Article
Pharmacology & Pharmacy
Sacha Sarfati, Julien Wils, Timothee Lambert, Celine Mory, Laurent Imbert, Gilles Gargala, Helene Morisse-Pradier, Fabien Lamoureux
Summary: This study evaluated the feasibility and utility of therapeutic drug monitoring (TDM) of voriconazole concentration in sputum for patients treated for pulmonary aspergillosis. The results showed a correlation between sputum and plasma levels of voriconazole, and an equation was established to predict voriconazole concentration in plasma from sputum.
Article
Infectious Diseases
Julie Gorham, Fabio S. Taccone, Maya Hites
Summary: Obesity is associated with increased risks of comorbidities, postoperative infections, and nosocomial infections. The pharmacokinetics and pharmacodynamics of antibiotics are affected by obesity, leading to increased risks of antibiotic therapy failure and toxicity. Precision dosing of antibiotics using therapeutic drug monitoring may improve the management of critically ill obese patients with infections.
Article
Infectious Diseases
Anette Veringa, Roger J. Bruggemann, Lambert F. R. Span, Bart J. Biemond, Mark G. J. de Boer, Edwin R. van den Heuvel, Saskia K. Klein, Doris Kraemer, Monique C. Minnema, Niek H. J. Prakken, Bart J. A. Rijnders, Jesse J. Swen, Paul E. Verweij, Marielle J. Wondergem, Paula F. Ypma, Nicole Blijlevens, Jos G. W. Kosterink, Tjip S. van der Werf, Jan-Willem C. Alffenaar
Summary: This study investigated whether TDM-guided voriconazole treatment is superior to standard treatment for invasive aspergillosis. The results showed no significant difference in treatment outcome and adverse reactions between the TDM and non-TDM groups, but a higher proportion of voriconazole concentrations within the acceptable range were found in the TDM group.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Pharmacology & Pharmacy
Irene Garcia-Garcia, Irene Dapia, Jaime Montserrat, Lucia Martinez de Soto, David Bueno, Lucia Diaz, Javier Queiruga, Amelia Rodriguez Mariblanca, Pilar Guerra-Garcia, Elena Ramirez, Jesus Frias, Antonio Perez Martinez, Antonio J. Carcas-Sansuan, Alberto M. Borobia
Summary: The study found that for immunocompromised patients treated with voriconazole, pre-treating with CYP2C19 gene typing and adjusting doses according to guidelines can increase the proportion of patients reaching therapeutic target concentrations, especially for CYP2C19 Normal Metabolizers/Intermediate Metabolizers and Rapid Metabolizers/Ultrarapid Metabolizers.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Microbiology
Sana Jemel, Jacques Guillot, Kalthoum Kallel, Gregory Jouvion, Elise Brisebard, Eliane Billaud, Vincent Jullien, Francoise Botterel, Eric Dannaoui
Summary: This study evaluated the efficacy of VRZ in a G. mellonella model infected with azole-susceptible or azole-resistant A. fumigatus isolates, showing that VRZ was more effective against susceptible isolates. G. mellonella was found to be a suitable model for testing antifungal agents against A. fumigatus.
Review
Pharmacology & Pharmacy
Matylda Resztak, Joanna Sobiak, Andrzej Czyrski
Summary: This review discusses the importance of therapeutic drug monitoring (TDM) for voriconazole (VCZ), mycophenolic acid (MPA), and vancomycin (VAN) in pediatric patients, emphasizing the need for individualized dosing in antifungal therapy and bactericidal treatment. Pharmacokinetic variability poses challenges in maintaining therapeutic drug concentrations, particularly in achieving effective levels of VCZ in children with invasive fungal infections. The role of TDM for mycophenolate mofetil (MMF) and vancomycin in pediatric patients is still under debate, with proposed approaches beyond pharmacokinetics including pharmacodynamics and pharmacogenetics.
Article
Microbiology
Iker Falces-Romero, Jesus Mingorance, Julio Garcia-Rodriguez, Emilio Cendejas-Bueno
Summary: This study presented a proof-of-concept for using MALDI Biotyper to detect and monitor levels of voriconazole in human serum, demonstrating good reproducibility. The results suggest a new potential application of MALDI Biotyper in therapeutic drug monitoring.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Wenbo Ren, Lei Yin, Gaixia Zhang, Taiyu Zhai, Jing Huang
Summary: This study developed and validated a high-performance liquid chromatography tandem mass spectrometry cubed (HPLC-MS3) method for quantifying voriconazole in human plasma. The method showed high accuracy and stability, and compared to HPLC-MRM, HPLC-MS3 had a higher signal-to-noise ratio and response without significant differences in results. The HPLC-MS3 method was successfully applied to monitor voriconazole therapeutic drug monitoring (TDM) in patients, confirming the implementation of dosing guidelines and the effectiveness of treatment.
Article
Pharmacology & Pharmacy
Tingting Chen, Shuifa Wu, Huatang Zhang, Qingquan Zhang, Zhiqiang Lin
Summary: This study retrospectively analyzed voriconazole therapeutic drug monitoring (TDM) in AIDS patients. It found that the compliance rate of trough concentration was low after the initial dosing regimen, and drug-drug interactions and hypoalbuminemia were important factors affecting trough concentration. TDM improved the attainment of target concentrations and guided individualized medication of voriconazole in AIDS patients.
LATIN AMERICAN JOURNAL OF PHARMACY
(2022)
Article
Immunology
Kaitlin Benedict, Jeremy A. W. Gold, Susan E. Beekmann, Philip M. Polgreen, Mitsuru Toda, Dallas J. Smith
Summary: A survey of 523 infectious disease specialists found that a significant number of experts utilize antifungal therapeutic drug monitoring during treatment, but the usage is lower during prophylaxis. The long turnaround times for testing and logistical difficulties are common barriers to the implementation of therapeutic drug monitoring.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Pharmacology & Pharmacy
Lin Hu, Qi Huang, Shiqiong Huang, Zeying Feng
Summary: The study evaluated the factors that influence voriconazole plasma trough concentrations in Chinese pediatric patients and provided research data for optimizing voriconazole dosing. The CYP2C19 phenotype significantly influences voriconazole plasma trough concentrations, and the recommended maintenance dose may not be suitable for Chinese patients. Adjusting voriconazole administration based on the age of pediatric patients and the presence of CYP2C19 polymorphisms can increase the likelihood of achieving the therapeutic range.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Dermatology
Christelle Boglione-Kerrien, Jeff Morcet, Lucie-Marie Scailteux, Francois Benezit, Christophe Camus, Jean-Baptiste Mear, Jean-Pierre Gangneux, Eric Bellissant, Camille Tron, Marie-Clemence Verdier, Florian Lemaitre
Summary: This study aimed to implement routine measurement of voriconazole N-oxide (NOX) concentrations, describe the metabolic ratio (MR), and propose a suggested dosage-adjustment algorithm for therapeutic drug monitoring (TDM) of patients treated with voriconazole (VRC). The MR based on NOX proved to be useful for interpretation and clinical decision-making, especially for complex patients. A dosing algorithm was suggested based on the results.
Review
Pharmacology & Pharmacy
Yoshio Takesue, Yuki Hanai, Kazutaka Oda, Yukihiro Hamada, Takashi Ueda, Toshihiko Mayumi, Kazuaki Matsumoto, Satoshi Fujii, Yoshiko Takahashi, Yoshitsugu Miyazaki, Toshimi Kimura
Summary: Increased adverse effects of Voriconazole, an antifungal drug, are observed in Asians due to the high rate of poor metabolizers. This therapeutic drug monitoring (TDM) guideline provides recommendations according to ethnic group.
CLINICAL THERAPEUTICS
(2022)
Article
Microbiology
Jose Maria Valle-T-Figueras, Berta Renedo Miro, Maria Isabel Benitez Carabante, Cristina Diaz-de-Heredia, Jaume Vima Bofarull, Natalia Mendoza-Palomar, Maria Teresa Martin-Gomez, Pere Soler-Palacin
Summary: Voriconazole plasma concentrations in children are highly variable, especially in patients aged 5-12 years. The new dosing recommendations have led to an increased rate of adequate PC in therapeutic drug monitoring, but still a portion falls outside the therapeutic range. Factors influencing PC include severe hypoalbuminemia and elevated C-reactive protein levels.
Article
Microbiology
Suresh Ambati, Emma C. Ellis, Tuyetnhu Pham, Zachary A. Lewis, Xiaorong Lin, Richard B. Meagher
Summary: The use of Dectin-2-targeted liposomes to deliver amphotericin B has shown significant efficacy in reducing fungal burden at infection sites in the lungs and prolonging survival in mice with pulmonary aspergillosis. This targeted delivery system has the potential to improve treatment outcomes for various fungal diseases by enhancing the efficacy of antifungal drugs at lower doses.
Article
Biochemistry & Molecular Biology
Yapeng Su, Dan Yuan, Daniel G. Chen, Rachel H. Ng, Kai Wang, Jongchan Choi, Sarah Li, Sunga Hong, Rongyu Zhang, Jingyi Xie, Sergey A. Kornilov, Kelsey Scherler, Ana Jimena Pavlovitch-Bedzyk, Shen Dong, Christopher Lausted, Inyoul Lee, Shannon Fallen, Chengzhen L. Dai, Priyanka Baloni, Brett Smith, Venkata R. Duvvuri, Kristin G. Anderson, Jing Li, Fan Yang, Caroline J. Duncombe, Denise J. McCulloch, Clifford Rostomily, Pamela Troisch, Jing Zhou, Sean Mackay, Quinn DeGottardi, Damon H. May, Ruth Taniguchi, Rachel M. Gittelman, Mark Klinger, Thomas M. Snyder, Ryan Roper, Gladys Wojciechowska, Kim Murray, Rick Edmark, Simon Evans, Lesley Jones, Yong Zhou, Lee Rowen, Rachel Liu, William Chour, Heather A. Algren, William R. Berrington, Julie A. Wallick, Rebecca A. Cochran, Mary E. Micikas, Terri Wrin, Christos J. Petropoulos, Hunter R. Cole, Trevan D. Fischer, Wei Wei, Dave S. B. Hoon, Nathan D. Price, Naeha Subramanian, Joshua A. Hill, Jennifer Hadlock, Andrew T. Magis, Antoni Ribas, Lewis L. Lanier, Scott D. Boyd, Jeffrey A. Bluestone, Helen Chu, Leroy Hood, Raphael Gottardo, Philip D. Greenberg, Mark M. Davis, Jason D. Goldman, James R. Heath
Summary: Post-acute sequelae of COVID-19 (PASC) is an emerging global crisis, and the quantifiable risk factors and biological associations are not well understood. In this study, a deep multi-omic investigation was conducted on 309 COVID-19 patients, and four PASC-anticipating risk factors were identified at the time of initial diagnosis. The study also observed changes in immune states during recovery from COVID-19.
Article
Immunology
Anna Bershteyn, Angela M. Dahl, Tracy Q. Dong, Meagan E. Deming, Connie L. Celum, Helen Y. Chu, Angelica C. Kottkamp, Alexander L. Greninger, Risa M. Hoffman, Keith R. Jerome, Christine M. Johnston, Patricia J. Kissinger, Raphael J. Landovitz, Miriam K. Laufer, Alfred Luk, Kathleen M. Neuzil, Michael K. Paasche-Orlow, Robert A. Pitts, Mark D. Schwartz, Helen C. Stankiewicz Karita, Lorna E. Thorpe, Anna Wald, Crystal Y. Zheng, Mark H. Wener, Ruanne Barnabas, Elizabeth R. Brown
Summary: Symptom definitions for COVID-19 rarely consider symptom severity. This study found that requiring the presence of at least one moderate or severe symptom reduced the sensitivity of predicting SARS-CoV-2 shedding, but increased specificity.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Amanda M. Casto, Julia H. Rogers, Amy C. Link, Michael Boeckh, Michael L. Jackson, Timothy M. Uyeki, Janet A. Englund, Lea M. Starita, Helen Y. Chu
Summary: Using genomic data, the study analyzed the transmission of SARS-CoV-2 in 8 shelters in King County, Washington. The results suggest that intrashelter transmission is common, but there is no evidence of widespread transmission of shelter-related viruses into the general population.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Immunology
Meagan E. Deming, Tracy Q. Dong, Vaidehi Agrawal, Margaret G. Mills, Meei-Li W. Huang, Alexander L. Greninger, Keith R. Jerome, Mark H. Wener, Michael K. Paasche-Orlow, Patricia Kissinger, Alfred Luk, Risa M. Hoffman, Jenell Stewart, Angelica C. Kottkamp, Anna Bershteyn, Helen Y. Chu, Helen C. Stankiewicz Karita, Christine M. Johnston, Anna Wald, Ruanne Barnabas, Elizabeth R. Brown, Kathleen M. Neuzil
Summary: By studying SARS-CoV-2 swab samples, we have identified a diagnostic RNA threshold that is correlated with detectable subgenomic RNA, which can accurately identify viral replication. Our research shows that the majority of samples can detect subgenomic RNA when the diagnostic RNA viral load reaches a certain threshold. The trajectories of diagnostic RNA and subgenomic RNA detection differ, with the latter having a shorter detection duration.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Multidisciplinary Sciences
Elisabetta Cameroni, John E. Bowen, Laura E. Rosen, Christian Saliba, Samantha K. Zepeda, Katja Culap, Dora Pinto, Laura A. VanBlargan, Anna De Marco, Julia di Iulio, Fabrizia Zatta, Hannah Kaiser, Julia Noack, Nisar Farhat, Nadine Czudnochowski, Colin Havenar-Daughton, Kaitlin R. Sprouse, Josh R. Dillen, Abigail E. Powell, Alex Chen, Cyrus Maher, Li Yin, David Sun, Leah Soriaga, Jessica Bassi, Chiara Silacci-Fregni, Claes Gustafsson, Nicholas M. Franko, Jenni Logue, Najeeha Talat Iqbal, Ignacio Mazzitelli, Jorge Geffner, Renata Grifantini, Helen Chu, Andrea Gori, Agostino Riva, Olivier Giannini, Alessandro Ceschi, Paolo Ferrari, Pietro E. Cippa, Alessandra Franzetti-Pellanda, Christian Garzoni, Peter J. Halfmann, Yoshihiro Kawaoka, Christy Hebner, Lisa A. Purcell, Luca Piccoli, Matteo Samuele Pizzuto, Alexandra C. Walls, Michael S. Diamond, Amalio Telenti, Herbert W. Virgin, Antonio Lanzavecchia, Gyorgy Snell, David Veesler, Davide Corti
Summary: The Omicron variant of SARS-CoV-2 has raised concerns due to its 37 amino acid substitutions in the spike protein, particularly in the receptor-binding domain (RBD), leading to increased binding affinity with human ACE2. Neutralizing activity against Omicron was greatly reduced in convalescent and vaccinated individuals compared to the ancestral virus, but this decrease was less significant after a third vaccine dose. Broadly neutralizing monoclonal antibodies recognizing conserved RBD epitopes may be crucial in combating the Omicron variant and future zoonotic transmissions.
Letter
Biochemistry & Molecular Biology
Michael Boeckh, Helen Y. Chu, Janet A. Englund, Christina M. Lockwood, Deborah A. Nickerson, Jay Shendure, Lea Starita
Review
Immunology
Jennifer K. Logue, Helen Y. Chu
Summary: This article discusses the importance of establishing a longitudinal observational cohort study during the COVID-19 pandemic and provides guidance for future pandemic preparedness.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Biochemical Research Methods
Tomer Zohar, Caroline Atyeo, Caitlin R. Wolf, Jennifer K. Logue, Kiel Shuey, Nicholas Franko, Robert Y. Choi, Anna Wald, David M. Koelle, Helen Y. Chu, Douglas A. Lauffenburger, Galit Alter
Summary: Monocytes are versatile innate immune cells that play a significant role in pathogen clearance, immune coordination, and induction of adaptive immunity. This study presents a multifaceted method for studying the interaction between antibodies and monocytes, aiming to understand the role of humoral immunity in driving monocyte functions in various diseases.
JOURNAL OF IMMUNOLOGICAL METHODS
(2022)
Article
Virology
Raaka Kumbhakar, Moni Neradilek, Ruanne Barnabas, Jenell Stewart, Helen C. Stankiewicz Karita, Raphael J. Landovitz, Patricia J. Kissinger, Keith R. Jerome, Michael K. Paasche-Orlow, Anna Bershteyn, Helen Y. Chu, Kathleen M. Neuzil, Alexander L. Greninger, Alfred Luk, Anna Wald, Elizabeth R. Brown, Christine Johnston
Summary: Two randomized controlled trials found no clinical benefit of hydroxychloroquine (HCQ) in postexposure prophylaxis or early treatment of SARS-CoV-2 infection. Analysis of data from these studies showed that HCQ did not affect viral clearance.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Multidisciplinary Sciences
John E. Bowen, Amin Addetia, Ha Dang, Cameron Stewart, Jack T. Brown, William K. Sharkey, Kaitlin R. Sprouse, Alexandra C. Walls, Ignacio G. Mazzitelli, Jennifer K. Logue, Nicholas M. Franko, Nadine Czudnochowski, Abigail E. Powell, Exequiel Jr Dellota Jr, Kumail Ahmed, Asefa Shariq Ansari, Elisabetta Cameroni, Andrea Gori, Alessandra Bandera, Christine M. Posavad, Jennifer M. Dan, Zeli Zhang, Daniela Weiskopf, Alessandro Sette, Shane Crotty, Najeeha Talat Iqbal, Davide Corti, Jorge Geffner, Gyorgy Snell, Renata Grifantini, Helen Y. Chu, David Veesler
Summary: The Omicron variant of concern, characterized by numerous spike mutations, exhibits enhanced binding to ACE2, reduced fusogenicity, and reduced neutralizing activity against plasma induced by infection or vaccines. However, booster doses based on the Wuhan-Hu-1 spike sequence significantly increase neutralizing antibody titers and breadth against multiple Omicron sublineages.
Article
Microbiology
Allison J. Greaney, Rachel T. Eguia, Tyler N. Starr, Khadija Khan, Nicholas Franko, Jennifer K. Logue, Sandra M. Lord, Cate Speake, Helen Y. Chu, Alex Sigal, Jesse D. Bloom
Summary: Exposure to SARS-CoV-2 variants and vaccinations affects the specificity of antibody responses. The Delta variant elicits a neutralizing antibody response focused on the receptor-binding domain, similar to early 2020 viruses but different from the Beta variant. Mutations to the class 1 epitope have a significant impact on antibody binding and neutralization in the Delta spike.
Review
Microbiology
Eric J. Chow, Timothy M. Uyeki, Helen Y. Chu
Summary: The COVID-19 pandemic has significantly affected global respiratory virus infections, with varying degrees of changes seen in different virus types. Non-pharmaceutical interventions have been implemented by governments, with differences observed after the availability of COVID-19 vaccines. Reductions in respiratory virus infections have resulted in decreased hospitalizations and deaths associated with these infections.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Hematology
Masumi Ueda Oshima, Hu Xie, Danniel Zamora, Mary E. Flowers, Geoffrey R. Hill, Marco B. Mielcarek, Brenda M. Sandmaier, Ted A. Gooley, Michael J. Boeckh
Summary: The kinetics of CMV reactivation after hematopoietic cell transplantation with different methods of GVHD prophylaxis were studied. CMV reactivation and disease were compared among 780 patients given HLA-matched PBSC grafts and treated with PTCy, MMF, or MTX. Hazards of CMV reactivation and viral load AUC were assessed. MMF was associated with a higher risk of early CMV reactivation and higher viral load AUC compared to PTCy and MTX.
Article
Multidisciplinary Sciences
Amin Addetia, Luca Piccoli, James Brett Case, Young-Jun Park, Martina Beltramello, Barbara Guarino, Ha Dang, Guilherme Dias de Melo, Dora Pinto, Kaitlin Sprouse, Suzanne M. Scheaffer, Jessica Bassi, Chiara Silacci-Fregni, Francesco Muoio, Marco Dini, Lucia Vincenzetti, Rima Acosta, Daisy Johnson, Sambhavi Subramanian, Christian Saliba, Martina Giurdanella, Gloria Lombardo, Giada Leoni, Katja Culap, Carley Mcalister, Anushka Rajesh, Exequiel Dellota, Jiayi Zhou, Nisar Farhat, Dana Bohan, Julia Noack, Alex Chen, Florian A. Lempp, Joel Quispe, Lauriane Kergoat, Florence Larrous, Elisabetta Cameroni, Bradley Whitener, Olivier Giannini, Pietro Cippa, Alessandro Ceschi, Paolo Ferrari, Alessandra Franzetti-Pellanda, Maira Biggiogero, Christian Garzoni, Stephanie Zappi, Luca Bernasconi, Min Jeong Kim, Laura E. Rosen, Gretja Schnell, Nadine Czudnochowski, Fabio Benigni, Nicholas Franko, Jennifer K. Logue, Courtney Yoshiyama, Cameron Stewart, Helen Chu, Herve Bourhy, Michael A. Schmid, Lisa A. Purcell, Gyorgy Snell, Antonio Lanzavecchia, Michael S. Diamond, Davide Corti, David Veesler
Summary: The recently emerged BQ.1.1 and XBB.1.5 variants of SARS-CoV-2 have a higher affinity for the host ACE2 receptor and more efficiently promote fusion with host cell membranes compared to earlier Omicron variants. Although the neutralizing activity is reduced, vaccine-induced human plasma antibodies still cross-react with and trigger effector functions against current Omicron variants, providing a mechanism of protection against disease.
Article
Infectious Diseases
Collrane Frivold, Denise J. Mcculloch, Seda Ekici, Emily T. Martin, Michael L. Jackson, Helen Y. Chu
Summary: Acute respiratory infections (ARIs) during pregnancy are associated with poor maternal and fetal outcomes. By testing for respiratory viruses among pregnant and non-pregnant individuals, we found differences in virus detection based on pregnancy status.
INFLUENZA AND OTHER RESPIRATORY VIRUSES
(2023)