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Ansari MS, Zohib M, Kumari M, Yadav V, Pal RK, Tripathi S, Jain A, Biswal BK, Arora A. Structural and biophysical characterization of PadR family protein Rv0047c of Mycobacterium tuberculosis H37Rv. J Struct Biol 2025; 217:108211. [PMID: 40403899 DOI: 10.1016/j.jsb.2025.108211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 04/22/2025] [Accepted: 05/19/2025] [Indexed: 05/24/2025]
Abstract
The members of the PadR family of transcriptional regulators are important for cell survival in toxic environments and play an important role in detoxification, pathogenicity, and multi-drug resistance. Rv0047c of Mycobacterium tuberculosis H37Rv is annotated as a PadR family protein. We have characterized the stability and structure of Rv0047c. Rv0047c forms a stable dimer in solution. Its stability is characterized by a thermal melting transition temperature (Tm) of 55.3 °C. The crystal structure of Rv0047c was determined at a resolution of 3.15 Å. The structure indicates the biological unit to be a dimer with each monomer having a characteristic N-terminal winged-helix-turn-helix DNA binding domain and a C-terminal dimerization domain. The N-terminal domain is composed of four helices, α1, α2, α3, and α4 and two beta strands β1 and β2. The C-terminal dimerization domain (CTD) consists two long helices α6 and α7. The two domains are connected by helix α5. A short helical turn (helix αa, residue 89-92), leads to compaction of the α4-α5 loop. Rv0047c exhibits specificity in binding to an upstream region having an inverted repeat sequence. This binding is dependent upon Y18 and Y40 residue of Rv0047c, which are highly conserved among the PadR family. Overall, our results suggest a transcription regulatory role for Rv0047c, similar to other PadR family proteins.
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Affiliation(s)
- Md Samsuddin Ansari
- Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Muhammad Zohib
- Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Meera Kumari
- Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India
| | - Vikash Yadav
- Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Ravi Kant Pal
- X-ray Crystallography Facility, National Institute of Immunology, New Delhi 110067, India
| | - Sarita Tripathi
- Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India
| | - Anupam Jain
- Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India
| | - Bichitra Kumar Biswal
- X-ray Crystallography Facility, National Institute of Immunology, New Delhi 110067, India
| | - Ashish Arora
- Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Diriba G, Alemu A, Yenew B, Ayano BZ, Hailu M, Buta B, Wondimu A, Tefera Z, Meaza A, Seid G, Getahun M, Dagne B, Mollalign H, Abebaw Y, Getu M, Tadesse M, Belhu T, Alemu E, Demissie M, Erresso A, Aga G, Kumsa A, Letta T, Abdella S, Moga S, Dangisso MH, Tollera G, Tadesse G. Second-line drug resistance among multidrug-resistant tuberculosis patients in Ethiopia: A laboratory-based surveillance. J Glob Antimicrob Resist 2025; 42:167-174. [PMID: 39988072 DOI: 10.1016/j.jgar.2025.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 02/03/2025] [Accepted: 02/14/2025] [Indexed: 02/25/2025] Open
Abstract
OBJECTIVES To estimate the proportion of second-line anti-tuberculosis drug resistance among multidrug-resistant tuberculosis (MDR-TB) patients in Ethiopia. METHODOLOGY A laboratory-based prospective cross-sectional study was conducted at the National Tuberculosis Reference Laboratory (NTRL), Ethiopia, from February 2022 to July 2024. Phenotypic drug susceptibility testing (pDST) assessed resistance to various second-line antituberculosis drugs. The collected data were entered into Microsoft Excel 2016 and imported into Statistical Package for Social Sciences (SPSS) version 23 for descriptive analysis. RESULT Of 468 MDR-TB patients, 262 were new, and 206 were previously treated cases. Pre-extensively drug-resistant tuberculosis (pre-XDR-TB) was identified in four (1.52%) new cases and seven (3.40%) previously treated cases. Extensively drug-resistant tuberculosis (XDR-TB) was detected in three (1.15%) new cases and two (0.97%) previously treated cases. Overall, 11 (2.35%) cases were classified as pre-XDR-TB, and five (1.07%) as XDR-TB. Combined resistance to fluoroquinolones (FQs) and bedaquiline were detected in four cases (0.85%), comprising three new cases (1.15%) and one previously treated case (0.49%). Resistance to both FQs and linezolid was detected in a single previously treated case (0.49%) and acquired resistance to second-line drugs was identified in four cases. CONCLUSIONS Our study showed a prevalence of 2.35% for pre-XDR-TB and 1.07% for XDR-TB among MDR-TB cases, highlighting the importance of continuous surveillance and tailored treatment approaches to control the spread of drug-resistant TB (DR-TB) in Ethiopia. Future studies on MDR-TB surveillance should prioritize the integration of genomic surveillance into routine laboratory-based DR-TB monitoring systems to enhance early detection of resistance patterns, support targeted treatment strategies, and improve overall patient management efforts.
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Affiliation(s)
- Getu Diriba
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
| | - Ayinalem Alemu
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia; Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Bazezew Yenew
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | | | - Michael Hailu
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Bedo Buta
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | | | - Zigba Tefera
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Abyot Meaza
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Getachew Seid
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | | | - Biniyam Dagne
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | | | | | - Melak Getu
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | | | - Tegegn Belhu
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Ephrem Alemu
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | | | | | - Getachew Aga
- Ministry of Health, National TB, Leprosy and other Lung Diseases Control Program, Addis Ababa, Ethiopia
| | - Andargachew Kumsa
- Ministry of Health, National TB, Leprosy and other Lung Diseases Control Program, Addis Ababa, Ethiopia
| | - Taye Letta
- Ministry of Health, National TB, Leprosy and other Lung Diseases Control Program, Addis Ababa, Ethiopia
| | - Saro Abdella
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Shewki Moga
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
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Aranaga C, Varela R, Falco A, Villa J, Moreno LM, Causse M, Martínez-Martínez L. In Vitro Activity of the Triazinyl Diazepine Compound FTSD2 Against Drug-Resistant Mycobacterium tuberculosis Strains. Pharmaceuticals (Basel) 2025; 18:360. [PMID: 40143137 PMCID: PMC11945624 DOI: 10.3390/ph18030360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 02/27/2025] [Accepted: 02/28/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: Compounds derived from pyrimido-diazepine have shown selective inhibition of the susceptible Mycobacterium tuberculosis strain H37Rv. However, there is a need for studies that evaluate the activity of these compounds against multidrug-resistant strains and clinical isolates. This study aims to evaluate the antitubercular potential of FTSD2 against drug-resistant strains of M. tuberculosis. Methods: The compound 4-(2,4-diamino-8-(4-methoxyphenyl)-8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepin-6-yl)-N-(2-(4-(dimethylamino)-6-(4-fluorophenyl)amino-1,3,5-triazin-2-yl)amino)ethyl)benzenesulfonamide (FTSD2) was tested against drug-resistant M. tuberculosis strains at minimal inhibitory and bactericidal concentrations (MIC and MBC). Kill curve assays were performed to assess bactericidal activity, and cytotoxicity was evaluated in human monocyte-derived macrophages and the RAW 264.7 murine macrophage cell line. Intracellular death assays, specifically macrophage infection assays, were also conducted to evaluate the effect of FTSD2 on intracellular M. tuberculosis growth. Results: FTSD2 inhibited the growth of drug-resistant M. tuberculosis at MIC and MBC values between 0.5 and 1 mg/L. Kill curve assays demonstrated concentration-dependent bactericidal activity. No cytotoxicity was observed in macrophages at concentrations below 64 mg/L. Additionally, FTSD2 significantly suppressed intracellular M. tuberculosis growth after 192 h. FTSD2 did not inhibit the growth of nontuberculous mycobacteria, including M. avium, M. abscessus, M. fortuitum, M. chelonae, and M. smegmatis at 50 mg/L. Conclusions: FTSD2 exhibits strong potential as a leading compound for the development of new antitubercular drugs, with selective activity against M. tuberculosis and minimal cytotoxic effects on macrophages. Further studies are needed to explore its mechanisms of action and therapeutic potential.
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Affiliation(s)
- Carlos Aranaga
- Grupo de Investigación en Química y Biotecnología (QUIBIO), Facultad de Ciencias Básicas, Laboratorio de Parasitología y Enfermedades Tropicales, Universidad Santiago de Cali, Santiago de Cali 760035, Colombia;
- Departamento de Química Agrícola, Edafología y Microbiología, Universidad de Córdoba, 14071 Córdoba, Spain;
| | - Ruben Varela
- Grupo de Investigación en Química y Biotecnología (QUIBIO), Facultad de Ciencias Básicas, Laboratorio de Parasitología y Enfermedades Tropicales, Universidad Santiago de Cali, Santiago de Cali 760035, Colombia;
| | - Aura Falco
- Grupo de Investigación en Microbiología, Industria y Medio Ambiente (GIMIA), Facultad de Ciencias Básicas, Universidad Santiago de Cali, Santiago de Cali 760035, Colombia;
| | - Janny Villa
- Grupo de Investigaciones Biomédicas, Facultad de Ciencias de la Salud, Corporación Universitaria Remington, Medellín 0500, Colombia;
| | - Leydi M. Moreno
- Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, Santiago de Cali 760042, Colombia;
| | - Manuel Causse
- Unidad de Gestión Clínica de Microbiología, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain;
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFECT), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Luis Martínez-Martínez
- Departamento de Química Agrícola, Edafología y Microbiología, Universidad de Córdoba, 14071 Córdoba, Spain;
- Unidad de Gestión Clínica de Microbiología, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain;
- Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFECT), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Maani AA, Petersen E, Memish ZA. The critical role of new tuberculosis vaccines in achieving the WHO 2035 End TB target. IJID REGIONS 2025; 14:100595. [PMID: 40201559 PMCID: PMC11973680 DOI: 10.1016/j.ijregi.2025.100595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 01/30/2025] [Accepted: 01/31/2025] [Indexed: 04/10/2025]
Abstract
This perspective article, in recognition of World TB Day 2025, highlights the essential role that new tuberculosis (TB) vaccines play in meeting the World Health Organization's goal of ending TB by 2035. The article does not provide a comprehensive review of all vaccine candidates but emphasizes the urgent need for novel TB vaccines, given the limitations of the bacillus Calmette-Guérin vaccine and the increasing threat of drug-resistant strains. As TB continues to be a leading cause of global morbidity and mortality, with an estimated 10.8 million new cases in 2023, it is evident that current strategies are insufficient. Although advancements in vaccine research, including candidates such as M72/AS01E, show promise, the article underscores that achieving TB elimination requires vaccines that can prevent TB infection reactivation and transmission of drug-resistant strains. Overcoming scientific, logistical, and distribution challenges, particularly, in high-burden regions, will be critical to accelerating the availability of these vaccines. The article calls for intensified global collaboration and sustained investment in research to accelerate the development of novel vaccines, which are indispensable for reaching the World Health Organization's ambitious 2035 TB elimination targets.
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Affiliation(s)
- Amal Al Maani
- Centre for diseases control and prevention, Ministry of Health, Muscat, Oman
- International Society for Infectious Diseases, Massachusetts, USA
| | - Eskild Petersen
- International Society for Infectious Diseases, Massachusetts, USA
- Institute for Clinical Medicine, Faculty of Health Science, University of Aarhus, Aarhus, Denmark
- PandemiX Center, Department of Science and Environment, Roskilde University, Roskilde, Denmark
| | - Ziad A. Memish
- College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
- King Salman Humanitarian Aid & Relief Centre, Riyadh, Kingdom of Saudi Arabia
- Abu Dhabi University, Abu Dhabi, United Arab Emirates
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Hailu BK, Demessie Y, Gessese AT, Dagnaw GG, Dejene H. Multidrug Resistance Tuberculosis in the Context of Co-Infection in Ethiopia: A Systematic Review and Meta-Analysis. J Epidemiol Glob Health 2025; 15:19. [PMID: 39909956 PMCID: PMC11799485 DOI: 10.1007/s44197-025-00360-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 12/16/2024] [Indexed: 02/07/2025] Open
Abstract
The rise of multidrug-resistant tuberculosis (MDR-TB) remains a critical public health challenge, particularly in developing countries like Ethiopia. This systematic review and meta-analysis aimed to estimate the pooled prevalence of MDR-TB with co-infections and assess its effects among different co-infections in Ethiopia. The systematic review and meta-analysis were conducted from August to October 2024. The study adhered to PRISMA guidelines and utilized various academic databases including PubMed, Web of Science and Science Direct to identify relevant articles. To check for publication bias and small study effects, a funnel plot and Egger's test were employed. The statistical analysis was performed with R software version 4.4.1. From an original pool of 6,461 papers, 15 studies published between 2014 and 2024 were considered after applying certain inclusion and exclusion criteria. The analysis revealed an overall pooled prevalence of MDR-TB in the context of co-infections at 20% (95% CI: 14.0-26.0). Notably, the prevalence was higher among individuals with HIV co-infection at 23.2% (95% CI: 18.3-28.0), while it was lower in those with diabetes co-infection at 10% (95% CI: 3.0-17.3). The study found significant heterogeneity among the reported prevalence rates (I² = 94.93%, p < 0.001). These findings highlight the complex interplay between MDR-TB and other co-infections, posing significant challenges for clinical management and public health in Ethiopia. To enhance health outcomes and curb the spread of MDR-TB, government and public health authorities must implement targeted interventions, including monitoring and treatment programs in high-prevalence areas.
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Affiliation(s)
- Bezawit Kassaw Hailu
- Department of Veterinary Epidemiology and Public Health, College of Veterinary Medicine and Animal Science, University of Gondar, P.O. Box 196, Gondar, Ethiopia
| | - Yitayew Demessie
- Department of Biomedical Sciences, College of Veterinary Medicine and Animal Science, University of Gondar, P.O. Box 196, Gondar, Ethiopia
| | - Abebe Tesfaye Gessese
- Department of Biomedical Sciences, College of Veterinary Medicine and Animal Science, University of Gondar, P.O. Box 196, Gondar, Ethiopia
| | - Gashaw Getaneh Dagnaw
- Department of Biomedical Sciences, College of Veterinary Medicine and Animal Science, University of Gondar, P.O. Box 196, Gondar, Ethiopia
| | - Haileyesus Dejene
- Department of Veterinary Epidemiology and Public Health, College of Veterinary Medicine and Animal Science, University of Gondar, P.O. Box 196, Gondar, Ethiopia.
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Raqib R, Sarker P. Repurposed Drugs and Plant-Derived Natural Products as Potential Host-Directed Therapeutic Candidates for Tuberculosis. Biomolecules 2024; 14:1497. [PMID: 39766204 PMCID: PMC11673177 DOI: 10.3390/biom14121497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 11/15/2024] [Accepted: 11/22/2024] [Indexed: 01/11/2025] Open
Abstract
Tuberculosis (TB) is one of the leading causes of death due to infectious disease. It is a treatable disease; however, conventional treatment requires a lengthy treatment regimen with severe side effects, resulting in poor compliance among TB patients. Intermittent drug use, the non-compliance of patients, and prescription errors, among other factors, have led to the emergence of multidrug-resistant TB, while the mismanagement of multidrug-resistant TB (MDR-TB) has eventually led to the development of extensively drug-resistant tuberculosis (XDR-TB). Thus, there is an urgent need for new drug development, but due to the enormous expenses and time required (up to 20 years) for new drug research and development, new therapeutic approaches to TB are required. Host-directed therapies (HDT) could be a most attractive strategy, as they target the host defense processes instead of the microbe and thereby may prevent the alarming rise of MDR- and XDR-TB. This paper reviews the progress in HDT for the treatment of TB using repurposed drugs which have been investigated in clinical trials (completed or ongoing) and plant-derived natural products that are in clinical or preclinical trial stages. Additionally, this review describes the existing challenges to the development and future research directions in the implementation of HDT.
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Affiliation(s)
- Rubhana Raqib
- Immunobiology, Nutrition and Toxicology Unit, Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh;
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Moe S, Azamat I, Allamuratova S, Oluya M, Khristusev A, Rekart ML, Mamitova K, Bidwell G, Gomez-Restrepo C, Kalmuratov B, Tigay Z, Parpieva N, Safaev K, Sitali N, Gomez D, Mikhail A, Sinha A. Second-line drug-resistant TB and associated risk factors in Karakalpakstan, Uzbekistan. IJTLD OPEN 2024; 1:391-397. [PMID: 39301133 PMCID: PMC11409172 DOI: 10.5588/ijtldopen.24.0351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 07/10/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Drug-resistant TB (DR-TB) remains a major public health threat. In 2022, Uzbekistan reported 2,117 cases of DR-TB, with 69% tested for fluoroquinolone resistance. Limited information is available on the prevalence of resistance to bedaquiline, linezolid, and fluoroquinolone, which are key components of the all-oral treatment regimen for rifampicin-resistant TB in Uzbekistan. METHODS A retrospective study was conducted using extensive programmatic data from 2019 to 2023 in Uzbekistan. We assessed second-line drug-resistant TB (SLDR-TB) rates using phenotypic drug susceptibility testing (pDST). Demographic and clinical characteristics associated with SLDR-TB were analysed using multivariable logistic regression models based on the Allen-Cady approach. RESULTS In total, 2,405 patients with TB who had undergone pDST were included (median age 40 years, 47% female). The overall SLDR-TB resistance rate was 24% (95% CI 22-26). Prevalence of resistance to bedaquiline, linezolid, moxifloxacin, levofloxacin, and amikacin were respectively 3.1%, 0.8%, 15%, 13%, and 12%. Risk factors for SLDR-TB were resistance to rifampicin and/or isoniazid, exposure to clofazimine, retreatment status, contact with drug-susceptible TB case or DR-TB case, and diabetes. CONCLUSIONS The high prevalence of SLDR-TB is of major concern, emphasising the need for baseline pDST in RR-TB treatment. Identified risk factors can aid early detection of at-risk individuals and inform clinical practice.
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Affiliation(s)
- S Moe
- Médecins Sans Frontières (MSF), Nukus, Uzbekistan
| | - I Azamat
- Médecins Sans Frontières (MSF), Nukus, Uzbekistan
| | | | - M Oluya
- Médecins Sans Frontières (MSF), Nukus, Uzbekistan
| | - A Khristusev
- Médecins Sans Frontières (MSF), Nukus, Uzbekistan
| | - M L Rekart
- Médecins Sans Frontières (MSF), Nukus, Uzbekistan
| | - K Mamitova
- Médecins Sans Frontières (MSF), Nukus, Uzbekistan
| | - G Bidwell
- Médecins Sans Frontières (MSF), Nukus, Uzbekistan
| | | | - B Kalmuratov
- Republican Center of Tuberculosis and Pulmonology, Nukus, Uzbekistan
| | - Z Tigay
- Republican Center of Tuberculosis and Pulmonology, Nukus, Uzbekistan
| | - N Parpieva
- Republican Specialised Scientific and Practical Medical Center of Tuberculosis and Pulmonology, Tashkent, Uzbekistan
| | - K Safaev
- Republican Specialised Scientific and Practical Medical Center of Tuberculosis and Pulmonology, Tashkent, Uzbekistan
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Joshi P, Singh KG, Patidar V, Gupta V. Evaluation of Diagnostic Methods and Rifampicin Resistance in Pulmonary Tuberculosis: A Hospital-Based Study. Cureus 2024; 16:e67062. [PMID: 39286711 PMCID: PMC11403642 DOI: 10.7759/cureus.67062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2024] [Indexed: 09/19/2024] Open
Abstract
Background Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, predominantly affecting the lungs (pulmonary TB) and is a significant public health challenge in India. The study aims to analyze demographic, radiological, and clinical subgroups of pulmonary TB cases, examine the relationship between smear acid-fast bacillus (AFB examination) and cartridge-based nucleic acid amplification test (CBNAAT), evaluate CBNAAT sensitivity for Mycobacterium tuberculosis (MTB) in new and previously treated patients, and determine the proportion of rifampicin resistance. Methods This hospital-based prospective study was conducted among patients diagnosed with pulmonary TB at the Respiratory Medicine Department of a Government Hospital over 16 months (August 2019 to December 2020). The study included 150 diagnosed TB cases (new and previously treated). Data collection encompassed demographic details, clinical symptoms, comorbidities, radiological findings (chest X-ray), and microbiological results (smear AFB examination, CBNAAT). Sputum samples were subjected to Ziehl-Neelsen staining and CBNAAT for MTB detection and rifampicin resistance testing. Statistical analysis was performed using IBM SPSS Statistics version 21.0 (IBM Corp., Armonk, NY, USA). Results Of the 150 patients, 69.3% were male, and 48% were aged 21-40 years. The majority had a BMI of 18.5-24.9 kg/m² (50%) and resided in urban areas (63.3%). Common symptoms included cough (95.3%), fever (80%), and weight loss (74%). Cavitary lesions on chest X-ray were observed in 84% of patients. Smear microscopy detected MTB in 72.7% of cases, while CBNAAT detected MTB in 94% of cases. CBNAAT sensitivity for smear-positive and smear-negative samples was 93.97% and 94.12%, respectively. Rifampicin resistance was found in 3% of new cases and 6% of previously treated cases. The sensitivity of smear microscopy was 77.33%, and the sensitivity of CBNAAT was 94%. Conclusion The study underscores the high burden of pulmonary TB and the utility of CBNAAT in detecting MTB and rifampicin resistance, particularly in smear-negative samples. The findings highlight the necessity of universal drug susceptibility testing (DST) for effective TB management and the importance of addressing drug resistance to improve treatment outcomes.
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Affiliation(s)
- Priyanka Joshi
- Pulmonary Medicine, Mahaveer Institute of Medical Sciences and Research, Bhopal, IND
| | - Krishna G Singh
- Respiratory Medicine, Chirayu Medical College and Hospital, Bhopal, IND
| | - Vishal Patidar
- Respiratory Medicine, Amaltas Institute of Medical Sciences, Bangar Dewas, IND
| | - Vikas Gupta
- Community Medicine, Government Medical College, Seoni, IND
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Chen YL, Xie YQ, Wei MY, Xu DM. Clinical effects of detailed nursing management interventions on medication adherence and disease perception in patients with drug-resistant tuberculosis. World J Clin Cases 2024; 12:4191-4198. [PMID: 39015906 PMCID: PMC11235556 DOI: 10.12998/wjcc.v12.i20.4191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 05/16/2024] [Accepted: 05/29/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Tuberculosis (TB) is a chronic respiratory infectious disease that considerably jeopardizes human health, and there is no effective vaccine suitable for its prevention in the entire population. AIM To investigate the promotion of medication adherence and disease cognition in patients with drug-resistant (DR-)TB using detailed nursing management. METHODS In total, 114 patients with DR-TB who were diagnosed and treated at our hospital between January 2019 and January 2023 were included in this study. Patients in the control group (n = 57) were managed with conventional nursing care, while those in the observation group (n = 57) were managed with detailed nursing care. Medication adherence, disease awareness scores, medication safety, and nursing satisfaction were compared between the two groups after the intervention. RESULTS The post-intervention medication compliance rate was 91.23% in the observation group and 75.44% in the control group, with the former being 15.79% higher than the latter (P < 0.05). There was no statistically significant difference in the disease awareness scores between the two groups before the intervention; the disease awareness scores of the observation group were significantly higher than those of the control group after the intervention (P < 0.05). The incidence of gastrointestinal reactions, joint swelling and pain, hearing loss, electrolyte disorders, and liver and kidney function abnormalities were lower in the observation group than those in the control group. The total nursing satisfaction of the observation group was higher than that of the control group (P < 0.05). CONCLUSION Implementation of detailed nursing management for patients with DR-TB can effectively improve medication adherence, enhance awareness of the disease, ensure safety of medication, and improve satisfaction with nursing care.
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Affiliation(s)
- Yan-Li Chen
- Nursing Department, The First People’s Hospital of Tianmen in Hubei Province, Tianmen 431700, Hubei Province, China
| | - Ya-Qin Xie
- Nursing Department, The First People’s Hospital of Tianmen in Hubei Province, Tianmen 431700, Hubei Province, China
| | - Ming-Yue Wei
- Infectious Disease Department, The First People’s Hospital of Tianmen in Hubei Province, Tianmen 431700, Hubei Province, China
| | - Dong-Mei Xu
- Nursing Department, The First People’s Hospital of Tianmen in Hubei Province, Tianmen 431700, Hubei Province, China
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Diriba G, Alemu A, Ayano BZ, Yenew B, Hailu M, Buta B, Wondimu A, Tefera Z, Ababu Z, Ebisa Y, Moga S, Tadesse G. Acquired bedaquiline and fluoroquinolones resistance during treatment follow-up in Oromia Region, North Shewa, Ethiopia. IDCases 2024; 36:e01988. [PMID: 38779144 PMCID: PMC11109312 DOI: 10.1016/j.idcr.2024.e01988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 05/01/2024] [Accepted: 05/07/2024] [Indexed: 05/25/2024] Open
Abstract
Background Bedaquiline (BDQ) is an effective drug currently used for multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB) treatment. However, resistance to this new drug is emerging. We discussed the characteristics of the first patient in Ethiopia who acquired BDQ and fluoroquinolones (FQs) resistance during treatment follow-up. Case report In this case report, we present the case of a 28-year-old male pulmonary TB patient diagnosed with MDR-TB who is a resident of the Oromia Region of North Shewa, Mulona Sululta Woreda, Ethiopia. Sputum specimen was collected initially and for treatment monitoring using culture and for phenotypic drug susceptibility testing (DST) to first-line and second-line TB drugs. Initially, the patient was infected with a mycobacterial strain resistant to the first-line anti-TB drugs Rifampicin (RIF), Isoniazid (INH), and Pyrazinamide (PZA). Later, during treatment, he acquired additional drug resistance to ethambutol (EMB), ofloxacin (OFX), levofloxacin (LFX), moxifloxacin (MFX), and BDQ. The patient was tested with MTBDRplus and MTBDRsl to confirm the presence of resistance-conferring mutation and mutation was detected in rpoB, katG, and gyrA genes. Finally, the patient was registered as having extensively drug-resistant tuberculosis (XDR-TB) and immediately started an individualized treatment regimen. Conclusion This case report data has revealed the evolution of BDQ resistance during treatment with a BDQ-containing regimen in Ethiopia. Therefore, there is a need for DST to new second-line drugs to monitor and prevent the spread of DR-TB.
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Affiliation(s)
- Getu Diriba
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Ayinalem Alemu
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Bazezew Yenew
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Michael Hailu
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Bedo Buta
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | | | - Zigba Tefera
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | | | | | - Shewki Moga
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
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Fu L, Wang W, Xiong J, Zhang P, Li H, Zhang X, Liang H, Yang Q, Wang Z, Chen X, Deng G, Cai Y, Tang S. Evaluation of Sulfasalazine as an Adjunctive Therapy in Treating Pulmonary Pre-XDR-TB: Efficacy, Safety, and Treatment Implication. Infect Drug Resist 2024; 17:595-604. [PMID: 38390619 PMCID: PMC10882277 DOI: 10.2147/idr.s443897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 02/12/2024] [Indexed: 02/24/2024] Open
Abstract
Background The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB. Methods A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment. Results Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures. Conclusion Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.
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Affiliation(s)
- Liang Fu
- Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, People's Republic of China
- Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China
| | - Wenfei Wang
- Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China
- Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, Guangdong, People's Republic of China
| | - Juan Xiong
- Health Science Center, Shenzhen University, Shenzhen, Guangdong, People's Republic of China
| | - Peize Zhang
- Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China
| | - Hui Li
- Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China
| | - Xilin Zhang
- Tuberculosis Prevention and Control Department, the Fourth People's Hospital of Foshan, Foshan, Guangdong, People's Republic of China
| | - Hancheng Liang
- Division Two of Tuberculosis Diseases Department, the Sixth People's Hospital of Dongguan, Dongguan, Guangdong, People's Republic of China
| | - Qianting Yang
- Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China
| | - Zhaoqin Wang
- Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China
| | - Xinchun Chen
- Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, Guangdong, People's Republic of China
| | - Guofang Deng
- Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China
| | - Yi Cai
- Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, Guangdong, People's Republic of China
| | - Shenjie Tang
- Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, People's Republic of China
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Fu L, Xiong J, Wang H, Zhang P, Yang Q, Cai Y, Wang W, Sun F, Zhang X, Wang Z, Chen X, Zhang W, Deng G. Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR]. BMC Infect Dis 2023; 23:834. [PMID: 38012543 PMCID: PMC10683225 DOI: 10.1186/s12879-023-08644-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 09/25/2023] [Indexed: 11/29/2023] Open
Abstract
INTRODUCTION The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs). METHODS Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients' treatment regimens are initially based on drug resistance profiles and patient's preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions. DISCUSSION Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations. TRAIL REGISTRATION Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021.
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Affiliation(s)
- Liang Fu
- Division Two of Pulmonary Diseases Department, Shenzhen Third People's Hospital, Shenzhen Clinical Research Center for Tuberculosis, National Clinical Research Center for Infectious Disease (Shenzhen), Southern University of Science and Technology, 29 Bulan Rd, Longgang District, Shenzhen, 518112, China
| | - Juan Xiong
- Health Science Center, Shenzhen University, 3688 Nanhai Avenue, Nanshan District, Shenzhen, 518060, China
| | - Haibo Wang
- Peking University Clinical Research Institute, Peking University First Hospital, Xueyuan Rd 38#, Haidian District, Beijing, 100000, 100191, China
| | - Peize Zhang
- Division Two of Pulmonary Diseases Department, Shenzhen Third People's Hospital, Shenzhen Clinical Research Center for Tuberculosis, National Clinical Research Center for Infectious Disease (Shenzhen), Southern University of Science and Technology, 29 Bulan Rd, Longgang District, Shenzhen, 518112, China
| | - Qianting Yang
- Division Two of Pulmonary Diseases Department, Shenzhen Third People's Hospital, Shenzhen Clinical Research Center for Tuberculosis, National Clinical Research Center for Infectious Disease (Shenzhen), Southern University of Science and Technology, 29 Bulan Rd, Longgang District, Shenzhen, 518112, China
| | - Yi Cai
- Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, 1066 Xueyuan Ave, Nanshan District, Shenzhen, 518060, China
| | - Wenfei Wang
- Division Two of Pulmonary Diseases Department, Shenzhen Third People's Hospital, Shenzhen Clinical Research Center for Tuberculosis, National Clinical Research Center for Infectious Disease (Shenzhen), Southern University of Science and Technology, 29 Bulan Rd, Longgang District, Shenzhen, 518112, China
- Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, 1066 Xueyuan Ave, Nanshan District, Shenzhen, 518060, China
| | - Feng Sun
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Jing'an District, Shanghai, 200040, China
| | - Xilin Zhang
- Tuberculosis Prevention and Control Department, The Fourth People's Hospital of Foshan, 106 Jinlannan Rd, Chancheng District, Foshan, 528000, China
| | - Zhaoqin Wang
- Division Two of Pulmonary Diseases Department, Shenzhen Third People's Hospital, Shenzhen Clinical Research Center for Tuberculosis, National Clinical Research Center for Infectious Disease (Shenzhen), Southern University of Science and Technology, 29 Bulan Rd, Longgang District, Shenzhen, 518112, China
| | - Xinchun Chen
- Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, 1066 Xueyuan Ave, Nanshan District, Shenzhen, 518060, China.
| | - Wenhong Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Jing'an District, Shanghai, 200040, China.
| | - Guofang Deng
- Division Two of Pulmonary Diseases Department, Shenzhen Third People's Hospital, Shenzhen Clinical Research Center for Tuberculosis, National Clinical Research Center for Infectious Disease (Shenzhen), Southern University of Science and Technology, 29 Bulan Rd, Longgang District, Shenzhen, 518112, China.
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Joshi T, Nain P, Bhamra P, Kaur J. Favorable clinical outcomes and anti-mycobacterial efficacy of pretomanid in patients with highly resistant tuberculosis: A review. Indian J Tuberc 2023; 71 Suppl 1:S130-S135. [PMID: 39067944 DOI: 10.1016/j.ijtb.2023.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 09/16/2023] [Accepted: 09/22/2023] [Indexed: 07/30/2024]
Abstract
Rising cases of drug resistance of mycobacterium species are one of the biggest concerns when the goal is to eradicate TB (Tuberculosis) from the world by the year 2030. A limited number of treatment options as MTB (Mycobacterium tuberculosis) is getting resistant to anti-mycobacterial drugs either due to a patient's non-compliance towards treatment regimen or if a patient is infected by drug-resistant species of MTB. This review aims to assess the effectiveness of pretomanid, a recently approved drug for the treatment of extensively drug-resistant TB. A thorough search of databases like PubMed, Cochrane library, CDC, Research Gate, and Google scholar was used in order to find case reports and clinical trials providing data on the efficacy of pretomanid in different drug regimens. According to research trials conducted, the drug appears to be efficacious, safe, and well-tolerable. Only headache was the most frequently observed adverse drug event, and a high dose-related increase in serum creatinine level was seen, which came to normal after the drug was discontinued.
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Affiliation(s)
- Tanishq Joshi
- Department of Pharmacy Practice, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India
| | - Parminder Nain
- Department of Pharmacy Practice, CT Institute of Pharmaceutical Sciences, Shahpur, Jalandhar, Punjab 144020, India
| | - Prajwal Bhamra
- Department of Pharmacy Practice, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India
| | - Jaspreet Kaur
- Department of Pharmacy Practice, CT Institute of Pharmaceutical Sciences, Shahpur, Jalandhar, Punjab 144020, India.
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Fu L, Zhang X, Xiong J, Sun F, Weng T, Li Y, Zhang P, Li H, Yang Q, Cai Y, Liang H, Chen Q, Wang Z, Liu L, Chen X, Zhang W, Deng G. Selecting an appropriate all-oral short-course regimen for patients with multidrug-resistant or pre-extensive drug-resistant tuberculosis in China: A multicenter prospective cohort study. Int J Infect Dis 2023; 135:101-108. [PMID: 37567554 DOI: 10.1016/j.ijid.2023.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 08/02/2023] [Accepted: 08/04/2023] [Indexed: 08/13/2023] Open
Abstract
OBJECTIVES Long, ineffective, and toxic regimens hinder the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant tuberculosis (pre-XDR-TB). METHODS We conducted a multicenter cohort study to prospectively evaluate the safety and efficacy of three 9-month, all-oral, 5-drug regimens. Regimen A (bedaquiline [Bdq]+linezolid [Lzd]+moxifloxacin [Mfx]+cycloserine [Cs]+pyrazinamide [Pza]) and Regimen B (Lzd+Mfx+Cs+clofazimine [Cfz]+Pza) were used to treat MDR-TB patients (Groups A and B, respectively, assigned according to the patient's treatment preference), while Regimen C (Bdq+Lzd+Cs+Cfz+Pza) was used to treat pre-XDR-TB patients (Group C). The primary endpoint was the occurrence of an unfavorable outcome within 12 months of treatment completion, regardless of regimen. RESULTS A total of 104 patients (34 in Group A, 46 in Group B, and 24 in Group C), with a median age of 35.5 (29.0-54.0) years, were included in the analysis population. At 12 months after treatment completion, five patients were deemed non-assessable. Of the remaining 99 participants, seven (7.1%) had an unfavorable outcome (including two deaths from any cause, four with treatment failure, and one loss to follow-up) and 92 (92.9%) had a favorable outcome. Culture conversion was achieved in 82.5% (80/97) of participants at month 2 and in 97.9% (94/97) of participants at month 6. Adverse events (AEs) resulting in drug adjustment occurred in 69.2% (72/104) of participants, mainly due to Lzd and Pza use. A QT interval prolongation of ≥ 500 ms occurred in 5.8% (6/104) of participants. CONCLUSION The primary outcome of the three tailored, 9-month, all-oral, 5-drug regimens was satisfactory in the vast majority of MDR-TB and pre-XDR-TB patients, with manageable and reversible AEs.
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Affiliation(s)
- Liang Fu
- Division Two of Pulmonary Diseases Department, National Clinical Research Center for Infectious Disease (Shenzhen), Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Xilin Zhang
- Tuberculosis Prevention and Control Department, The Fourth People's Hospital of Foshan, Foshan, China
| | - Juan Xiong
- Health Science Center, Shenzhen University, Shenzhen, China
| | - Feng Sun
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Taoping Weng
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yang Li
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Peize Zhang
- Division Two of Pulmonary Diseases Department, National Clinical Research Center for Infectious Disease (Shenzhen), Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Hui Li
- Division Two of Pulmonary Diseases Department, National Clinical Research Center for Infectious Disease (Shenzhen), Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Qianting Yang
- Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Disease, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, China
| | - Yi Cai
- Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, China
| | - Hancheng Liang
- Division Two of Tuberculosis Diseases Department, The Sixth People's Hospital of Dongguan, Dongguan, China
| | - Qiuqi Chen
- Graduate School of Guangdong Medical University, Zhanjiang, China
| | - Zhaoqing Wang
- Division Two of Pulmonary Diseases Department, National Clinical Research Center for Infectious Disease (Shenzhen), Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Lei Liu
- Division Two of Pulmonary Diseases Department, National Clinical Research Center for Infectious Disease (Shenzhen), Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Xinchun Chen
- Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Guofang Deng
- Division Two of Pulmonary Diseases Department, National Clinical Research Center for Infectious Disease (Shenzhen), Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China.
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