Article
Pharmacology & Pharmacy
Yangming Ding, Haiting Liu, Furun Wang, Lei Fu, Hui Zhu, Shuang Fu, Ning Wang, Xiaomei Zhuang, Yu Lu
Summary: The combination of BDQ and TBI-166 significantly reduces exposure to toxic metabolite M2 by inhibiting the activity of the CYP3A4 pathway.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Microbiology
Simon E. Koele, Stijn W. van Beek, Gary Maartens, James C. M. Brust, Elin M. Svensson
Summary: Interruption of treatment is common in drug-resistant tuberculosis patients. Restarting treatment with bedaquiline without a loading dose after an interruption could increase the risk of suboptimal treatment outcome and resistance development. This study identified suitable loading dose strategies for bedaquiline restart based on simulation and recommended reloading periods of 3 days, 1 week, and 2 weeks for interruptions of different durations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Editorial Material
Immunology
Takashi Yoshiyama, Akiko Takaki, Akio Aono, Satoshi Mitarai, Masao Okumura, Ken Ohta, Seiya Kato
Summary: This study reported a clinical case of simultaneous acquisition of resistance to bedaquiline and delamanid in Mycobacterium tuberculosis, with specific nucleotide insertions identified through whole genome sequencing. The minimum inhibitory concentrations for bedaquiline and delamanid were determined to be 0.25 μg/mL and >2.0 μg/mL, respectively.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Sheng-Han Wu, Hsin-Hua Chan, Hseuh-Chien Hsiao, Ruwen Jou
Summary: This study found that redefining the intermediate susceptibility category for BDQ resistance and conducting genotypic analyses for MGIT-BDQ borderline resistance isolates are recommended to better manage drug-resistant tuberculosis cases. Additionally, the study observed that Rv0678 mutations were not a robust marker of BDQ resistance and were not associated with treatment outcomes in BDQ-resistant patients without exposure.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Jin Zou, Shuyan Chen, Weiqiao Rao, Liang Fu, Jiancong Zhang, Yunli Liao, Ying Zhang, Ning Lv, Guofang Deng, Shijin Yang, Liang Lin, Lujin Li, Siqi Liu, Jiuxin Qu
Summary: This study developed a population pharmacokinetic model of bedaquiline and investigated its concentration-time data in Chinese adult patients with MDR-TB. The study found that the clearance of bedaquiline was significantly associated with genetic polymorphism and liver function, highlighting the importance of considering these factors in dosing bedaquiline for MDR-TB patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Immunology
Tyler S. Brown, Linrui Tang, Shaheed Vally Omar, Lavania Joseph, Graeme Meintjes, Gary Maartens, Sean Wasserman, N. Sarita Shah, Maha R. Farhat, Neel R. Gandhi, Nazir Ismail, James C. M. Brust, Barun Mathema
Summary: Characterizing serial Mycobacterium tuberculosis (Mtb) isolates collected during bedaquiline (BDQ)-based treatment provides insights into the etiologies of BDQ resistance. The study found that BDQ-resistant TB can arise through multiple processes, including transmission of strains with pre-existing resistance. Capturing the within-host diversity of these infections could potentially improve clinical diagnosis, population-level surveillance, and molecular diagnostic test development.
CLINICAL INFECTIOUS DISEASES
(2023)
Review
Microbiology
Francesco Pecora, Giulia Dal Canto, Piero Veronese, Susanna Esposito
Summary: This article discusses the current knowledge of managing MDR-TB and XDR-TB in children, focusing on two promising new drugs: bedaquiline and delamanid. While data on these new anti-TB drugs in pediatric populations are limited, they appear to have good tolerability and efficacy in children with MDR-TB/XDR-TB. More evidence is needed to guide their use in designing effective shorter regimens and reducing adverse effects, drug interactions, and therapeutic failure.
Article
Immunology
Chandrasekaran Padmapriyadarsini, Vikram Vohra, Anuj Bhatnagar, Rajesh Solanki, Rathinam Sridhar, Lalitkumar Anande, M. Muthuvijaylakshmi, Miraa Bhatia, Bharathi Jeyadeepa, Gaurav Taneja, S. Balaji, Prashant Shah, N. Saravanan, Vijay Chauhan, Hemanth Kumar, Chinnayin Ponnuraja, Viktoriya Livchits, Monica Bahl, Umesh Alavadi, K. S. Sachdeva, Soumya Swaminathan
Summary: This study demonstrates that highly drug-resistant pulmonary tuberculosis can be effectively treated with an entirely oral, short-course regimen of bedaquiline, delamanid, linezolid, and clofazimine. Toxicities can be identified early and corrected, reducing the burden on patients and the treatment program.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Microbiology
Kone Kaniga, Rumina Hasan, Ruwen Jou, Edita Vasiliauskiene, Charoen Chuchottaworn, Nazir Ismail, Beverly Metchock, Skaidrius Miliauskas, Nguyen Viet Nhung, Camilla Rodrigues, Soyoun Shin, Hulya Simsek, Saijai Smithtikarn, Anh Le Thi Ngoc, Jirakan Boonyasopun, Mubin Kazi, Seungmo Kim, Phalin Kamolwat, Greta Musteikiene, Catherine Ann Sacopon, Sabira Tahseen, Laima Vasiliauskaite, Mei-Hua Wu, Shaheed Vally Omar
Summary: Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) conducted a 5-year surveillance study across 11 countries, finding low resistance rates to Bedaquiline and no treatment-limiting patterns of cross-resistance or coresistance with key TB drugs.
JOURNAL OF CLINICAL MICROBIOLOGY
(2022)
Review
Infectious Diseases
Anna Starshinova, Irina Dovgalyk, Ekaterina Belyaeva, Anzhela Glushkova, Nikolay Osipov, Dmitry Kudlay
Summary: The use of bedaquiline in the treatment of multidrug- and extensive drug-resistant tuberculosis is of great relevance. The study showed that bedaquiline treatment achieved high conversion and recovery rates, with low rates of treatment interruption.
Review
Pharmacology & Pharmacy
Kyle J. Wilby
Summary: Tuberculosis remains a major infectious disease burden globally. Bedaquiline, an orally administered drug, is effective in treating multi-drug-resistant tuberculosis. This review examines the pharmacokinetics of bedaquiline and highlights the need for further research on exposure-response relationships, optimal dosing, and guidance for co-administration with other drugs.
CLINICAL PHARMACOKINETICS
(2022)
Review
Immunology
Hanzhao Zhu, Xintong Zhou, Zengfang Zhuang, Lianju Li, Jing Bi, Kaixia Mi
Summary: Tuberculosis (TB) remains a significant public health issue, especially among children who often receive insufficient diagnosis and treatment. The emergence of drug-resistant strains has further complicated the situation, with limited effectiveness of current treatments. New drugs like bedaquiline and delamanid show promise in treating drug-resistant TB, but the lack of clinical data in children hinders the development of child-friendly formulations. This paper provides a comprehensive review of the development, mechanisms, efficacy, safety considerations, and current use of these drugs in treating drug-resistant TB in children.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Letter
Immunology
James Millard, Stephanie Rimmer, Camus Nimmo, Max O'Donnell
Summary: New classes of antitubercular drugs, diarylquinolines and nitroimidazoles, have been effective in treating drug-resistant tuberculosis. However, a case of bedaquiline and delamanid resistance in a patient with extensively drug-resistant tuberculosis and HIV has been reported in South Africa.
EMERGING INFECTIOUS DISEASES
(2023)
Article
Immunology
Hyeontaek Hwang, Hyungseok Kang, Yong-Soo Kwon, Doosoo Jeon, Tae Sun Shim, Jae-Joon Yim
Summary: A nationwide cohort study in South Korea assessed and compared the final treatment outcomes of patients with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline or delamanid. The study found that the initial choice of bedaquiline or delamanid did not significantly impact the final treatment outcome or the frequencies of adverse events among patients.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
James C. M. Brust, Neel R. Gandhi, Sean Wasserman, Gary Maartens, Shaheed Omar, Nazir A. Ismail, Angela Campbell, Lindsay Joseph, Alexandria Hahn, Salim Allana, Alfonso C. Hernandez-Romieu, Chenshu Zhang, Koleka Mlisana, Charle A. Viljoen, Benjamin Zalta, Ismaeel Ebrahim, Meghan Franczek, Iqbal Master, Limpho Ramangoaela, Julian Te Riele, Graeme Meintjes
Summary: This study looked at patients with rifampin-resistant tuberculosis in three provinces of South Africa who were treated with bedaquiline and found that severe QT prolongation was uncommon and did not usually require permanent discontinuation of the medication. Older age was associated with a higher risk of QT prolongation, but it was not more common or severe in participants receiving concurrent lopinavir-ritonavir. Close monitoring of the QT interval may be advisable in older patients.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Sara N. Salerno, Edmund Capparelli, Helen McIlleron, Jacqueline G. Gerhart, Julie B. Dumond, Angela D. M. Kashuba, Paolo Denti, Daniel Gonzalez
Summary: This study used physiologically based pharmacokinetic modeling to optimize the dosage of LPV/RTV in children with HIV/TB co-infection, achieving therapeutic levels of LPV trough concentrations.
Article
Pharmacology & Pharmacy
Muhammed Shiraz Moosa, Giusy Russomanno, Jeffrey R. Dorfman, Hannah Gunter, Chandni Patel, Eithne Costello, Dan Carr, Gary Maartens, Munir Pirmohamed, Christopher Goldring, Karen Cohen
Summary: This study investigated the concentrations of miR-122 in participants with antituberculosis drug-induced liver injury (AT-DILI) and its correlation with alanine aminotransferase (ALT) concentrations. The study found that miR-122 concentrations in AT-DILI patients were significantly higher than those in healthy volunteers and in patients on antituberculosis therapy without liver injury, and N-acetylcysteine (NAC) had no effect on miR-122 concentrations.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yuanxi Zou, Veronique de Jager, Anneke C. Hesseling, Andreas H. Diacon, Lubbe Wiesner, Joni Mostert, Elin M. Svensson, Anthony Garcia-Prats
Summary: The study evaluated the bioavailability and acceptability of dispersed 50-mg delamanid tablets. The results showed that the dispersed tablets had a bioavailability of 107%, meeting the criteria for bioequivalence. Additionally, the majority of participants found the dispersed formulation acceptable in terms of palatability. Therefore, this can be a suitable option for patients who cannot swallow whole tablets, especially children.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Immunology
Ying Zhao, Rulan Griesel, Zaayid Omar, Bryony Simmons, Andrew Hill, Gert van Zyl, Claire Keene, Gary Maartens, Graeme Meintjes
Summary: This study evaluated the need for an initial dolutegravir dose adjustment in adults switching from first-line TEE treatment to TLD. The results showed that in patients with unsuppressed HIV-1 RNA levels and substantial baseline resistance to nucleoside reverse transcriptase inhibitors, a high proportion achieved virologic suppression without the need for an initial dolutegravir dose adjustment.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Angharad G. Davis, Sean Wasserman, Cari Stek, Mpumi Maxebengula, C. Jason Liang, Stephani Stegmann, Sonya Koekemoer, Amanda Jackson, Yakub Kadernani, Marise Bremer, Remy Daroowala, Saalikha Aziz, Rene Goliath, Louise Lai Sai, Thandi Sihoyiya, Paolo Denti, Rachel P. J. Lai, Thomas Crede, Jonathan Naude, Patryk Szymanski, Yakoob Vallie, Ismail Abbas Banderker, Muhammed S. Moosa, Peter Raubenheimer, Sally Candy, Curtis Offiah, Gerda Wahl, Isak Vorster, Gary Maartens, John Black, Graeme Meintjes, Robert J. Wilkinson
Summary: In this study, it was demonstrated that high-dose rifampicin and adjunctive linezolid is safe in adult HIV-associated tuberculous meningitis patients. Larger studies are needed to evaluate the potential toxicity of high-dose aspirin and its benefits on morbidity and mortality.
CLINICAL INFECTIOUS DISEASES
(2023)
Review
Respiratory System
Jessica M. Aguilar Diaz, Ahmed A. Abulfathi, Lindsey H. M. te Brake, Jakko van Ingen, Saskia Kuipers, Cecile Magis-Escurra, Jelmer Raaijmakers, Elin M. Svensson, Martin J. Boeree
Summary: While tuberculosis is preventable and curable, the treatment is complex due to factors such as lengthy duration, poor patient adherence, drug resistance, and comorbidities. Therefore, there is a need for the development of new drugs and/or regimens. This review highlights various drug candidates that could be part of future tuberculosis therapies.
Correction
Microbiology
Louvina E. van der Laan, Anthony J. Garcia-Prats, H. Simon Schaaf, Maxwell Chirehwa, Jana L. Winckler, Jun Mao, Heather R. Draper, Lubbe Wiesner, Jennifer Norman, Helen McIlleron, Peter R. Donald, Anneke C. Hesseling, Paolo Denti
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
M. T. Chirehwa, J. E. Resendiz-Galvan, R. Court, M. De Kock, L. Wiesner, N. de Vries, J. Harding, T. Gumbo, R. Warren, G. Maartens, P. Denti, H. McIlleron
Summary: In order to optimize dosing, the researchers investigated the pharmacokinetics and minimum inhibitory concentration (MIC) distribution of moxifloxacin in participants with multidrug-resistant tuberculosis (MDR-TB). Using nonlinear mixed-effects modeling and simulations, they analyzed plasma drug concentrations and clinical data to evaluate different dosing scenarios. The results showed that participants treated with efavirenz had increased clearance of moxifloxacin, resulting in reduced exposure. Simulations suggested that higher doses of moxifloxacin were needed to achieve target levels, particularly in heavier participants. The high-dose WHO regimen yielded more balanced exposures across different weight ranges. The safety of higher doses of moxifloxacin should be confirmed in clinical settings.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Noha Abdelgawad, Mvuwo (Phophi) Tshavhungwe, Ursula Rohlwink, Helen McIlleron, Mahmoud T. Abdelwahab, Lubbe Wiesner, Sandra Castel, Chanel Steele, Johannes (Nico) Enslin, Nqobile Sindiswa Thango, Paolo Denti, Anthony Figaji
Summary: This analysis provides insights into the pharmacokinetics of rifampicin in children with tuberculous meningitis (TBM) and its penetration into brain tissue. The study characterizes the distribution of rifampicin in cerebrospinal fluid, lumbar and ventricular fluid, and brain extracellular fluid. It confirms rifampicin's ability to reach the brain tissue and provides valuable information for further research and treatment of TBM.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Immunology
Hylke Waalewijn, Alexander J. Szubert, Roeland E. Wasmann, Lubbe Wiesner, Chishala Chabala, Mutsa Bwakura-Dangarembizi, Shafic Makumbi, Joan Nangiya, Vivian Mumbiro, Veronica Mulenga, Victor Musiime, Lara N. Monkiewicz, Anna L. Griffiths, Alasdair Bamford, Katja Doerholt, Paolo Denti, David M. Burger, Diana M. Gibb, Helen M. McIlleron, Angela Colbers
Summary: In a pharmacokinetic substudy of the CHAPAS-4 trial in African children, it was found that the combination of TAF and tenofovir, when dosed according to WHO-recommended weight bands and combined with dolutegravir or ritonavir-boosted protease inhibitors, provided adequate exposure and efficacy.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Budi O. Susanto, Elin M. Svensson, Lindsey te Brake, Rob E. Aarnoutse, Martin J. Boeree, Ulrika S. H. Simonsson
Summary: This study suggests that a staggered dosing strategy of rifampicin can reduce side effects while maintaining better efficacy. Specifically, starting treatment with a low dose (20 mg/kg) for 7 days followed by a higher dose (40 mg/kg) predicted lower initial drug exposure and better bacterial killing rate.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Biotechnology & Applied Microbiology
Somila Mateza, Yuki Bradford, Gary Maartens, Simiso Sokhela, Nomathemba C. Chandiwana, Willem D. F. Venter, Frank A. Post, Marylyn D. Ritchie, David W. Haas, Phumla Sinxadi
Summary: Polymorphisms in the ABCC4 gene were found to be associated with changes in estimated glomerular filtration rate (eGFR) and urine beta 2-microglobulin/creatinine levels among HIV-positive individuals in South Africa. A polymorphism in the COL27A1 gene was also significantly associated with changes in eGFR.
PHARMACOGENETICS AND GENOMICS
(2023)
Article
Infectious Diseases
Michael J. Boyd, Marc Mendelson, Sipho K. Dlamini, Sean Wasserman, Ghaalied Fakier, Riyaadh Roberts, Nectarios S. Papavarnavas
Summary: This article reports a case of an unusual manifestation of schistosomiasis, in which mediastinal lymphoma was also discovered.
SOUTHERN AFRICAN JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Medical Laboratory Technology
Andre Joubert, Anton Joubert, Marthinus van der Merwe, Jennifer Norman, Sandra Castel, Paolo Denti, Karen Sliwa, Gary Maartens, Phumla Sinxadi, Lubbe Wiesner
Summary: This study validated an LC-MS/MS method for quantifying carvedilol, enalaprilat, and perindoprilat in DBS, and evaluated its feasibility as an adherence determining assay. The method was further clinically validated through a pharmacokinetic pilot study, showing that DBS and plasma concentrations can be used interchangeably. The results suggest that the assay is suitable for assessing adherence to carvedilol and perindoprilat, as well as enalaprilat.
JOURNAL OF MASS SPECTROMETRY AND ADVANCES IN THE CLINICAL LAB
(2023)
Article
Multidisciplinary Sciences
Marian Mazanhanga, Anton Joubert, Sandra Castel, Marthinus Van de Merwe, Gary Maartens, Sean Wasserman, Lubbe Wiesner
Summary: A simple and quick method was developed to analyze linezolid in cerebrospinal fluid of patients with tuberculous meningitis, and its accuracy and precision were validated. The concentration of linezolid in cerebrospinal fluid varied in patients and was not significantly affected by the filtration process.