Article
Microbiology
Jian Du, Jingtao Gao, Yanhong Yu, Qingfeng Li, Guanghong Bai, Wei Shu, Mengqiu Gao, Yuhong Liu, Lu Wang, Yufeng Wang, Zhongtan Xue, Fengmin Huo, Liang Li, Yu Pang
Summary: In this retrospective study in China, researchers aimed to determine the prevalence of linezolid resistance among MDR-TB patients, monitor changes in linezolid susceptibility during treatment, and explore molecular mechanisms of resistance. They found that 6.9% of patients had linezolid resistance, with a higher rate in those previously exposed to the drug. The most common genetic mutation conferring resistance was a Cys154Arg substitution in the ribosomal protein L3.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yuan Yuan, Jinmeng Li, Yanhong Chen, Qingshan Cai, Yingying Xu, Luting Lin, Yazhen Lang, Suhang Guo, Ruoying Zhang, Xinjun Cai
Summary: This study investigates the mechanism of linezolid-induced peripheral neuropathy in multidrug-resistant tuberculosis (MDR-TB). The results show that linezolid inhibits autophagy flux, leading to the development of peripheral neuropathy. The findings suggest a potential neuroprotective role of autophagy in preventing linezolid-induced neuropathy in MDR-TB patients.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Haoyue Zhang, Yuying He, Lina Davies Forsman, Jakob Paues, Jim Werngren, Katarina Niward, Thomas Schon, Judith Bruchfeld, Jan-Willem Alffenaar, Yi Hu
Summary: A population pharmacokinetic (PK) model for linezolid was developed, and a PK/pharmacodynamics (PD) threshold for successful treatment outcome was identified. The currently recommended linezolid doses were evaluated, and it was found that an AUC(0-24h)/MIC > 125 was associated with successful treatment outcomes.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Immunology
Tasnim Hasan, Ellie Medcalf, Bern-Thomas Nyang'wa, Erica Egizi, Catherine Berry, Matthew Dodd, Salah Foraida, Medea Gegia, Mengchun Li, Fuad Mirzayev, Hannah Morgan, Ilaria Motta, Linh Nguyen, Samuel Schumacher, Tim Schlub, Greg Fox
Summary: By reviewing and meta-analyzing clinical trial data, it was found that BPaL-containing regimens with a daily dose of 600 mg linezolid showed good tolerability, which may improve the tolerability of treatment for MDR/RR-TB.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Anastasia Ushtanit, Yulia Mikhailova, Alexandra Lyubimova, Marina Makarova, Svetlana Safonova, Alexey Filippov, Sergey Borisov, Danila Zimenkov
Summary: Linezolid resistance mainly emerged during treatment with the latest regimen, and three primary cases with linezolid resistance questioned the possible transmission of totally drug-resistant tuberculosis in the Moscow region, which requires further investigation.
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
Anjeli Mase, Phil Lowenthal, Lisa True, Leslie Henry, Pennan Barry, Jennifer Flood
Summary: In MDR TB patients in California, switching to a low dose of linezolid resulted in longer tolerability, better treatment outcomes, and fewer adverse events.
OPEN FORUM INFECTIOUS DISEASES
(2022)
Article
Immunology
Johannes Eimer, Mathilde Frechet-Jachym, Damien Le Du, Eric Caumes, Najoua El-Helali, Dhiba Marigot-Outtandy, Frederic Mechai, Gilles Peytavin, Valerie Pourcher, Christophe Rioux, Yazdan Yazdanpanah, Jerome Robert, Lorenzo Guglielmetti
Summary: This study evaluated the association between linezolid trough concentrations and severe toxicity in patients treated for multidrug-resistant tuberculosis. The results showed that linezolid concentrations >2 mg/L were strongly associated with the development of severe treatment-emergent toxicity, suggesting the need for an individual risk-benefit assessment in patients with high trough concentrations.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Jie Qiao, Lin Yang, Jing Feng, Xiyong Dai, Feng Xu, Ping Xia
Summary: The study aimed to explore the efficacy and safety of linezolid-based chemotherapeutic regimens for patients with postoperative multidrug-resistant spinal tuberculosis. The results showed that linezolid-based chemotherapy can effectively treat patients with postoperative multidrug-resistant spinal tuberculosis with higher effective rates and lower pain severity, but also with higher rates of adverse reactions.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Chun-Hua Li, Xiao Fan, Sheng-Xiu Lv, Xue-Yan Liu, Jia-Nan Wang, Yong-Mei Li, Qi Li
Summary: The value of integrating clinical and computed tomography (CT) features to predict multidrug-resistant tuberculosis (MDR-PTB) was explored. Male sex, retreated history, longer duration of previous anti-TB treatment, lower CD4+ T lymphocyte count, thick-walled cavity, centrilobular micronodules and tree-in-bud sign, bronchial stenosis, pleural and pericardial thickening were identified as the most effective variations associated with MDR-PTB. The combined model achieved an accuracy of 78.6% and an external validation cohort obtained an accuracy of 81.7%.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Infectious Diseases
Ying Zhang, Ruiqiu Zhao, Zhenzhen Zhang, Quanbo Liu, Aihua Zhang, Qiaoli Ren, Siyuan Li, Xiaoru Long, Hongmei Xu
Summary: The study analyzed influencing factors of pediatric multidrug-resistant tuberculosis (MDR-TB) and the validation of whole-genome sequencing (WGS) in drug-resistant TB. It found that the BCG vaccine is a protective factor for MDR-TB, which may lead to more severe cases and lower recovery rates compared to drug-susceptible TB. WGS can accurately predict drug susceptibility test results for anti-TB drugs in children, aiding in diagnosis and precise treatment.
INFECTION AND DRUG RESISTANCE
(2021)
Article
Infectious Diseases
Hannah Yejin Kim, Evelien Ruiter, Erwin M. Jongedijk, Hemanth Kumar Ak, Ben J. Marais, P. K. Bhavani, Shailendra Sawleshwarkar, Daan J. Touw, Jan-Willem Alffenaar
Summary: The study validated the feasibility and accuracy of a UV spectrophotometric assay using non-invasive saliva sampling for linezolid.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Immunology
Russell R. Kempker, Alison G. C. Smith, Teona Avaliani, Mariam Gujabidze, Tinatin Bakuradze, Shorena Sabanadze, Zaza Avaliani, Jeffrey M. Collins, Henry M. Blumberg, Mohammad H. Alshaer, Charles A. Peloquin, Maia Kipiani
Summary: This study fills a critical knowledge gap regarding the ability of antituberculosis drugs to penetrate into the cerebrospinal fluid (CSF) and provides valuable pharmacokinetic data for the treatment of tuberculosis meningitis (TBM). Linezolid and cycloserine showed moderate to high CSF penetration and may be effective drugs for TBM treatment, while the efficacy of bedaquiline, delamanid, and clofazimine remains uncertain due to their low CSF penetration.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Scott K. Heysell, Stellah G. Mpagama, Oleg B. Ogarkov, Mark Conaway, Shahriar Ahmed, Svetlana Zhdanova, Suporn Pholwat, Mohammad H. Alshaer, Anna M. Chongolo, Buliga Mujaga, Margaretha Sariko, Sabrina Saba, S. M. Mazidur Rahman, Mohammad Khaja Mafij Uddin, Alexey Suzdalnitsky, Elena Moiseeva, Elena Zorkaltseva, Mikhail Koshcheyev, Serhiy Vitko, Blandina T. Mmbaga, Gibson S. Kibiki, Jotam G. Pasipanodya, Charles A. Peloquin, Sayera Banu, Eric R. Houpt
Summary: In a multicountry, prospective cohort, serum pharmacokinetics and Mycobacterium tuberculosis minimum inhibitory concentrations were variable, yet certain drugs' parameters were predictive of clinical outcome for rifampin-resistant/multidrug-resistant tuberculosis.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Li Wang, Ruoyan Ying, Yidian Liu, Qin Sun, Wei Sha
Summary: This study aimed to investigate the metabolic changes in drug-susceptible and multidrug-resistant Mycobacterium tuberculosis and provide insights into the mechanisms of drug resistance based on metabolic pathways.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Hematology
Anne-Grete Martson, Ana Rita da Silva Ferreira, Anette Veringa, Lei Liu, Hannah R. Wardill, Lenneke A. T. Junier, Tjip S. van der Werf, Hermie J. M. Harmsen, Marieke G. G. Sturkenboom, Lambert F. Span, Wim J. E. Tissing, Jan-Willem C. Alffenaar
Summary: This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. It was found that severe gastrointestinal mucositis could compromise drug absorption and a weak correlation between ciprofloxacin and citrulline concentrations was observed. Further research is needed to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.
ANNALS OF HEMATOLOGY
(2023)
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
Medical Laboratory Technology
Sjanene Marfil, Anne-Grete Maertson, Marlous Toren-Wielema, Coretta Leer-Buter, Elisabeth. H. Scholvinck, Jan-Willem C. Alffenaar, Daan. J. Touw, Marieke G. G. Sturkenboom
Summary: Ganciclovir therapeutic drug monitoring (TDM) in 12 treatment episodes showed significant variability in both trough concentration and area under the 24-hour concentration-time curve (AUC24), both within and between individuals. Subtherapeutic concentrations were found in 30% of the treatment episodes, despite adequate valganciclovir dosing. However, a decrease in viral load was still observed. These findings highlight the importance of evaluating target concentrations and assessing the applicability of ganciclovir TDM in children.
THERAPEUTIC DRUG MONITORING
(2023)
Article
Pharmacology & Pharmacy
Haoyue Zhang, Yuying He, Lina Davies Forsman, Jakob Paues, Jim Werngren, Katarina Niward, Thomas Schon, Judith Bruchfeld, Jan-Willem Alffenaar, Yi Hu
Summary: A population pharmacokinetic (PK) model for linezolid was developed, and a PK/pharmacodynamics (PD) threshold for successful treatment outcome was identified. The currently recommended linezolid doses were evaluated, and it was found that an AUC(0-24h)/MIC > 125 was associated with successful treatment outcomes.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Elise A. Schubert, Johannes C. Alffenaar, Masego T. Johnstone, John W. Barlow, Nial J. Wheate
Summary: This study found that certain concomitant medications and cannabis constituents may be associated with the incidence of adverse events when initiating medicinal cannabis.
INTERNATIONAL JOURNAL OF PHARMACY PRACTICE
(2023)
Article
Clinical Neurology
Elise A. Schubert, Masego T. Johnstone, Melissa J. Benson, Johannes C. Alffenaar, Nial J. Wheate
Summary: This study examined the tolerability and effectiveness of medicinal cannabis in patients with chronic, refractory pain, with a subset analysis on arthritis. The results showed that balanced CBD:THC products significantly reduced pain intensity scores, with 22% of patients experiencing a clinically meaningful reduction. Additionally, patients using CBD:THC balanced products showed improvements in various health-related quality of life outcomes.
BRITISH JOURNAL OF PAIN
(2023)
Article
Microbiology
Yue Zhu, Limei Zhu, Lina Davies Forsman, Jakob Paues, Jim Werngren, Katarina Niward, Thomas Schon, Judith Bruchfeld, Haiyan Xiong, Jan-Willem Alffenaar, Yi Hu
Summary: This study aimed to estimate the population PK parameters for cycloserine, identify clinically relevant PK/PD thresholds, and evaluate the current recommended dosage. Data showed that with WHO-recommended doses, the probability of target attainment exceeded 90%.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Prakruti S. Rao, Nisha Modi, Nam-Tien Tran Nguyen, Dinh Hoa Vu, Yingda L. Xie, Monica Gandhi, Roy Gerona, John Metcalfe, Scott K. Heysell, Jan-Willem C. Alffenaar
Summary: Quantifying drug exposure is crucial for personalized dose adjustment in tuberculosis patients. Traditional methods using serum or plasma samples for drug monitoring have logistical challenges. Less invasive and lower cost tests using alternative biomatrices can improve feasibility.
CLINICAL PHARMACOKINETICS
(2023)
Article
Infectious Diseases
D. Abraham Van den Born, Anne-Grete Martson, Anette Veringa, Nieko C. Punt, Tjip S. Van der Werf, Jan-Willem C. Alffenaar, Marieke G. G. Sturkenboom, Daan J. Touw
Summary: This study investigated the effect of inflammation on the metabolism of voriconazole and found that C-reactive protein (CRP) was the only significant covariate. The final pharmacokinetic model, which included CRP as a covariate, can be applied in clinical care.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
Cindy Lau, Deborah Marriott, Jessica Bui, Melanie Figtree, Michael Gould, Adriana Chubaty, Yuen Su, Suman Adhikari, Pam Konecny, Kristi Kozierowski, Taylor Holland, Eliza Milliken, Ayesha Akram, Alexander Mcnamara, Yihui Sun, Sebastiaan Van Hal, Asad E. Patanwala, Aryan Shahabi-Sirjani, Timothy Gray, Chin Yen Yeo, Angela Netluch, Stephanie Halena, Marcelle Appay, Rozanna Alameddine, Fiona Yin, Quoc Nguyen, Mei-Yi So, Indy Sandaradura, Hannah Yejin Kim, Semun Galimam, Nicole Cerruto, Tony Lai, Timothy Gilbey, Kathryn Daveson, Stephanie E. Reuter, Jonathan Penm, Jan-Willem Alffenaar
Summary: This study aimed to evaluate linezolid toxicity in a large multicentre cohort and found that linezolid treatment-limiting toxicity remains a problem. TDM-guided dose optimisation significantly reduced the risk of toxicity and a treatment duration beyond 28 days was no longer significantly associated with toxicity.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Public, Environmental & Occupational Health
Afifah Machlaurin, Jos Luttjeboer, Didik Setiawan, Tjipke Sytse van der Werf, Maarten J. Postma
Summary: Combining home visit vaccination and a less restrictive open vial strategy for timely BCG vaccination can significantly reduce childhood TB cases and TB-related mortality in high-incidence outreach settings. Although outreach activities are more expensive than vaccination at a health care facility only, these activities proved to be cost-effective. These strategies might also be beneficial in other high-incidence outreach settings.
JOURNAL OF GLOBAL HEALTH
(2023)
Article
Pharmacology & Pharmacy
Samiksha Ghimire, Gladys Molinas, Arturo Battaglia, Nilza Martinez, Luis Gomez Paciello, Sarita Aguirre, Jan-Willem C. Alffenaar, Marieke G. G. Sturkenboom, Cecile Magis-Escurra
Summary: The study aimed to evaluate the difference in drug exposure of rifampicin in native versus non-native Paraguayan populations using dried blood spot samples collected utilizing a limited sampling strategy. The results showed that native patients had comparable drug exposure to non-native patients, with only a small percentage of patients having a rifampicin exposure above the threshold. This study successfully used DBS and limited sampling for the estimation of rifampicin exposure.
Review
Infectious Diseases
Ricky Hao Chen, Toni Michael, Johanna Kuhlin, Thomas Schon, Sophie Stocker, Jan-Willem C. Alffenaar
Summary: This systematic review aims to evaluate the concentration-effect relationship of Pyrazinamide (PZA) in tuberculosis treatment. The study found that there is a positive correlation between PZA dose and antibacterial effect. Further dose optimization studies are justified.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
O. W. Akkerman, R. D. C. Dijkwel, H. A. M. Kerstjens, T. S. van der Werf, S. Srivastava, M. G. G. Sturkenboom, M. S. Bolhuis
Summary: This study describes the pharmacokinetics of rifampicin (RIF) and isoniazid (INH) in patients with drug-susceptible tuberculosis in a real-world setting. The results show that more than 50% of patients had drug exposure below the pre-specified target values, highlighting the need for better justification of drug exposure targets.
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
(2023)
Article
Infectious Diseases
Sanjay Singh, Tawanda Gumbo, Jan-Willem Alffenaar, Gunavanthi D. Boorgula, Prem Shankar, Tania A. Thomas, Keertan Dheda, Lesibana Malinga, Prithvi Raj, Santosh Aryal, Shashikant Srivastava
Summary: By testing and studying, it was found that the combination of meropenem with beta-lactamase inhibitors (BLIs) could potentially be an effective treatment regimen for multidrug-resistant tuberculosis (MDR-TB). The meropenem-vaborbactam-moxifloxacin backbone regimen has implications for creating a new effective MDR-TB regimen.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
