Article
Ecology
Thomas James O'Brien, Wendy Figueroa, Martin Welch
Summary: The presence of diverse polymicrobial communities in the airways of individuals with cystic fibrosis can hinder the effectiveness of antibiotic treatment. A study showed that growth in a polymicrobial environment protects the target microorganism from the effects of specific antimicrobial agents. This decreased efficacy is found to have both physiological and genetic components.
Article
Microbiology
Mona Shaban E. M. Badawy, Walid F. Elkhatib, Rania I. Shebl
Summary: This study evaluated the anti-biofilm potentials of various antibiotics alone and in combination against biofilm-forming carbapenem-resistant Pseudomonas aeruginosa (CRPA). The results showed that colistin exhibited the strongest anti-biofilm activity, followed by gentamicin and meropenem, while ceftazidime had the least activity. Combination therapy showed synergistic effects. The simulated pharmacodynamic modeling confirmed the synergistic anti-biofilm activity observed in vitro.
ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS
(2023)
Article
Infectious Diseases
Eva Benavent, Marta Ulldemolins, Cristina El Haj, Raul Rigo-Bonnin, Heidi Yu, Lynn Wang, Hasini Wickremasinghe, Javier Ariza, Oscar Murillo
Summary: This study aimed to analyze the PK/PD indices of meropenem predicting anti-biofilm efficacy against meropenem-susceptible and meropenem-resistant strains of Pseudomonas aeruginosa. The results showed that f%T >MIC was the PK/PD index that best correlated with the anti-biofilm efficacy of meropenem. Using the extended infusion regimen of meropenem can better recover bactericidal activity in monotherapy, including activity against meropenem-resistant P. aeruginosa.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
Van Thi Khanh Nguyen, Preecha Montakantikul, Pramote Tragulpiankit, Jantana Houngsaitong, Mohd Fazli Shuib
Summary: This study evaluated various colistin dosing regimens against Pseudomonas aeruginosa infection in critically ill patients using Monte Carlo simulations based on pharmacokinetic and pharmacodynamic parameters. It found that higher total daily doses and fractionated dosing regimens may be effective in difficult-to-treat cases, while less aggressive dosing may be suitable for empirical treatment in settings with low MIC50/90.
Article
Microbiology
Luisa Sorli, Sonia Luque, Jian Li, Adela Benitez-Cano, Xenia Fernandez, Nuria Prim, Victoria Vega, Joan Gomez-Junyent, Inmaculada Lopez-Montesinos, Silvia Gomez-Zorrilla, M. Milagro Montero, Santiago Grau, Juan Pablo Horcajada
Summary: This study investigated the relationship between colistin plasma concentrations and clinical outcomes in patients with hospital-acquired pneumonia caused by extensively drug-resistant Pseudomonas aeruginosa. The findings showed that higher colistin exposure did not improve clinical outcomes.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Lingbo Wang, Ying Zhang, Yishuai Lin, Jianming Cao, Chunyan Xu, Liqiong Chen, Yaran Wang, Yao Sun, Xiangkuo Zheng, Yong Liu, Tieli Zhou
Summary: P. aeruginosa is a widespread bacterium associated with life-threatening infections. Improper use of antibiotics has led to the emergence of multidrug-resistant strains, including colistin-resistant strains. This study demonstrates that colistin/resveratrol combination therapy has a strong synergistic effect in eradicating colistin-resistant P. aeruginosa strains and their biofilms.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Zinan Zhang, Dominic Ortega, Anthony Rush, Lauren R. Blankenship, Zi Jun Cheng, Rebecca E. Moore, Minh L. N. Tran, Lucero G. Sandoval, Kareem Aboulhosn, Seiichiro Watanabe, Kendra S. Cortez, David H. Perlman, Martin F. Semmelhack, Laura C. Miller Conrad
Summary: Newly developed antipyocyanin compounds not only have potential antivirulence effects, but may also act as antibiotic adjuvants to amplify bactericidal activity. These compounds could represent a first-in-class antibiotic adjuvant therapy, widening the therapeutic index and strengthening our arsenal against Pseudomonas aeruginosa infections.
ACS INFECTIOUS DISEASES
(2021)
Article
Microbiology
Saoirse Disney-McKeethen, Seokju Seo, Heer Mehta, Karukriti Ghosh, Yousif Shamoo
Summary: Antibiotic resistance is a global health crisis, and understanding the evolutionary trajectories leading to increased resistance is crucial for developing clinical diagnostics and discovering new drug targets. Researchers found that adaptive mutations to phoQ were more successful than pmrB in increasing resistance to colistin, a commonly used antibiotic. The study also revealed that the oxygen concentration gradients within the microdroplet emulsions favored changes to the PhoP/PhoQ pathway, which is consistent with the microaerobic conditions found in the lungs of cystic fibrosis patients.
Article
Microbiology
Jingchun Kong, Yue Wang, Zhuocheng Yao, Yishuai Lin, Yi Zhang, Yijia Han, Tieli Zhou, Jianzhong Ye, Jianming Cao
Summary: In this study, the combination of colistin and eugenol was found to have a significant synergistic antibacterial effect against colistin-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. The combination increased membrane permeability and caused membrane damage, inhibiting bacteria synergistically. Eugenol was non-toxic to cells and the combination was effective in vivo. These findings suggest that the colistin/eugenol combination may be a viable treatment option for colistin-resistant bacterial infections.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Yuhang Wang, Chunsun Li, Jin Wang, Nan Bai, Huan Zhang, Yulong Chi, Yun Cai
Summary: In this study, the in vitro and in vivo efficacy of colistin-based combinations against Pseudomonas aeruginosa (PA) biofilm were evaluated. The results showed that colistin combined with levofloxacin or amikacin could effectively eradicate the biofilm. This study provided a new treatment regimen for PA biofilm infection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Infectious Diseases
Jessica Howard-Anderson, Michelle Davis, Alexander M. Page, Chris W. Bower, Gillian Smith, Jesse T. Jacob, Dan Andersson, David S. Weiss, Sarah W. Satola
Summary: This study investigated the prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and its association with clinical outcomes. The results showed that colistin heteroresistance was present in up to 26% of CRPA patients, but it did not have a significant impact on 90-day mortality.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Aline Munting, Jean Regina, Jose Damas, Loic Lhopitallier, Antonios Kritikos, Benoit Guery, Laurence Senn, Benjamin Viala
Summary: We evaluated the impact of the 10th version of the European Committee on Antimicrobial Susceptibility Testing on meropenem prescription for Pseudomonas aeruginosa infections and found that the update was associated with an increased likelihood of meropenem prescription for these infections.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Article
Infectious Diseases
Iris K. Minichmayr, Suzanne Kappetein, Margreke J. E. Brill, Lena E. Friberg
Summary: In this study, the impact of differently shaped clinical pharmacokinetic profiles of meropenem on the growth and killing patterns of Pseudomonas aeruginosa was investigated using a semi-mechanistic PKPD model and a PK/PD index-based approach. Continuous infusion plus loading dose and 3-hour infusions were found to be superior to standard 0.5-hour infusions in certain scenarios.
Article
Infectious Diseases
Miki Takemura, Mark G. Wise, Meredith A. Hackel, Daniel F. Sahm, Yoshinori Yamano
Summary: This study evaluated the in vitro antibacterial activity of siderophore cephalosporin cefiderocol against MBL-producing clinical isolates. The results showed that cefiderocol exhibited potent in vitro activity against MBL-producing strains of different bacterial species.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Microbiology
Yue Wang, Jingchun Kong, Xiaodong Zhang, Yan Liu, Zeyu Huang, Lu Yuan, Ying Zhang, Jianming Cao, Lijiang Chen, Yong Liu, Tieli Zhou
Summary: The emergence and spread of multi-drug resistant strains globally have raised concerns, especially with the re-emergence of colistin-resistant bacteria. A study has found that the combination of plumbagin and colistin effectively inhibits colistin-resistant P. aeruginosa, showing promising results in both in vitro and in vivo settings. This combination not only prevents biofilm formation but also eradicates mature biofilms, providing a potential treatment option for COL-R PA infections.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Oncology
Ana-Marija Grisic, Wenyuan Xiong, Lenaig Tanneau, Siv Jonsson, Lena E. Friberg, Mats O. Karlsson, Haiqing Dai, Jenny Zheng, Pascal Girard, Akash Khandelwal
Summary: This study developed a semi-mechanistic pharmacokinetic-tumor growth dynamics model to investigate the exposure response relationship for avelumab and the interaction between PK and TGD. The PK of avelumab was described by a two-compartment model with a positive association between clearance and tumor size, without additional time-varying clearance identified. TGD was described by first-order tumor growth/shrinkage rates, with the tumor shrinkage rate decreasing exponentially over time and negatively correlated with drug concentration.
CLINICAL CANCER RESEARCH
(2022)
Article
Infectious Diseases
Aikaterini Gkoufa, Tomas Sou, Ilias Karaiskos, Christina Routsi, Yu-Wei Lin, Mina Psichogiou, Spyros Zakynthinos, Helen Giamarellou, Jian Li, Lena E. Friberg
Summary: This study assessed the pharmacokinetics of nebulised colistin methanesulfonate (CMS) for the treatment of ventilator-associated pneumonia (VAP) and found that nebulised CMS can achieve high concentrations of formed colistin in the epithelial lining fluid (ELF) while maintaining lower concentrations in plasma.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Infectious Diseases
Iris K. Minichmayr, Vincent Aranzana-Climent, Lena E. Friberg
Summary: Pharmacokinetic/pharmacodynamic (PKPD) models are valuable tools for characterizing and translating antibiotic effects. These models provide a more accurate description of the time course of antibiotic effects, considering mechanistic knowledge of pathogens and drugs. This review provides a comprehensive overview of previously published PKPD models, highlighting their details and main development purposes.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Infectious Diseases
Chenyan Zhao, Anna Chirkova, Staffan Rosenborg, Rodrigo Palma Villar, Johan Lindberg, Sven N. Hobbie, Lena E. Friberg
Summary: The aim of this study was to conduct a population pharmacokinetic analysis of apramycin and predict an efficacious dose based on data from the Phase I trial. The results showed that an anticipated efficacious dose of 30 mg/kg daily could be used for further Phase II clinical trials.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Iris K. Minichmayr, Suzanne Kappetein, Margreke J. E. Brill, Lena E. Friberg
Summary: In this study, the impact of differently shaped clinical pharmacokinetic profiles of meropenem on the growth and killing patterns of Pseudomonas aeruginosa was investigated using a semi-mechanistic PKPD model and a PK/PD index-based approach. Continuous infusion plus loading dose and 3-hour infusions were found to be superior to standard 0.5-hour infusions in certain scenarios.
Article
Medicine, Research & Experimental
Maddalena Centanni, Abel Thijs, Ingrid Desar, Mats O. Karlsson, Lena E. Friberg
Summary: This study investigated the factors influencing blood pressure measurements and compared different measurement techniques using a pharmacokinetic-pharmacodynamic modeling framework. The study found that circadian changes, as well as random intra-day and inter-day variability, were the largest sources of within-individual variation in blood pressure. Continuous home-based measurements taken at a consistent time or within a limited time frame were found to provide the most consistent blood pressure estimates.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Thomas G. H. Kempen, Anton N. Hedman, Nermin Hadziosmanovic, Karl-Johan Lindner, Hakan Melhus, Elisabet I. Nielsen, Johanna Sulku, Ulrika Gillespie
Summary: The aim of this study was to identify risk factors for drug-related readmissions in older patients and assess the preventability of these revisits. A post hoc analysis was conducted on a randomized clinical trial involving older patients at four hospitals in Sweden. The study found that risk factors for drug-related readmissions in older hospitalized patients included age, previous hospital visits, medication use, and multiple diseases. Potentially preventable drug-related readmissions can be prevented through adequate pharmacotherapy and continuity of care.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Sreenath M. Krishnan, Lena E. Friberg, Francois Mercier, Rong Zhang, Ben Wu, Jin Y. Jin, Tien Hoang, Marcus Ballinger, Rene Bruno, Mats O. Karlsson
Summary: This study used data from the IMpower131 study to establish a multistate model framework and investigate the influence of second-line immunotherapies on overall survival analysis. The study found that high PD-L1 expression was associated with a decreased risk of progression, while the presence of liver metastasis indicated a high risk of disease progression. The simulations showed that the addition of atezolizumab to the treatment regimen improved patient survival significantly.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Robin J. Svensson, Qing Xi Ooi, Lena E. Friberg, Narendra Maharaj, Pramod Kumar Reddy, Luis Lopez-Lazaro, Emma Hansson
Summary: Dr. Reddy's Laboratories rituximab (DRL-RI) is a rituximab biosimilar that showed similar pharmacokinetic, pharmacodynamic, efficacy, safety, and immunogenicity profiles to the reference medicinal product MabThera. The study also indicated that tumor size may influence the pharmacokinetics of rituximab, but does not affect the evaluation of the drug product.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Han Liu, Ana-Marija Milenkovic-Grisic, Sreenath M. Krishnan, Siv Joensson, Lena E. Friberg, Pascal Girard, Karthik Venkatakrishnan, Yulia Vugmeyster, Akash Khandelwal, Mats O. Karlsson
Summary: This study applies the multistate pharmacometric modeling and simulation framework to investigate the dose optimization of bintrafusp alfa in non-small cell lung cancer patients. A six-state multistate model is developed to describe the endpoints data, and the results suggest that the 1200 mg dose may lead to longer median overall survival compared to the 500 mg dose.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(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
Pharmacology & Pharmacy
Javier Sanchez, Christina Claus, Rosmarie Albrecht, Brenda C. Gaillard, Joana Marinho, Christine Mcintyre, Tamara Tanos, Axel Boehnke, Lena E. Friberg, Siv Joensson, Nicolas Frances
Summary: This study characterizes the pharmacology of FAP-4-1BBL as a bispecific antibody and predicts the dose range for trimeric complex formation when combined with the T-cell engager cibisatamab using mathematical modeling techniques. It highlights the importance of mathematical modeling based on in vitro data in aiding dose selection.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)