Article
Pharmacology & Pharmacy
Xiangru Luo, Shiyi Wang, Dong Li, Jun Wen, Na Sun, Guangjun Fan
Summary: The study aimed to develop a pharmacokinetic model for tigecycline in critically ill patients and optimize dosing regimens. Results showed that APACHEII score and age significantly influenced the drug's clearance and distribution volume. The standard dose regimen often failed to achieve satisfactory therapeutic effects for critically ill patients.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Infectious Diseases
Noemie de Cacqueray, Deborah Hirt, Yi Zheng, Emmanuelle Bille, Pierre Louis Leger, Jerome Rambaud, Julie Toubiana, Anais Chosidow, Sophie Vimont, Delphine Callot, Laurent Chouchana, Agathe Beranger, Jean Marc Treluyer, Sihem Benaboud, Mehdi Oualha
Summary: The study aimed to build a population pharmacokinetic (PK) model for cefepime in critically ill children and optimize individual initial dosing regimens. The results showed that body weight and estimated glomerular filtration rate were associated with drug clearance. According to the simulations, continuous intravenous infusion of cefepime was more likely to achieve the PK target in patients with renal failure, while intermittent intravenous infusion was adequate for patients with normal or augmented renal clearance. Close therapeutic drug monitoring is necessary for cefepime treatment.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Article
Pharmacology & Pharmacy
Idoia Bilbao-Meseguer, Helena Barrasa, Eduardo Asin-Prieto, Ana Alarcia-Lacalle, Alicia Rodriguez-Gascon, Javier Maynar, Jose Angel Sanchez-Izquierdo, Goiatz Balziskueta, Maria Sanchez-Bayton Griffith, Nerea Quilez Trasobares, Maria Angeles Solinis, Arantxa Isla
Summary: This study evaluated the dosing of Levetiracetam in ICU patients with normal or augmented renal clearance (ARC), finding that CrCl influenced the drug clearance rate, with normal renal function patients requiring 500mg/8h or 1000mg/12h, and ARC patients needing higher doses.
Article
Microbiology
Mohammad H. Al-Shaer, Carolyn D. Philpott, Christopher A. Droege, Joshua D. Courter, Daniel P. Healy, Molly E. Droege, Neil E. Ernst, Eric W. Mueller, Charles A. Peloquin
Summary: Sepsis contributes to 50% of acute kidney injuries in the ICU, often requiring CRRT which impacts antimicrobial exposure. A cefepime PK model was built for CRRT ICU patients, showing good target attainment with intermittent infusion regimens at MICs <= 8 mg/l and extended infusion at MICs of 16 mg/l. This regimen may be considered for resistant bacterial infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Chao-Yang Chen, Min Xie, Jun Gong, Ning Yu, Ran Wei, Li-Li Lei, Si-Miao Zhao, Ruo-Ming Li, Xiu Dong, Xiang-Lin Zhang, Ying Zhou, Shuang-Ling Li, Yi-Min Cui
Summary: This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens. The study found that current standard doses may result in undertherapeutic concentrations and area under the curve (AUC), and a single dose of at least 12 mg/kg may be needed. Model-based simulations revealed the optimal dosing regimens for different renal functions. The importance of monitoring teicoplanin trough concentrations and AUC was emphasized.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Infectious Diseases
Peile Wang, Han Xing, Fei Zhang, Shaohua Liu, Yanqiu Lu, Xiaojian Zhang, Jing Yang, Tongwen Sun
Summary: This study analyzed the population pharmacokinetics of polymyxin B in patients undergoing continuous venovenous hemofiltration (CVVH) and proposed individualized dosing regimens for specific clinical scenarios. The results showed that CVVH significantly increased the clearance of polymyxin B, providing a basis for rational dosing in CVVH patients.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Infectious Diseases
Thanh Dinh, Hung N. Nguyen, Ba Hai Le, Thuy T. T. Nguyen, Huong T. L. Nguyen
Summary: This study developed a population pharmacokinetic model of imipenem for Vietnamese adult patients with severe illness, and suggested appropriate doses based on bacterial MIC values and the targeted PK/PD goals using Monte Carlo simulations.
INFECTION AND DRUG RESISTANCE
(2022)
Article
Microbiology
Jiao Xie, Qianting Yang, Xinyan Han, Yuzhu Dong, Tao Zhang, Youjia Li, Meixi Ji, Chenwei Liu, Yan Cai, Yan Wang
Summary: This study found that differences in pharmacokinetics/pharmacodynamics target attainment are often overlooked when antifungals are switched in critically ill patients. The results showed that triazoles at guideline-recommended doses could achieve target exposure for de-escalation treatment, while fluconazole and voriconazole performed poorly. Additionally, the achievement of target exposure for echinocandins decreased as body weight increased, with intermittent dosing strategy showing slightly higher CFR values in most simulations compared to conventional dosing strategy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Jae Ha Lee, Dong-Hwan Lee, Jin Soo Kim, Won-Beom Jung, Woon Heo, Yong Kyun Kim, Se Hun Kim, Tae-Hoon No, Kyeong Min Jo, Junghae Ko, Ho Young Lee, Kyung Ran Jun, Hye Sook Choi, Ji Hoon Jang, Hang-Jea Jang
Summary: This study found that the pharmacokinetics of meropenem in critically ill patients receiving ECMO were similar to those in patients without ECMO. Monte Carlo simulations have determined appropriate dosage regimens for meropenem, but dose adjustments may be needed for more aggressive targets.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Critical Care Medicine
Dhakrit Rungkitwattanakul, Weerachai Chaijamorn, Taniya Charoensareerat, Pratarn Charntrakarn, Orapan Khamkampud, Nakumporn Rattanaponpasert, Nattachai Srisawat, Sutthiporn Pattharachayakul
Summary: This study determined the optimal dosing of levofloxacin in critically ill patients receiving CRRT through mathematical modeling and simulation. It found that levofloxacin was not recommended as monotherapy for serious Gram-negative infections in this patient population, but was effective against Gram-positive infections.
JOURNAL OF CRITICAL CARE
(2021)
Article
Infectious Diseases
Ruiying Han, Dan Sun, Sihan Li, Jiaojiao Chen, Mengmeng Teng, Bo Yang, Yalin Dong, Taotao Wang
Summary: The study identified the optimal regimens of novel beta-lactam/beta-lactamase inhibitors (BLBLIs) for critically ill patients, showing that the effectiveness varied for different bacteria across ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam.
Article
Pharmacology & Pharmacy
Dong-Hwan Lee, Hyoung-Soo Kim, Sunghoon Park, Hwan-il Kim, Sun-Hee Lee, Yong-Kyun Kim
Summary: Limited studies have examined population pharmacokinetic models and optimal dosage regimens of meropenem for critically ill patients, with findings suggesting that prolonged infusion or high-dose regimens may be necessary when treating patients with certain infections.
Article
Pharmacology & Pharmacy
Femke de Velde, Brenda C. M. de Winter, Michael N. Neely, Jan Strojil, Walter M. Yamada, Stephan Harbarth, Angela Huttner, Teun van Gelder, Birgit C. P. Koch, Anouk E. Muller
Summary: Population pharmacokinetic modeling and simulation are used in antibiotic dosing optimization, with parametric and nonparametric models showing differences in predictive performance and target attainment probability calculations. The study found that while both models had satisfactory predictive performance for high eGFR values, they were insufficient for lower eGFR values, with the nonparametric model resulting in lower MICs due to higher estimated between-subject variability.
Article
Pharmacology & Pharmacy
Katie B. Landmesser, Justin A. Clark, David S. Burgess
Summary: Beta-Lactams are commonly used antibiotics in ICUs, but intermittent dosing of cefepime, meropenem, and piperacillin/tazobactam did not achieve >= 90% CFR for all organisms. Prolonged infusion of piperacillin/tazobactam and meropenem were the only regimens capable of achieving >= 90% CFR for specific pathogens in every ICU. Monte Carlo simulations incorporating local MIC distribution data can effectively predict optimal agent and dose selection within hospital systems to improve pharmacokinetic/pharmacodynamic optimization and clinical efficacy.
JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
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
Pharmacology & Pharmacy
Efthymios Manolis, Flora T. Musuamba, Kristin E. Karlsson
Summary: Selecting the right dose regimen for children and adolescents presents significant scientific, practical, and ethical challenges. Utilizing data from adults and considering the processes of maturation and growth are essential for pediatric dose selection. Therefore, study adaptations and model-informed approaches are crucial in characterizing dose exposure-response and selecting doses for children.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Microbiology
Albert Ruiz-Sorribas, Herve Poilvache, Francoise Van Bambeke
Summary: This study investigated the activity of different drugs against interkingdom biofilms using a three-species biofilm model. The results showed limited effectiveness of the drugs when used alone, but increased effects were observed when the drugs were used in combination, particularly against three-species biofilms. Additionally, different antibiotics showed better efficacy against different bacterial species. These findings were further confirmed by confocal microscopy images.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Chemistry, Medicinal
Gang Wang, Jean-Michel Brunel, Hector Rodriguez-Villalobos, Jean-Michel Bolla, Francoise Van Bambeke
Summary: NV716 can enhance the activity of antibiotics against difficult-to-treat Gram-negative bacteria by interacting with the bacterial outer membrane, resulting in increased accumulation of antibiotics inside bacteria. It can also increase the activity of antibiotics against intracellular infection and biofilms, without toxicity to eukaryotic cells at sub-MIC concentrations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Infectious Diseases
Angele Modupe Dohou, Valentina Oana Buda, Loconon Achille Yemoa, Severin Anagonou, Francoise Van Bambeke, Thierry Van Hees, Francis Moise Dossou, Olivia Dalleur
Summary: The excessive use and misuse of antibiotics have a significant impact on the global numbers of antibiotic-resistant pathogens and commensal bacteria. In Benin, there are various problems with antibiotic use during caesarean sections, highlighting the need for a national policy to improve antibiotic usage.
Article
Infectious Diseases
Angele Modupe Dohou, Valentina Oana Buda, Severin Anagonou, Francoise Van Bambeke, Thierry Van Hees, Francis Moise Dossou, Olivia Dalleur
Summary: A low adherence to recommendations on antibiotic prophylaxis has been reported worldwide. In Benin, despite the provision of free kits containing necessary supplies and antibiotics for prophylaxis during cesarean sections, the level of antibiotic prophylaxis achievement remains low. A study in three hospitals found that healthcare professionals had limited knowledge and various determinants, such as suboptimal patient health status, low confidence in antibiotics, disagreement with the policy, inappropriate infrastructures and limited financial resources, poor management of the policy at the central level, and patient refusal to buy antibiotics, explain the poor practices. Policymakers must consider these determinants to improve antibiotic prophylaxis and reduce antimicrobial resistance.
Article
Infectious Diseases
Perrin Ngougni Pokem, Xavier Wittebole, Christine Collienne, Hector Rodriguez-Villalobos, Paul M. Tulkens, Laure Elens, Francoise Van Bambeke, Pierre-Francois Laterre
Summary: This study investigated the pharmacokinetics of temocillin in plasma and ascitic fluid, and performed dosing simulations. The current dosing regimen achieved the target concentration in plasma, but not in ascitic fluid. Adjusting the dosing regimen might allow for target concentration attainment in ascitic fluid, but further evaluation is needed for safety and efficacy.
Review
Pharmacology & Pharmacy
David De Bels, Evelyne Maillart, Francoise Van Bambeke, Sebastien Redant, Patrick M. Honore
Summary: Invasive candidiasis or candidemia is a severe global infection with high mortality, and therapeutic failure is common due to the emergence of resistant strains and new species. This review discusses the current antifungal drugs used for candidiasis and the advancements made in new formulations, derivatives, and repurposed drugs. The results from ongoing and future clinical trials will be crucial in determining the efficacy and interest of these drugs in the treatment of candidiasis.
EXPERT OPINION ON EMERGING DRUGS
(2022)
Article
Infectious Diseases
Maria Angeles Melendez-Carmona, Mikel Mancheno-Losa, Albert Ruiz-Sorribas, Irene Munoz-Gallego, Esther Viedma, Fernando Chaves, Francoise Van Bambeke, Jaime Lora-Tamayo
Summary: There is significant variability in the response of biofilm-embedded Staphylococcus aureus to levofloxacin and rifampicin. A lower range response, combined with other factors, could be responsible for treatment failure.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Biology
Gang Wang, Jean-Michel Brunel, Matthias Preusse, Negar Mozaheb, Sven D. Willger, Gerald Larrouy-Maumus, Pieter Baatsen, Susanne Haeussler, Jean-Michel Bolla, Francoise Van Bambeke
Summary: The polyaminoisoprenyl compound NV716 re-sensitizes Pseudomonas aeruginosa to antibiotics by permeabilizing the outer membrane and increases the activity of antibiotics on biofilms.
COMMUNICATIONS BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Flora T. Musuamba, S. Y. Amy Cheung, Pieter Colin, Elin H. Davies, Jeffrey S. Barret, Francesco Pappalardo, Michael Chappell, Jean-Michel Dogne, Adriana Ceci, Oscar Della Pasqua, Ine S. Rusten
Summary: The benefit/risk balance is the most important question when considering market access for medicinal products. This assessment involves evaluating efficacy, safety, dose selection, pharmacology, and drug quality. However, there is currently no systematic approach to assess and establish the acceptability of alternative methods and data sources, leading to regulatory skepticism toward new data types and methods. To mitigate uncertainties in efficacy and safety characterization, a data-knowledge backbone is needed. This white paper proposes an ecosystem based on a repository, high-quality standards, and credibility assessment for better regulatory decision making.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Correction
Microbiology
Albert Ruiz-Sorribas, Herve Poilvache, Nur Hidayatul Nazirah Kamarudin, Annabel Braem, Francoise Van Bambeke
MICROBIOLOGY SPECTRUM
(2023)
Editorial Material
Infectious Diseases
Francoise Van Bambeke, Sebastian Wicha, Paul M. Tulkens, Markus Zeitlinger
Article
Microbiology
Frederic Peyrusson, Tiep Khac Nguyen, Tome Najdovski, Francoise Van Bambeke
Summary: This study investigates the effect of reactive oxygen species (ROS) on the dormancy depth of intracellular S. aureus persisters in host cells. It is found that host ROS can induce variable dormant states in persisters and the level of oxidative stress determines the capacity for resuscitation. The results highlight the importance of understanding the interplay between ROS, ATP depletion, and dormancy state in S. aureus infections.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Albert Ruiz-Sorribas, Herve Poilvache, Nur Hidayatul Nazirah Kamarudin, Annabel Braem, Francoise Van Bambeke
Summary: Biofilms are resistant to antimicrobials, but hydrolytic enzymes can reduce their biomass. Subtilisin A and lyticase are the most effective enzymes against interkingdom biofilms. Combining enzymes with antimicrobials further reduces the biomass.
MICROBIOLOGY SPECTRUM
(2022)
Meeting Abstract
Pharmacology & Pharmacy
T. M. Nanga, S. Bouriah, J. B. Woillard, A. Rousseau, P. Marquet, F. T. Musuamba, A. Premaud
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2021)