly, Alvaro Donayre, Mengjia Kang, Estefani Diaz, Kay Dedicatoria, Alan R. Hauser, Egon A. Ozer, Sophia Nozick, Chao Qi, Anna E. Pawlowski, Michael N. Neely, Alexander Misharin, Richard G. Wunderink, Nathaniel J. Rhodes
Summary: Critical illness affects the attainment of pharmacokinetic/pharmacodynamic (PK/PD) targets. This study aimed to quantify PK/PD attainment in patients with hospital-acquired pneumonia. The results showed that individualized treatment is required to achieve suggested PK/PD targets.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Anna K. Tietjen, Niklas Kroemer, Dario Cattaneo, Sara Baldelli, Sebastian G. Wicha
Summary: This study found that a dose of 300 mg twice daily of linezolid may not be sufficient to treat patients with multidrug-resistant tuberculosis from a pharmacokinetic/pharmacodynamic perspective. It is therefore recommended to start with a higher dose of 600 mg twice daily to ensure PK/PD target attainment. Therapeutic drug monitoring and MIC determination should be performed to control PK/PD target attainment due to high variability in linezolid's PK in the TB population.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Immunology
Kristina M. Bigelow, Amelia N. Deitchman, Si-Yang Li, Kala Barnes-Boyle, Sandeep Tyagi, Heena Soni, Kelly E. Dooley, Rada M. Savic, Eric L. Nuermberger
Summary: This study investigated the pharmacokinetic/pharmacodynamic relationships of linezolid in the treatment of tuberculosis, showing that time above minimum inhibitory concentration (T->MIC) was most correlated with efficacy, but area under the concentration-time curve over MIC (AUC/MIC) was equally predictive in growth-constrained conditions. Additionally, red blood cell counts were strongly correlated with LW minimum concentration (C-min).
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Romain Guilhaumou, Constance Chevrier, Jean Loup Setti, Elisabeth Jouve, Amelie Marsot, Nathan Julian, Olivier Blin, Pierre Simeone, David Lagier, Djamel Mokart, Nicolas Bruder, Marc Garnier, Lionel Velly
Summary: This study aimed to describe the pharmacokinetic/pharmacodynamic target attainment of continuously infused beta-lactam antibiotics in ICU patients and evaluate the impact of dosage adjustment. The results showed that the empirical dosages of beta-lactam antibiotics were often lower than recommended. Indexed creatinine clearance was associated with dosage underdosing or overdosing. Adjusting the dosage improved target attainment. This study provides important insights into optimizing beta-lactam therapy for ICU patients.
Article
Microbiology
Muhammad Bilal, Michael Zoller, Uwe Fuhr, Ulrich Jaehde, Sami Ullah, Uwe Liebchen, Soeren Buesker, Johannes Zander, Baharak Babouee Flury, Max Taubert
Summary: Cefepime has concentration-related neurotoxicity, especially in critically ill patients with renal failure. Through population pharmacokinetic modeling and Monte Carlo simulations, a dosing regimen for Cefepime was identified with the highest probability of target attainment and the lowest risk of neurotoxicity in critically ill patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Iris K. Minichmayr, Sebastian G. Wicha, Peter Matzneller, Charlotte Kloft, Markus Zeitlinger
Summary: This study aims to evaluate the impact of the key components of the intensified dosing regimen on the pharmacokinetic/pharmacodynamic target attainment considering different levels of bacterial susceptibility.
CLINICAL PHARMACOKINETICS
(2023)
Article
Chemistry, Medicinal
Saki Takahashi, Yasuhiro Tsuji, Hidefumi Kasai, Chika Ogami, Hitoshi Kawasuji, Yoshihiro Yamamoto, Hideto To
Summary: Linezolid-induced thrombocytopenia is associated with linezolid exposure, baseline platelet count, and patient background. Machine learning-based CART analysis identified predictive factors and cutoff values for predicting thrombocytopenia. Monitoring linezolid concentration and platelet count change from baseline at an early stage may help prevent thrombocytopenia induced by linezolid.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Microbiology
Joshua A. Reeder, Cormac T. O'Sullivan, Min Xu, Nan Wu, Dilek Ince, William K. Rogers, Guohua An
Summary: The study aimed to investigate the population pharmacokinetics of ampicillin-sulbactam in surgical patients undergoing prolonged surgery with antibiotic redosing. A population pharmacokinetic model was developed, revealing that creatinine clearance and heart failure affected clearance, while body surface area influenced the central volume of distribution. Monte Carlo simulations showed that the recommended 2-hour redosing scheme was overly conservative, and a 4-hour redosing interval with a 3-g dose could achieve the desired target in all populations. The study suggests revising the current redosing guidelines and customizing prophylaxis recommendations based on local susceptibility patterns.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Sonya Tang Girdwood, Min Dong, Peter Tang, Erin Stoneman, Rhonda Jones, Toni Yunger, Austin Ostermeier, Calise Curry, Melissa Forton, Traci Hail, Randi Mullaney, Patrick Lahni, Nieko Punt, Jennifer Kaplan, Alexander A. Vinks
Summary: This study developed population PK models of ceftriaxone in children admitted to a pediatric intensive care unit (PICU) and evaluated different dosing regimens. The study found that patient weight, age, creatinine clearance, and temperature significantly affected ceftriaxone clearance, while the presence of sepsis and phase of illness did not have a significant effect on PK parameters.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Claudia Garcia Messiano, Ronaldo Morales Junior, Gabriela Otofuji Pereira, Elson Mendes da Silva Junior, David de Souza Gomez, Silvia Regina Cavani Jorge Santos
Summary: The purpose of this prospective cohort study was to evaluate the therapeutic target achievement of 3-hour extended infusion of meropenem in patients with septic burns in the early and late periods of septic shock. The study found that the therapeutic target was achieved when treating infections caused by gram-negative bacteria, such as Pseudomonas aeruginosa.
CLINICAL THERAPEUTICS
(2022)
Article
Infectious Diseases
Annabel Werumeus Buning, Caspar J. Hodiamont, Natalia M. Lechner, Margriet Schokkin, Paul W. G. Elbers, Nicole P. Juffermans, Ron A. A. Mathot, Menno D. de Jong, Reinier M. van Hest
Summary: This study aimed to describe the population pharmacokinetics of ceftazidime in critically ill patients with Pseudomonas aeruginosa infection, and found that patient characteristics and treatment methods can affect drug clearance, suggesting the use of loading doses for patients with proven or suspected P. aeruginosa infection.
Article
Pharmacology & Pharmacy
Zoe Oesterreicher, Sabine Eberl, Beatrix Wulkersdorfer, Peter Matzneller, Claudia Eder, Esther van Duijn, Wouter H. J. Vaes, Birgit Reiter, Thomas Stimpfl, Walter Jager, Alina Nussbaumer-Proell, Daniela Marhofer, Peter Marhofer, Oliver Langer, Markus Zeitlinger
Summary: This study confirms the feasibility of microdosing for pharmacokinetic measurements in plasma and subcutaneous tissue, and suggests that microdosing combined with microdialysis is a potentially useful tool in clinical antimicrobial drug development. Further studies are needed to assess its applicability for pulmonary pharmacokinetics with bronchoalveolar lavage.
CLINICAL PHARMACOKINETICS
(2022)
Article
Pharmacology & Pharmacy
Anselm Jorda, Jolanta M. Siller-Matula, Markus Zeitlinger, Bernd Jilma, Georg Gelbenegger
Summary: In patients with COVID-19, higher-dose anticoagulation compared to prophylactic-dose anticoagulation reduces the risk of thromboembolic events but increases the risk of major bleeding, with no significant impact on the risk of death.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Hans-Georg Eichler, Mark Trusheim, Brigitte Schwarzer-Daum, Kay Larholt, Markus Zeitlinger, Martin Brunninger, Michael Sherman, David Strutton, Gigi Hirsch
Summary: Basic scientists and drug developers are working on innovations towards precision medicine, but there are challenges in reimbursement and coverage for precision medicines. Stakeholders are exploring new payment models to address these challenges.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Infectious Diseases
Heimo Lagler, Christine Bangert, Tamara Quint, Zoe Osterreicher, Alina Nussbaumer-Proll, Sabine Eberl, Maria Weber, Matthias Karer, Morten O. A. Sommer, Markus Zeitlinger
Summary: This study compared three commonly used methods for sampling Staphylococcus aureus on atopic dermatitis skin lesions and investigated the effectiveness of skin disinfection. The results showed significant differences in quantifying S. aureus load between different sampling methods, highlighting the importance of method selection. Skin disinfection led to a reduction in S. aureus load, but complete eradication was not achieved. This data suggests the need for further clinical studies on the effectiveness of topical anti-staphylococcal antibiotics and consideration of alternative disinfection regimes in atopic dermatitis patients.
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Thomas P. Lodise, Matteo Bassetti, Ricard Ferrer, Thierry Naas, Yoshihito Niki, David L. Paterson, Markus Zeitlinger, Roger Echols
Summary: Pathogen-focused, randomized, controlled trials (PF-RCT) are crucial in the fight against carbapenem-resistant Gram-negative infections. Recent studies have investigated both new and older generic antibiotics in a variety of infections. However, PF-RCTs pose challenges due to heterogeneity in infection types, pathogens, and study design. Interpretation of data is further complicated by the lack of statistical analysis plans and limited power. While new antibiotics showed potential in reducing all-cause mortality in CR Enterobacterales infections, combinations of older generic antibiotics did not demonstrate the same effect in CR Acinetobacter spp. infections. More high-quality PF-RCTs are needed to evaluate the clinical benefit of drug-resistant infections.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2022)
Article
Microbiology
Mohammad H. Alshaer, Brooke Barlow, Nicole Maranchick, Miriam Moser, Leon Gramss, Heinz Burgmann, Valentin Al Jalali, Michael Woelfl-Duchek, Walter Jaeger, Stefan Poschner, Walter Ploechl, Andrea Reinprecht, Karl Roessler, Andreas Gruber, Markus Zeitlinger, Charles A. Peloquin, Arthur Hosmann
Summary: This study investigated the pharmacokinetics of Meropenem in the central nervous system and simulated dosing regimens. Continuous infusion was found to be more effective in achieving therapeutic targets compared to intermittent infusion, based on drug concentration measurements and brain tissue samples.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Felix Bergmann, Peter Matzneller, Maria Weber, Lusine Yeghiazaryan, Thorsten Fuereder, Thomas Weber, Markus Zeitlinger
Summary: Improving medical care, contributing to scientific research, and trusting treating physicians are the main motives for clinical trial participation among participants. Older patients have higher expectations of receiving optimal treatment during participation. Healthy volunteers with financial motives have participated in more clinical trials. Participants have high trust in medical staff and government research institutions, but low trust in pharmaceutical and health insurance companies.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Christoph Dorn, David Petroff, Alexander Kratzer, Frieder Kees, Charlotte Kloft, Markus Zeitlinger, Hermann Wrigge, Philipp Simon
Summary: This study investigated the concentrations of Tigecycline in plasma and subcutaneous tissue in obese patients compared to non-obese patients. The results showed that the concentrations of Tigecycline were lower in obese patients, indicating a need for an increased dose.
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
(2022)
Article
Infectious Diseases
K. Iqbal, H. Rohde, J. Huang, T. Tikiso, L. F. Amann, M. Zeitlinger, S. G. Wicha
Summary: This study assessed the pharmacokinetic-pharmacodynamic (PKPD) relationship for tedizolid against Enterococcus in the hollow-fibre infection model. The results indicated that the recommended human dose was insufficient to suppress bacterial growth.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Robin Michelet, Davide Bindellini, Johanna Melin, Uta Neumann, Oliver Blankenstein, Wilhelm Huisinga, Trevor N. Johnson, Martin J. Whitaker, Richard Ross, Charlotte Kloft
Summary: This study investigates the incorporation of maturation functions derived from the physiologically-based pharmacokinetic (PBPK) model into a non-linear mixed-effects (NLME) model to enhance the description of inter-individual variability in hydrocortisone pharmacokinetics (PK) for pediatric adrenal insufficiency patients and improve individualized dosing predictions.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Sabine Stuebler, Charlotte Kloft, Wilhelm Huisinga
Summary: A systems biology model of the intestinal immune system was developed to understand IBD and its treatment modalities. The model characterized patients based on phenotype rather than assumptions, allowing for replication of IBD predispositions. Analysis of different treatment effects provided insights into individual drug therapy characteristics.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Undine Falkenhagen, Jane Knoechel, Charlotte Kloft, Wilhelm Huisinga
Summary: Quantitative systems pharmacology (QSP) models integrate comprehensive qualitative and quantitative knowledge about pharmacologically relevant processes. We extend the approach of leveraging knowledge in QSP models to derive simpler pharmacodynamic models. The extended approach includes reduction of state, reaction rates, elimination of reactions, and maintenance of approximation quality for a diverse virtual population. The proposed model-reduction algorithm provides a systematic method to build pharmacodynamic models from QSP models in various applications.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Francis Williams Ojara, Andrea Henrich, Nicolas Frances, Yomna M. Nassar, Wilhelm Huisinga, Niklas Hartung, Kimberly Geiger, Stefan Holdenrieder, Markus Joerger, Charlotte Kloft
Summary: Joint analysis of demographic/clinical characteristics, blood biomarker levels, and chemotherapy exposure-driven early tumor response can improve the prediction of overall survival in patients with advanced non-small cell lung cancer (NSCLC). C-reactive protein (CRP) along with RS8, the tumor size reduction induced by paclitaxel exposure, significantly affects overall survival and can be used for individual prognostic predictions for different paclitaxel dosing regimens.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Franziska Kluwe, Robin Michelet, Wilhelm Huisinga, Markus Zeitlinger, Gerd Mikus, Charlotte Kloft
Summary: This study aimed to evaluate and compare the predictive performance of nonlinear mixed-effects (NLME) models for model-informed precision dosing (MIPD) of voriconazole, a broad-spectrum antifungal drug. The results showed that a published 'hybrid' model had the best predictive performance, but all NLME models had only modest predictive performance, indicating the need for further improvement in model development and evaluation.
CLINICAL PHARMACOKINETICS
(2023)
Article
Oncology
Yomna M. Nassar, Francis Williams Ojara, Alejandro Perez-Pitarch, Kimberly Geiger, Wilhelm Huisinga, Niklas Hartung, Robin Michelet, Stefan Holdenrieder, Markus Joerger, Charlotte Kloft
Summary: In oncology, C-reactive protein (CRP) concentrations have been found to be associated with the prognosis of lung cancer patients, particularly at the beginning of treatment cycle 3. Monitoring CRP concentrations as an indicator of inflammation and predictor of prognosis can help identify patients at risk and guide treatment decisions.