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
Infectious Diseases
Jessica R. Tait, Hajira Bilal, Tae Hwan Kim, Abigail Oh, Anton Y. Peleg, John D. Boyce, Antonio Oliver, Phillip J. Bergen, Roger L. Nation, Cornelia B. Landersdorfer
Summary: The study showed that the combination of ceftazidime and tobramycin has a good bactericidal effect and can suppress resistance in hypermutable Pseudomonas aeruginosa strains. In vitro experiments simulating treatment regimens revealed that high-dose combination therapy is more effective against susceptible strains.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2021)
Review
Pharmacology & Pharmacy
Alicia Rodriguez-Gascon, Maria angeles Solinis, Arantxa Isla
Summary: PK/PD analysis is essential in establishing rational dosage regimens of antimicrobial agents in human and veterinary medicine. It involves the use of different models and mathematical models to determine optimal dosing regimens and prevent the emergence of resistance. PK/PD analysis plays a crucial role in the development of new antibiotics and optimization of current drug dosage regimens.
Review
Pharmacology & Pharmacy
Li Zhou, Micaela B. Reddy, Rajendar K. Mittapalli, Jing Yang, Donghua Yin
Summary: Combination therapies are commonly evaluated in the clinical development of oncology investigational agents, and the design needs to consider factors such as drug interactions and benefit/risk to study participants. This report proposes application scenarios for different trial designs and emphasizes the importance of generating robust exposure-response data for optimal dose selection.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Microbiology
Keith A. Rodvold, Justin Bader, Jon B. Bruss, Kamal Hamed
Summary: SPR206, a next-generation polymyxin, shows promise for treating multidrug-resistant (MDR) Gram-negative infections. A Phase 1 bronchoalveolar lavage (BAL) study was conducted to evaluate SPR206's safety and pharmacokinetics in healthy volunteers. The study demonstrates the pulmonary penetration of SPR206 and supports its further development for the treatment of serious infections caused by MDR Gram-negative pathogens.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Ivone Jimenez-Toro, Carlos A. Rodriguez, Andres F. Zuluaga, Julian D. Otalvaro, Hector Perez-Madrid, Omar Vesga
Summary: Combination therapy with ampicillin plus ceftriaxone is the first-line treatment for severe infections caused by Enterococcus faecalis, but the pharmacokinetic/pharmacodynamic index linked to its efficacy has not been defined yet, hindering dose optimization in clinical settings.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Mary E. E. Palmer, Lauren J. J. Andrews, Taylor C. C. Abbey, Ashley E. E. Dahlquist, Eric Wenzler
Summary: A deep understanding of pharmacokinetic and pharmacodynamic properties is crucial for optimizing drug use and increasing the chances of successful drug development. Recent advances in pharmacokinetic and pharmacodynamic studies have renewed confidence in their value and made them a fundamental component of drug development programs.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
A-Xi Shi, Qiang Qu, Hai-Hui Zhuang, Xin-Qi Teng, Wei-Xin Xu, Yi-Ping Liu, Yi-Wen Xiao, Jian Qu
Summary: Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in critically ill patients. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to poor clinical outcomes and the emergence of multidrug-resistant bacteria. Individualized dosing of antibiotics and various optimization strategies are needed for ARC patients.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Zhenwei Yu, Xiaofen Liu, Xiaoxing Du, Huiying Chen, Feng Zhao, Zhihui Zhou, Yu Wang, Yang Zheng, Phillip J. Bergen, Xi Li, Renhua Sun, Li Fang, Wanzhen Li, Yaxin Fan, Hailan Wu, Beining Guo, Jian Li, Yunsong Yu, Jing Zhang
Summary: This study evaluated the clinical pharmacokinetics/pharmacodynamics of polymyxin B in treating carbapenem-resistant K. pneumoniae bloodstream infections. The results showed that polymyxin B can effectively cure or improve patients with this infection, and PK/PD modeling can optimize the dosage and determine the breakpoints for treatment efficacy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Microbiology
Christian M. Gill, Elif Aktas, Wadha Alfouzan, Lori Bourassa, Adrian Brink, Carey-Ann D. Burnham, Rafael Canton, Yehuda Carmeli, Marco Falcone, Carlos Kiffer, Anna Marchese, Octavio Martinez, Spyros Pournaras, Harald Seifert, Abrar K. Thabit, Maria Virginia Villegas, Lars F. Westblade, David P. Nicolau
Summary: In this study, high in vitro potency of ceftazidime and cefepime among carbapenem-resistant Pseudomonas aeruginosa isolates was found, with 6 g/day required to achieve optimal pharmacodynamic profiles. These findings should be considered in the clinical setting and for the application of CLSI susceptibility breakpoints.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Courtney L. Luterbach, Hongqiang Qiu, Patrick O. Hanafin, Rajnikant Sharma, Joseph Piscitelli, Feng-Chang Lin, Jenni Ilomaki, Eric Cober, Robert A. Salata, Robert C. Kalayjian, Richard R. Watkins, Yohei Doi, Keith S. Kaye, Roger L. Nation, Robert A. Bonomo, Cornelia B. Landersdorfer, David van Duin, Gauri G. Rao
Summary: This study utilized a system-based approach to analyze the impact of colistin and ceftazidime-avibactam mono- or combination therapies on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infections. The findings suggest that combination therapy may improve bacterial killing. A unified model incorporating clinical, bacterial, and drug variables can be used to evaluate clinical outcomes.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Pharmacology & Pharmacy
J. Nicholas O'Donnell, Vibert Putra, Thomas P. Lodise
Summary: Treatment of patients with carbapenem-resistant Acinetobacter baumannii infections remains challenging, with limited viable treatment options and significant risk of nephrotoxicity associated with polymyxin therapy. New agents with clinically relevant activity against CRAB isolates and favorable toxicity profiles are urgently needed to address this urgent threat pathogen.
Article
Microbiology
N. Layios, C. Visee, V Mistretta, R. Denooz, N. Maes, J. Descy, F. Frippiat, S. Marchand, N. Gregoire
Summary: This article describes the population pharmacokinetics of temocillin administered via continuous infusion versus intermittent infusion in critically ill patients with pneumonia. The study also examines the penetration ratios of the drug in the epithelial lining fluid/plasma and determines the probability of achieving target concentrations for a range of MICs. The results show that continuous infusion provides better PK/PD indexes but still falls below recommended doses for systemic infections, unless the patient has moderate renal impairment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Kasper Norskov Kragh, Desiree Gijon, Ainhize Maruri, Alberto Antonelli, Marco Coppi, Mette Kolpen, Stephanie Crone, Chaitanya Tellapragada, Badrul Hasan, Stine Radmer, Corne de Vogel, Willem van Wamel, Annelies Verbon, Christian G. Giske, Gian Maria Rossolini, Rafael Canton, Niels Frimodt-Moller
Summary: The study demonstrates the efficacy of using microcalorimetry screening to predict additive or synergistic effects of combination treatment for MDR infections. Several antibiotic combinations showed synergistic or additive effects in vitro testing.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Immunology
John P. O'Donnell, Sujata M. Bhavnani
Summary: Sulbactam-durlobactam is a combination of beta-lactam and beta-lactamase inhibitor that is being developed for the treatment of Acinetobacter infections, including multidrug-resistant strains. Sulbactam has intrinsic antibacterial activity against Acinetobacter, but its effectiveness has been reduced by increasing beta-lactamase-mediated resistance. Durlobactam, a rationally designed beta-lactamase inhibitor, effectively restores susceptibility to resistant isolates when combined with sulbactam. This review discusses the pharmacokinetic/pharmacodynamic relationship of the combination in nonclinical infection models and aids in determining effective dose regimens for humans.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Iain J. Abbott, Elke van Gorp, Kelly L. Wyres, Steven C. Wallis, Jason A. Roberts, Joseph Meletiadis, Anton Y. Peleg
Summary: The effectiveness of oral fosfomycin in treating urinary tract infections caused by non-Escherichia coli uropathogens, including Klebsiella pneumoniae, is uncertain.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Karl Alex Hedin, Vanessa Emily Rees, Hongbin Zhang, Vibeke Kruse, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer
Summary: This study established a robust mouse model for studying the colonisation of Saccharomyces boulardii, finding that antibiotic treatment significantly increased the colonisation levels and duration of S. boulardii in mice. The findings suggest that the antibiotic cocktail used in the study is an advantageous tool for studying S. boulardii-based probiotics and advanced microbiome therapeutics.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Rajbharan Yadav, Siddharth Sukumaran, Tanja S. Zabka, Jinze Li, Amy Oldendorp, Gary Morrow, Arthur Reyes, Melissa Cheu, Jessica Li, Jeffrey J. Wallin, Siao Tsai, Laura Sun, Peiyin Wang, Diego Ellerman, Christoph Spiess, Andy Polson, Eric G. Stefanich, Amrita Kamath, Meric A. Ovacik
Summary: The study focuses on the impact of CD3 binding affinity on the pharmacokinetics of T cell-dependent bispecific antibodies. The results demonstrate that CD3 binding affinity affects the clearance rate of the antibody and may be related to the internalization rate of CD79b and the binding ability of CD3.
Review
Infectious Diseases
Kelly A. Cairns, Iain J. Abbott, Michael J. Dooley, Anton Y. Peleg, Trisha N. Peel, Andrew A. Udy
Summary: This study aimed to determine whether daptomycin therapeutic drug monitoring (TDM), including dose adjustment, improves the clinical outcomes of adult patients with Gram-positive infections. A systematic review found no studies exploring the efficacy of routine daptomycin TDM in comparison with fixed dosing regimens. Further well-designed, comparative studies are needed to determine the role of daptomycin TDM in patients with Gram-positive infections.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
Iain J. Abbott, Elke van Gorp, Hugh Cottingham, Nenad Macesic, Steven C. Wallis, Jason A. Roberts, Joseph Meletiadis, Anton Y. Peleg
Summary: The study found that high-dose oral ciprofloxacin therapy (750 mg 12 hourly) has good antibacterial activity against ceftriaxone-resistant Escherichia coli, especially with ciprofloxacin MIC <= 1 mg/L.
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)
Review
Microbiology
Kelly A. Cairns, Andrew A. Udy, Trisha N. Peel, Iain J. Abbott, Michael J. Dooley, Anton Y. Peleg
Summary: Vancomycin-resistant enterococci (VRE) are a common cause of bloodstream infections (BSIs) with high morbidity and mortality rates. The management of VRE BSI presents significant challenges, including drug dosing, resistance emergence, and optimal treatment strategies. Therapeutic drug monitoring (TDM) shows promise in predicting drug toxicity for VRE-active agents, but there is limited evidence for predicting antimicrobial efficacy for VRE BSIs. This article provides an overview of treatment options, the role of TDM in clinical infection management, and future challenges and perspectives.
CLINICAL MICROBIOLOGY REVIEWS
(2023)
Article
Microbiology
Micaela Mossop, Luca Robinson, Jhih-Hang Jiang, Anton Y. Peleg, Luke Blakeway, Nenad Macesic, Audrey Perry, Stephen Bourke, Fatima R. Ulhuq, Tracy Palmer
Summary: One third of CF patients in the UK are co-infected with both Staphylococcus aureus and Pseudomonas aeruginosa, which contribute to lung tissue destruction and respiratory failure. This study aims to characterize twenty-five clinical S. aureus isolates from CF patients, including those with mono- and coinfection with P. aeruginosa, using molecular and phenotypic tools.
JOURNAL OF MEDICAL MICROBIOLOGY
(2023)
Article
Pathology
Xenia Kostoulias, Christina C. Chang, Jessica Wisniewski, Iain J. Abbott, Helen Zisis, Amanda Dennison, Denis W. Spelman, Anton Y. Peleg
Summary: We investigated the effectiveness of ceftolozane-tazobactam (C/T) in a high-risk population for antimicrobial resistance, specifically patients with cystic fibrosis (CF) and lung transplantation (LTx). Out of 163 clinical Pseudomonas aeruginosa isolates collected from a tertiary hospital in Melbourne, Australia, 81.6% were susceptible to C/T. Among the multidrug resistant (MDR) and extensively drug resistant (XDR) isolates, C/T showed susceptibility in 88.3% and 28.1% of cases, respectively. In conclusion, C/T maintained its activity against a significant portion of MDR and XDR P. aeruginosa isolates from CF and post-LTx patients.
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)
Article
Computer Science, Interdisciplinary Applications
Yashpal Ramakrishnaiah, Nenad Macesic, Geoffrey I. Webb, Anton Y. Peleg, Sonika Tyagi
Summary: The adoption of electronic health records (EHRs) has created opportunities for predicting clinical outcomes and improving patient care. However, non-standardized data representations and anomalies present major challenges in digital health research. To address these challenges, we have developed EHR-QC, a tool with two modules: data standardization and preprocessing. We believe that the development and adoption of tools like EHR-QC are critical for advancing digital health.
JOURNAL OF BIOMEDICAL INFORMATICS
(2023)
Article
Chemistry, Medicinal
Rajbharan Yadav, Siddharth Sukumaran, Jeff Lutman, Mayur S. Mitra, Wendy Halpern, Tianhe Sun, Francesca Setiadi, Margaret Neighbors, X. Rebecca Sheng, Victor Yip, Ben-Quan Shen, Chang Liu, Lyrialle Han, Ayse Meric Ovacik, Yan Wu, Sara Glickstein, Rebecca Kunder, Joseph R. Arron, Lin Pan, Amrita V. Kamath, Eric G. Stefanich
Summary: MTBT1466A is a high-affinity TGF,B3-specific humanized IgG1 monoclonal antibody with reduced Fc effector function, currently being investigated in clinical trials as a potential anti-fibrotic therapy. The pharmacokinetics and pharmacodynamics of MTBT1466A were characterized in mice and monkeys, and the predicted behavior in humans was used to guide the selection of the first-in-human starting dose. The study provides insights into the PK/PD behavior of MTBT1466A in preclinical species and supports the translatability of the preclinical data into the clinic.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Microbiology
Yue Qu, David McGiffin, Lina Duque Sanchez, Thomas Gengenbach, Chris Easton, Helmut Thissen, Anton Y. Peleg
Summary: This study comprehensively assessed the anti-biofilm capability of the Carbothane driveline against leading microorganisms causing VAD driveline infections and explored its physicochemical characteristics. The Carbothane driveline demonstrated anti-biofilm activity, and the surface characteristics may explain its ability to inhibit biofilm formation.
Review
Microbiology
Jhih-Hang Jiang, David R. Cameron, Cara Nethercott, Marta Aires-de-Sousa, Anton Y. Peleg
Summary: This review focuses on the mechanisms that trigger the establishment and maintenance of current, dominant MRSA lineages across the globe. Factors that influence MRSA's ability to colonize and cause disease within a host are discussed, with an emphasis on colonization and niche adaptation. Understanding these mechanisms may lead to the development of targeted therapies.
CLINICAL MICROBIOLOGY REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Maytham Hussein, Labell J. M. Wong, Jinxin Zhao, Vanessa E. Rees, Rafah Allobawi, Rajnikant Sharma, Gauri G. Rao, Mark Baker, Jian Li, Tony Velkov
Summary: This study investigates the synergistic antibacterial activity of polymyxin B in combination with the antifungal caspofungin against Klebsiella pneumoniae, and analyzes the killing mechanisms of this combination.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)