Article
Microbiology
E. D. Pieterman, S. van den Berg, A. van der Meijden, E. M. Svensson, H. Bax, J. E. M. de Steenwinkel
Summary: Increasing the dosage of rifampin and rifapentine in HFIM did not always lead to improved antimycobacterial activity, and drug resistance was found to be unrelated to drug exposure for both drugs. Further parameters and readouts may be needed for proper assessment of the translational value of HFIM in preclinical models.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Immunology
Jonathon R. Campbell, Placide Nsengiyumva, Leslie Y. Chiang, Frances Jamieson, Hadeel Khadawardi, Henry K. -H. Mah, Olivia Oxlade, Hayden Rasberry, Elizabeth Rea, Kamila Romanowski, Natasha F. Sabur, Beate Sander, Aashna Uppal, James C. Johnston, Kevin Schwartzman, Sarah K. Brode
Summary: By estimating the costs of managing different forms of tuberculosis in Canada, it was found that the costs for TB infection were lower compared to drug-susceptible TB, while the costs for isoniazid-resistant TB were higher and those for MDR TB were the highest. Expanding the treatment for TB infection can reduce the high costs associated with managing TB disease.
EMERGING INFECTIOUS DISEASES
(2022)
Article
Pharmacology & Pharmacy
Gunavanthi D. Boorgula, Laxmi U. M. R. Jakkula, Tawanda Gumbo, Bockgie Jung, Shashikant Srivastava
Summary: The study compared microbial kill and resistance emergence of different rifamycins in the treatment of pulmonary MAC infection. Results showed no significant difference in efficacy and resistance suppression among the three rifamycins tested, and monotherapy with rifamycins was ineffective and led to drug resistance development.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Respiratory System
Lindsey H. M. te Brake, Veronique de Jager, Kim Narunsky, Naadira Vanker, Elin M. Svensson, Patrick P. J. Phillips, Stephen H. Gillespie, Norbert Heinrich, Michael Hoelscher, Rodney Dawson, Andreas H. Diacon, Rob E. Aamoutse, Martin J. Boeree
Summary: The study evaluated the safety, tolerability, pharmacokinetics, and early bactericidal activity of increasing doses of rifampicin in treatment-naive adult smear-positive patients with tuberculosis. While the 50mg/kg dose showed an increased bactericidal effect, it was not well tolerated, leading to treatment discontinuations, whereas the 40mg/kg dose was well tolerated and selected for further evaluation.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Immunology
Michelle K. Haas, Kaylynn Aiona, Kristine M. Erlandson, Robert W. Belknap
Summary: A retrospective cohort study in a US-based TB clinic comparing treatment completion and adverse events between patients initiating latent tuberculosis (LTBI) treatment with self-administered once-weekly isoniazid-rifapentine (3HP-SAT) and daily rifampin for 4 months (4R) found that 3HP-SAT was associated with higher treatment completion rates and lower rates of adverse events, particularly in individuals aged 50 and older. The study suggests that expanding the use of 3HP-SAT may enhance tuberculosis prevention strategies in the US.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Elisa H. Ignatius, Mahmoud Tareq Abdelwahab, Bronwyn Hendricks, Nikhil Gupte, Kim Narunsky, Lubbe Wiesner, Grace Barnes, Rodney Dawson, Kelly E. Dooley, Paolo Denti
Summary: Shorter, more potent regimens are needed for tuberculosis, and pretomanid offers potential as a treatment-shortening agent. However, it remains unclear how pretomanid interacts with key first-line drugs like rifampin and whether concurrent use may impact its efficacy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Medicine, General & Internal
Nicholas I. Paton, Christopher Cousins, Celina Suresh, Erlina Burhan, Ka Lip Chew, Victoria B. Dalay, Qingshu Lu, Tutik Kusmiati, Vincent M. Balanag, Shu Ling Lee, Rovina Ruslami, Yogesh Pokharkar, Irawaty Djaharuddin, Jani J. R. Sugiri, Rholine S. Veto, Christine Sekaggya-Wiltshire, Anchalee Avihingsanon, Rohit Sarin, Padmasayee Papineni, Andrew J. Nunn, Angela M. Crook, TRUNCATE-TB Trial Team
Summary: In this study, the effectiveness of two different treatment strategies for tuberculosis was evaluated. The results showed that initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment, with a shorter duration of treatment and no evident safety concerns.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Multidisciplinary Sciences
Miguel Santin, Sandra Perez-Recio, Maria D. Grijota, Luis Anibarro, Jose M. Barcala, Maria L. De Souza-Galvao, Paloma Gijon, Rafael Luque, Francesca Sanchez
Summary: This study aims to evaluate three short-course rifamycin-based regimens for the treatment of latent tuberculosis (TB) in patients with end-stage kidney disease (ESKD). The results of this study will contribute to evidence-based recommendations for the management of latent TB infection in ESKD patients.
Article
Immunology
Anthony T. Podany, Michelle Pham, Erin Sizemore, Neil Martinson, Wadzanai Samaneka, Lerato Mohapi, Sharlaa Badal-Faesen, Rod Dawson, John L. Johnson, Harriet Mayanja, Umesh Lalloo, William C. Whitworth, April Pettit, Kayla Campbell, Patrick P. J. Phillips, Kia Bryant, Nigel Scott, Andrew Vernon, Ekaterina Kurbatova, Richard E. Chaisson, Susan E. Dorman, Payam Nahid, Susan Swindells, Kelly E. Dooley, Courtney Fletcher
Summary: This study evaluated the impact of tuberculosis treatment containing high-dose daily rifapentine on the pharmacokinetics of efavirenz-based antiretroviral therapy and viral suppression in HIV-infected individuals. The results showed that the rifapentine-based treatment modestly decreased efavirenz clearance but still met therapeutic targets, supporting its use without dose adjustment.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Priya Singh, Lawrence H. Moulton, Grace L. Barnes, Amita Gupta, Reginah Msandiwa, Richard E. Chaisson, Neil A. Martinson
Summary: Pregnancy is common among women with HIV who have received tuberculosis preventive therapy, and it is more frequent in women who have received rifamycin-isoniazid-based regimens compared to isoniazid monotherapy.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Microbiology
Michelle M. Pham, Anthony T. Podany, Noluthando Mwelase, Khuanchai Supparatpinyo, Lerato Mohapi, Amita Gupta, Wadzanai Samaneka, Ayotunde Omoz-Oarhe, Deborah Langat, Constance A. Benson, Richard E. Chaisson, Susan Swindells, Courtney Fletcher
Summary: This study evaluated the pharmacokinetics of rifapentine in HIV-infected patients receiving antiretroviral therapy and compared weight-based dosing with fixed dosing through simulations. The result supports the use of a fixed dose of rifapentine 600mg daily for TB prevention in PLWH, regardless of their weight, and no dose adjustment is needed when co-administered with efavirenz-based ART.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Riti Sharan, Shashank R. Ganatra, Dhiraj K. Singh, Journey Cole, Taylor W. Foreman, Rajesh Thippeshappa, Charles A. Peloquin, Vinay Shivanna, Olga Gonzalez, Cheryl L. Day, Neel R. Gandhi, Edward J. Dick Jr, Shannan Hall-Ursone, Smriti Mehra, Larry S. Schlesinger, Jyothi Rengarajan, Deepak Kaushal
Summary: The study found that 3HP treatment significantly reduced the infection of Mycobacterium tuberculosis and prevented reactivation of tuberculosis in latently infected macaques.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Infectious Diseases
Gail B. Cross, Intan P. Sari, Cissy Kityo, Qingshu Lu, Yogesh Pokharkar, Rajesh B. Moorakonda, Han -Nguyen Thi, Quyet Do, Victoria B. Dalay, Emmanuel Gutierrez, Vincent M. Balanag, Randy J. Castillo, Henry Mugerwa, Felic Fanusi, Philip Kwan, Ka Lip Chew, Nicholas Paton, ROSETTA trial team
Summary: This study investigated the safety and efficacy of adjunctive rosuvastatin in people with tuberculosis, and the results showed that adjunctive rosuvastatin did not produce substantial benefits on culture conversion in the overall study population.
LANCET INFECTIOUS DISEASES
(2023)
Article
Respiratory System
Henan Xin, Xuefang Cao, Haoran Zhang, Boxuan Feng, Ying Du, Bin Zhang, Dakuan Wang, Zisen Liu, Ling Guan, Fei Shen, Xueling Guan, Jiaoxia Yan, Yijun He, Yongpeng He, Zhusheng Quan, Shouguo Pan, Jianmin Liu, Qi Jin, Lei Gao
Summary: The study suggests that the 6-week twice-weekly regimen of rifapentine plus isoniazid for LTBI treatment could be an optional tool for TB control in the Chinese population.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Immunology
Jyoti S. Mathad, Rada Savic, Paula Britto, Priya Jayachandran, Lubbe Wiesner, Grace Montepiedra, Jennifer Norman, Nan Zhang, Ellen Townley, Nahida Chakhtoura, Sarah Bradford, Sandesh Patil, Stephanie Popson, Tsungai Chipato, Vanessa Rouzier, Deborah Langat, Amphan Chalermchockcharoentkit, Portia Kamthunzi, Amita Gupta, Kelly E. Dooley
Summary: The 3HP regimen is safe and effective for preventing tuberculosis in pregnant women without requiring dose adjustment, achieving target concentrations of rifapentine and isoniazid. The study supports larger safety-focused trials of 3HP in pregnancy.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Microbiology
Jiaqi Cheng, Jun Yan, Zeferino Reyna, Matt Slarve, Peggy Lu, Brad Spellberg, Brian Luna
Summary: The study found that rifabutin and colistin showed synergistic effects in combating Acinetobacter baumannii, with low-dose colistin significantly suppressing the emergence of rifabutin resistance. This combination presents a promising therapeutic option for highly resistant A. baumannii infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Medicine, Research & Experimental
Bidisha Bhattacharya, Shiqi Xiao, Sujoy Chatterjee, Michael Urbanowski, Alvaro Ordonez, Elizabeth A. Ihms, Garima Agrahari, Shichun Lun, Robert Berland, Alexander Pichugin, Yuanwei Gao, John Connor, Alexander R. Ivanov, Bo-Shiun Yan, Lester Kobzik, Bang-Bon Koo, Sanjay Jain, William Bishai, Igor Kramnik
Summary: The mechanism behind the development of necrotic granulomas in Mycobacterium tuberculosis-infected mice with sst1-susceptible genotype involves aberrant macrophage responses to TNF, leading to ISR induction through JNK/IFN-beta/PKR circuit and subsequently driving necrosis. Treatment with ISRIB inhibitor can block necrosis development in lung granulomas and reduce bacterial burden, suggesting a potential novel host-directed therapy strategy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Cell Biology
Elizabeth A. Thompson, Katherine Cascino, Alvaro A. Ordonez, Weiqiang Zhou, Ajay Vaghasia, Anne Hamacher-Brady, Nathan R. Brady, Im-Hong Sun, Rulin Wang, Avi Z. Rosenberg, Michael Delannoy, Richard Rothman, Katherine Fenstermacher, Lauren Sauer, Kathyrn Shaw-Saliba, Evan M. Bloch, Andrew D. Redd, Aaron A. R. Tobian, Maureen Horton, Kellie Smith, Andrew Pekosz, Franco R. D'Alessio, Srinivasan Yegnasubramanian, Hongkai Ji, Andrea L. Cox, Jonathan D. Powell
Summary: The study identifies a unique population of T cells expressing increased VDAC1 in severe and recovered COVID-19 patients, associated with mitochondrial dysfunction and apoptosis. Additionally, specific metabolic phenotypes of myeloid-derived suppressor cells in COVID-19 patients can distinguish between severe and mild disease. These findings offer insight into dysfunctional immune response in COVID-19 patients and potential for developing personalized therapeutic approaches.
Article
Cell Biology
Alvaro A. Ordonez, Luz M. Wintaco, Filipa Mota, Andres F. Restrepo, Camilo A. Ruiz-Bedoya, Carlos F. Reyes, Luis G. Uribe, Sudhanshu Abhishek, Franco R. D'Alessio, Daniel P. Holt, Robert F. Dannals, Steven P. Rowe, Victor R. Castillo, Martin G. Pomper, Ulises Granados, Sanjay K. Jain
Summary: F-18-FDS is a PET technology that can selectively detect Enterobacterales infections, providing safe and rapid localization of infections, differentiation of different strains, and monitoring of antibiotic efficacy. Additionally, the research demonstrates the value of F-18-FDS in differentiating diseases such as complications of COVID-19.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Brett M. Babin, Gabriela Fernandez-Cuervo, Jessica Sheng, Ori Green, Alvaro A. Ordonez, Mitchell L. Turner, Laura J. Keller, Sanjay K. Jain, Doron Shabat, Matthew Bogyo
Summary: FLASH is a fast, luminescent, and affordable sensor developed for detecting and monitoring drug susceptibility of Mycobacterium tuberculosis (Mtb). It is selective for the Mtb protease Hip1 and can detect low amounts of Mtb cells with high sensitivity within minutes. FLASH can distinguish live from dead cells and has the potential to enhance TB diagnostics and drug resistance monitoring in resource-limited settings.
ACS CENTRAL SCIENCE
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Giacomo Pirovano, Alvaro A. Ordonez, Sanjay K. Jain, Thomas Reiner, Laurence S. Carroll, Naga Vara Kishore Pillarsetty
Summary: This study developed a SARS-CoV-2 detection system based on a specific radiolabeled antibody and a separation membrane, which can directly detect viral load in biological samples. The system has high sensitivity and reliability, making it suitable for population testing, and the technology can be easily deployed to countries with limited resources for COVID-19 diagnosis.
NUCLEAR MEDICINE AND BIOLOGY
(2021)
Review
Infectious Diseases
Nicholas Skandalis, Marlene Maeusli, Dimitris Papafotis, Sarah Miller, Bosul Lee, Ioannis Theologidis, Brian Luna
Summary: Antibiotic resistance is a global health issue, mainly due to agricultural use and contamination. Research has broadened its focus on the transmission of antibiotics from pathogens to commensal bacteria, and from farms to clinical settings.
Article
Microbiology
Bosul Lee, Jun Yan, Amber Ulhaq, Sarah Miller, Wonjae Seo, Peggy Lu, Rosemary She, Brad Spellberg, Brian Luna
Summary: The antimicrobial activity of rifabutin against Acinetobacter baumannii is best modeled by using RPMI for in vitro testing. The hypersusceptibility of A. baumannii to rifabutin was observed both in vitro and in vivo using a Galleria mellonella infection model. Resistance emergence frequency was higher in vitro when bacteria were selected on RPMI compared to TSA or MHII plates, but lower in vivo compared to the RPMI in vitro condition.
Article
Medicine, Research & Experimental
Alvaro A. Ordonez, Matthew F. L. Parker, Robert J. Miller, Donika Plyku, Camilo A. Ruiz-Bedoya, Elizabeth W. Tucker, Justin M. Luu, Dustin A. Dikeman, Wojciech G. Lesniak, Daniel P. Holt, Robert F. Dannals, Lloyd S. Miller, Steven P. Rowe, David M. Wilson, Sanjay K. Jain
Summary: This study successfully used C-11-PABA PET imaging to accurately detect and monitor pyogenic bacterial infections in multiple clinically relevant animal models. It also demonstrated the potential clinical translation of C-11-PABA for detecting and localizing a broad range of bacteria.
Article
Microbiology
Jianhao Lai, Swati Shah, Rekeya Knight, Neysha Martinez-Orengo, Reema Patel, Amelia Mitchell, Zeping Wang, Falguni Basuli, Alvaro A. Ordonez, Sanjay K. Jain, Dima A. Hammoud
Summary: The diagnosis of fungal infections, especially with Aspergillus fumigatus, is still challenging. The study found low uptake of the newly described Enterobacterales imaging ligand FDS by A. fumigatus, suggesting that FDS is not a suitable imaging agent for Aspergillus.
Article
Biology
Alvaro A. Ordonez, C. Korin Bullen, Andres F. Villabona-Rueda, Elizabeth A. Thompson, Mitchell L. Turner, Vanessa F. Merino, Yu Yan, John Kim, Stephanie L. Davis, Oliver Komm, Jonathan D. Powell, Franco R. D'Alessio, Robert H. Yolken, Sanjay K. Jain, Lorraine Jones-Brando
Summary: This study evaluated the antiviral activity of sulforaphane (SFN) against SARS-CoV-2 and found that SFN can inhibit the replication of multiple strains of SARS-CoV-2 and seasonal coronaviruses. Prophylactic SFN treatment can reduce viral load, lung injury, and immune cell activation in infected mice.
COMMUNICATIONS BIOLOGY
(2022)
Article
Microbiology
Sarah Miller, Kristine Goy, Rosemary She, Brad Spellberg, Brian Luna
Summary: The antimicrobial susceptibility testing (AST) conducted in RPMI 1640, a more physiologically relevant culture medium, revealed that a significant proportion of carbapenem-resistant Acinetobacter baumannii isolates were susceptible to azithromycin, a macrolide antibiotic not commonly considered effective against A. baumannii. In vitro experiments using Galleria mellonella validated these findings. The use of RPMI 1640 as an AST culturing condition also showed superior predictive accuracy for in vivo outcomes compared to Mueller-Hinton II broth.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Matthew Slarve, Zeferino Reyna, Elizabeth Burk, Juan Ruiz-Delgado, Rachel Li, Jun Yan, Brian Luna, Brad Spellberg
Summary: Researchers have identified the antibody MAb5, which demonstrates broad binding against both U.S. and international isolates of A. baumannii and shows protective efficacy in vivo.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Stefanie Krug, Pankaj Prasad, Shiqi Xiao, Shichun Lun, Camilo A. A. Ruiz-Bedoya, Mariah Klunk, Alvaro A. A. Ordonez, Sanjay K. K. Jain, Geetha Srikrishna, Igor Kramnik, William R. R. Bishai
Summary: Despite advances in TB drug development, multidrug resistance remains a major challenge for global TB control. Host-directed therapies, such as inhibition of the integrated stress response (ISR), have the potential to improve the efficacy of tuberculosis antibiotics. In this study, we evaluated the impact of ISR inhibition on bacterial clearance, relapse, and lung pathology in a mouse model of TB. Our findings suggest that adjunctive ISR inhibition can accelerate bacterial clearance, reduce relapse rates, and improve lung health.