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Mondal S, Roy V, Meshram GG, Khanna A, Velpandian T, Garg S. Pharmacokinetics-pharmacodynamics of first-line antitubercular drugs: a comparative study in tuberculosis patients with and without concomitant diabetes mellitus. Eur J Clin Pharmacol 2024; 80:1945-1958. [PMID: 39287783 DOI: 10.1007/s00228-024-03754-x] [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: 07/13/2024] [Accepted: 08/30/2024] [Indexed: 09/19/2024]
Abstract
PURPOSE To observe the variability in the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profiles of first-line antitubercular drugs in pulmonary tuberculosis (TB) patients with and without diabetes mellitus (DM). METHODS Newly diagnosed pulmonary TB patients aged 18-60 years with or without DM were included in the study. Group I (n = 20) included patients with TB, whereas group II (n = 20) included patients with both TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. Improvements in clinical features, X-ray findings, sputum conversion, and adverse drug reactions (ADRs) were assessed after 2 months of therapy. RESULTS Isoniazid displayed non-significantly higher plasma concentrations in diabetic patients, along with a significantly (P < 0.05) longer elimination half-life (t1/2). Rifampicin plasma concentrations at 4, 8, and 12 h were significantly (P < 0.05) lower, and it displayed significantly (P < 0.05) lower area under the curve (AUC0-12 and AUC0-∞), shorter t1/2, higher clearance (Cl), and a lower AUC0-∞/MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC0-12, AUC0-∞, and t1/2 in diabetic patients. The improvements in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both groups. CONCLUSIONS The presence of DM in TB patients affects the PK-PD parameters of isoniazid, rifampicin, pyrazinamide, and ethambutol variably in the Indian population. Studies with a larger number of patients are required to further elucidate the role of DM on the PK-PD profile of first-line antitubercular drugs and treatment outcomes in TB patients with concomitant DM. TRIAL REGISTRATION CTRI/2021/08/035578 dated 11/08/2021.
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Affiliation(s)
- Sourav Mondal
- Department of Pharmacology, Maulana Azad Medical College, New Delhi, 110002, India
- Department of Clinical Pharmacology, Seth GS Medical College and King Edward Memorial Hospital, Mumbai, 400012, India
| | - Vandana Roy
- Department of Pharmacology, Maulana Azad Medical College, New Delhi, 110002, India.
| | - Girish Gulab Meshram
- Department of Pharmacology, Maulana Azad Medical College, New Delhi, 110002, India
| | - Ashwani Khanna
- TB and Chest Clinic, Lok Nayak Hospital, New Delhi, 110002, India
| | - Thirumurthy Velpandian
- Department of Ocular Pharmacology and Pharmacy Division of Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Sandeep Garg
- Department of General Medicine, Maulana Azad Medical College, New Delhi, 110002, India
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Sarkar M, Sarkar J. Therapeutic drug monitoring in tuberculosis. Eur J Clin Pharmacol 2024; 80:1659-1684. [PMID: 39240337 DOI: 10.1007/s00228-024-03749-8] [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: 05/23/2024] [Accepted: 08/26/2024] [Indexed: 09/07/2024]
Abstract
PURPOSE Therapeutic drug monitoring (TDM) is a standard clinical procedure that uses the pharmacokinetic and pharmacodynamic parameters of the drug in the body to determine the optimal dose. The pharmacokinetic variability of the drug(s) is a significant contributor to poor treatment outcomes, including the development of acquired drug resistance. TDM aids in dose optimization and improves outcomes while lessening drug toxicity. TDM is used to manage patients with tuberculosis (TB) who exhibit a slow response to therapy, despite good compliance and drug-susceptible organisms. Additional indications include patients at risk of malabsorption or delayed absorption of TB drugs and patients with drug-drug interaction and drug toxicity, which confirm compliance with therapy. TDM usually requires two blood samples: the 2 h and the 6 h post-dose. This narrative review will discuss the pharmacokinetics and pharmacodynamics of TB drugs, determinants of poor response to therapy, indications of TDM, methods of performing TDM, and its interpretations. METHODS This is a narrative review. We searched PubMed, Embase, and the CINAHL from inception to April 2024. We used the following search terms: tuberculosis, therapeutic drug monitoring, anti-TB drugs, pharmacokinetics, pharmacodynamics, limited sample strategies, diabetes and TB, HIV and TB, and multidrug-resistant TB. All types of articles were selected. RESULTS TDM is beneficial in managing TB, especially in patients with slow responses, drug-resistance TB, recurrent TB, and comorbidities such as diabetes mellitus and human immunodeficiency virus infection. CONCLUSION TDM is beneficial for improving outcomes, reducing the risk of acquired drug resistance, and avoiding side effects.
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Affiliation(s)
- M Sarkar
- Department of Pulmonary Medicine, Indira Gandhi Medical College, Shimla, 171001, Himachal Pradesh, India.
| | - J Sarkar
- MRes Neuroscience, University of Leeds, Leeds, UK
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Thoma Y, Cathignol AE, Pétermann YJ, Sariko ML, Said B, Csajka C, Guidi M, Mpagama SG. Toward a Clinical Decision Support System for Monitoring Therapeutic Antituberculosis Medical Drugs in Tanzania (Project TuberXpert): Protocol for an Algorithm' Development and Implementation. JMIR Res Protoc 2024; 13:e58720. [PMID: 39432902 PMCID: PMC11535787 DOI: 10.2196/58720] [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: 04/22/2024] [Revised: 07/12/2024] [Accepted: 07/20/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND The end tuberculosis (TB) strategy requires a novel patient treatment approach contrary to the one-size-fits-all model. It is well known that each patient's physiology is different and leads to various rates of drug elimination. Therapeutic drug monitoring (TDM) offers a way to manage drug dosage adaptation but requires trained pharmacologists, which is scarce in resource-limited settings. OBJECTIVE We will develop an automated clinical decision support system (CDSS) to help practitioners with the dosage adaptation of rifampicin, one of the essential medical drugs targeting TB, that is known for large pharmacokinetic variability and frequent suboptimal blood exposure. Such an advanced system will encourage the spread of a dosage-individualization culture, including among practitioners not specialized in pharmacology. Thus, the objectives of this project are to (1) develop the appropriate population pharmacokinetic (popPK) model for rifampicin for Tanzanian patients, (2) optimize the reporting of relevant information to practitioners for drug dosage adjustment, (3) automate the delivery of the report in line with the measurement of drug concentration, and (4) validate and implement the final system in the field. METHODS A total of 3 teams will combine their efforts to deliver the first automated TDM CDSS for TB. A cross-sectional study will be conducted to define the best way to display information to clinicians. In parallel, a rifampicin popPK model will be developed taking advantage of the published literature, complemented with data provided by existing literature data from the Pan-African Consortium for the Evaluation of Antituberculosis Antibiotics (panACEA), and samples collected within this project. A decision tree will be designed and implemented as a CDSS, and an automated report generation will be developed and validated through selected case studies. Expert pharmacologists will validate the CDSS, and finally, field implementation in Tanzania will occur, coupled with a prospective study to assess clinicians' adherence to the CDSS recommendations. RESULTS The TuberXpert project started in November 2022. In July 2024, the clinical study in Tanzania was completed with the enrollment of 50 patients to gather the required data to build a popPK model for rifampicin, together with a qualitative study defining the report design, as well as the CDSS general architecture definition. CONCLUSIONS At the end of the TuberXpert project, Tanzania will possess a new tool to help the practitioners with the adaptation of drug dosage targeting complicated TB cases (TB or HIV, TB or diabetes mellitus, and TB or malnutrition). This automated system will be validated and used in the field and will be proposed to other countries affected by endemic TB. In addition, this approach will serve as proof of concept regarding the feasibility and suitability of CDSS-assisted TDM for further anti-TB drugs in TB-burdened areas deprived of TDM experts, including second-line treatments considered important to monitor. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/58720.
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Affiliation(s)
- Yann Thoma
- School of Engineering and Management Vaud, HES-SO University of Applied Sciences and Arts Western Switzerland, Yverdon-les-Bains, Switzerland
| | - Annie E Cathignol
- School of Engineering and Management Vaud, HES-SO University of Applied Sciences and Arts Western Switzerland, Yverdon-les-Bains, Switzerland
- Centre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Yuan J Pétermann
- Centre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | | | - Bibie Said
- Kibong'oto Infectious Diseases Hospital, Sanya Juu, United Republic of Tanzania
- The Nelson Mandela African Institution of Science and Technology, Arusha, United Republic of Tanzania
| | - Chantal Csajka
- Centre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland
- School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
| | - Monia Guidi
- Centre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland
- Service of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Stellah G Mpagama
- Kibong'oto Infectious Diseases Hospital, Sanya Juu, United Republic of Tanzania
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Wang Y, Shi J, Yin X, Tao B, Shi X, Mao X, Wen Q, Xue Y, Wang J. The impact of diabetes mellitus on tuberculosis recurrence in Eastern China: a retrospective cohort study. BMC Public Health 2024; 24:2534. [PMID: 39294658 PMCID: PMC11409766 DOI: 10.1186/s12889-024-20019-5] [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: 08/06/2024] [Accepted: 09/09/2024] [Indexed: 09/21/2024] Open
Abstract
BACKGROUND The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a significant global public health issue. This study aims to explore the recurrence risk and related factors of active pulmonary TB, specifically focusing on the impact of DM. METHODS A retrospective cohort study was conducted in Lianyungang City, Jiangsu Province, Eastern China by recruiting 12,509 individuals with newly diagnosed pulmonary TB between 2011 and 2019. The Cox proportional hazards models were performed to identify risk factors of recurrence and assess the association between DM and recurrence. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS After a median follow-up period of 5.46 years, we observed 439 recurrent cases (incident recurrence rate: 6.62 per 1000 person-years). Males (HR: 1.30, 95% CI: 1.03-1.64), patients aged ≥ 60 years (HR: 1.39, 95% CI: 1.15-1.70), DM (HR: 2.40, 95% CI: 1.68-3.45), and etiologic positivity in the initial episode (HR: 2.42, 95% CI: 2.00-2.92) had a significantly increased risk of recurrence. CONCLUSIONS Recurrence of pulmonary TB patients who have completed treatment, especially those who also suffer from DM, should be a concern. Enhanced follow-up and targeted surveillance of these high-risk groups are needed.
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Affiliation(s)
- Yuting Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, China
| | - Jinyan Shi
- Department of Clinical Laboratory, The Fourth People's Hospital of Lianyungang, Lianyungang, 222000, China
| | - Xiwen Yin
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, China
| | - Bilin Tao
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, China
| | - Xinling Shi
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, China
| | - Xinlan Mao
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, China
| | - Qin Wen
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, China
| | - Yuan Xue
- Department of Infectious Diseases, The Third People's Hospital of Changzhou, Changzhou Medical Center, Nanjing Medical University, 300 Lanling North Road, Changzhou, 213001, China.
| | - Jianming Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, China.
- Department of Infectious Diseases, The Third People's Hospital of Changzhou, Changzhou Medical Center, Nanjing Medical University, 300 Lanling North Road, Changzhou, 213001, China.
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Al-Bari MAA, Peake N, Eid N. Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges. World J Diabetes 2024; 15:853-866. [PMID: 38766427 PMCID: PMC11099355 DOI: 10.4239/wjd.v15.i5.853] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/08/2024] [Accepted: 03/21/2024] [Indexed: 05/10/2024] Open
Abstract
Tuberculosis (TB) remains a leading cause of death among infectious diseases, particularly in poor countries. Viral infections, multidrug-resistant and ex-tensively drug-resistant TB strains, as well as the coexistence of chronic illnesses such as diabetes mellitus (DM) greatly aggravate TB morbidity and mortality. DM [particularly type 2 DM (T2DM)] and TB have converged making their control even more challenging. Two contemporary global epidemics, TB-DM behaves like a syndemic, a synergistic confluence of two highly prevalent diseases. T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment. Since a bidirectional relationship exists between TB and DM, it is necessary to concurrently treat both, and promote recommendations for the joint management of both diseases. There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure, and reinfection. In addition, autophagy may play a role in these comorbidities. Therefore, the TB-DM comorbidities present several health challenges, requiring a focus on multidisciplinary collaboration and integrated strategies, to effectively deal with this double burden. To effectively manage the comorbidity, further screening in affected countries, more suitable drugs, and better treatment strategies are required.
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Affiliation(s)
| | - Nicholas Peake
- Biosciences and Chemistry and Biomolecular Research Centre, Sheffield Hallam University, Sheffield S1 1WB, United Kingdom
| | - Nabil Eid
- Department of Anatomy, Division of Human Biology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
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Chen RH, Michael T, Kuhlin J, Schön T, Stocker S, Alffenaar JWC. Is there a need to optimise pyrazinamide doses in patients with tuberculosis? A systematic review. Int J Antimicrob Agents 2023; 62:106914. [PMID: 37419292 DOI: 10.1016/j.ijantimicag.2023.106914] [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: 01/30/2023] [Revised: 06/09/2023] [Accepted: 06/30/2023] [Indexed: 07/09/2023]
Abstract
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log10 CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
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Affiliation(s)
- Ricky Hao Chen
- School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Toni Michael
- School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Johanna Kuhlin
- Karolinska Institutet, Department of Medicine Solna, Division of Infectious Diseases, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Thomas Schön
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden; Department of Infectious Diseases, Kalmar County Hospital, Linköping University, Kalmar, Sweden
| | - Sophie Stocker
- School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, NSW, Australia; School of Clinical Medicine, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, The University of New South Wales, Sydney, NSW, Australia; Sydney Institute for Infectious Diseases, University of Sydney, Sydney, NSW, Australia
| | - Jan-Willem C Alffenaar
- School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Westmead Hospital, Sydney, NSW, Australia; Sydney Institute for Infectious Diseases, University of Sydney, Sydney, NSW, Australia.
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Konkor I, Kuuire VZ. Epidemiologic transition and the double burden of disease in Ghana: What do we know at the neighborhood level? PLoS One 2023; 18:e0281639. [PMID: 36827236 PMCID: PMC9956066 DOI: 10.1371/journal.pone.0281639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 01/27/2023] [Indexed: 02/25/2023] Open
Abstract
Many developing countries including Ghana are currently experiencing dual disease burdens emerging from an unprecedented risk overlap that drive their epidemiological transitions. Yet, siloed and disintegrated approaches continue to take precedence in health research and policy programs that drive competition for limited resources to address competing health problems. The objective of this study was to offer empirical evidence in support of a cogent argument for an integrated framework for the study and management of infectious and chronic health conditions in Ghana. We did so by examining the prevalence, determinants, and neighborhoods trajectories of the double burden of disease using data from a cross-sectional neighborhood-based study in Ghana. We fitted multinomial multilevel multivariate models to a sample of 1377 individual surveys and the results presented as odds ratios. Findings show that amidst a rising burden of NCDs, infectious diseases remain the most common health condition and participants in deprived neighborhoods were significantly more likely to report poor health outcomes. Risk factors such as tobacco and alcohol consumption were significantly associated with NCDs and infectious diseases and respondents who reported being diagnosed with NCDs and infectious diseases in the past year were likely to engage in leisure time physical activities and eat healthy. Based on our findings, we recommend health reforms in Ghana and argue for the design and implementation of an integrated framework for the study and management of the double burden of disease in Ghana and similar developing country settings.
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Affiliation(s)
- Irenius Konkor
- Department of Geography, Geomatics and Environment, University of Toronto Mississauga, Mississauga, Canada
- * E-mail:
| | - Vincent Z. Kuuire
- Department of Geography, Geomatics and Environment, University of Toronto Mississauga, Mississauga, Canada
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Zhang H, He Y, Davies Forsman L, Paues J, Werngren J, Niward K, Schön T, Bruchfeld J, Alffenaar JW, Hu Y. Population pharmacokinetics and dose evaluations of linezolid in the treatment of multidrug-resistant tuberculosis. Front Pharmacol 2023; 13:1032674. [PMID: 36699070 PMCID: PMC9868619 DOI: 10.3389/fphar.2022.1032674] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 12/15/2022] [Indexed: 01/11/2023] Open
Abstract
Background: The pharmacokinetic/pharmacodynamics (PK/PD) target derived from the hollow-fiber system model for linezolid for treatment of the multidrug-resistant tuberculosis (MDR-TB) requires clinical validation. Therefore, this study aimed to develop a population PK model for linezolid when administered as part of a standardized treatment regimen, to identify the PK/PD threshold associated with successful treatment outcomes and to evaluate currently recommended linezolid doses. Method: This prospective multi-center cohort study of participants with laboratory-confirmed MDR-TB was conducted in five TB designated hospitals. The population PK model for linezolid was built using nonlinear mixed-effects modeling using data from 168 participants. Boosted classification and regression tree analyses (CART) were used to identify the ratio of 0- to 24-h area under the concentration-time curve (AUC0-24h) to the minimal inhibitory concentration (MIC) threshold using the BACTEC MGIT 960 method associated with successful treatment outcome and validated in multivariate analysis using data from a different and prospective cohort of 159 participants with MDR-TB. Furthermore, based on the identified thresholds, the recommended doses were evaluated by the probability of target attainment (PTA) analysis. Result: Linezolid plasma concentrations (1008 samples) from 168 subjects treated with linezolid, were best described by a 2-compartment model with first-order absorption and elimination. An AUC0-24h/MIC > 125 was identified as a threshold for successful treatment outcome. Median time to sputum culture conversion between the group with AUC0-24h/MIC above and below 125 was 2 versus 24 months; adjusted hazard ratio (aHR), 21.7; 95% confidence interval (CI), (6.4, 72.8). The boosted CART-derived threshold and its relevance to the final treatment outcome was comparable to the previously suggested target of AUC0-24h/MIC (119) using MGIT MICs in a hollow fiber infection model. Based on the threshold from the present study, at a standard linezolid dose of 600 mg daily, PTA was simulated to achieve 100% at MGIT MICs of ≤ .25 mg which included the majority (81.1%) of isolates in the study. Conclusion: We validated an AUC0-24h/MIC threshold which may serve as a target for dose adjustment to improve efficacy of linezolid in a bedaquiline-containing treatment. Linezolid exposures with the WHO-recommended dose (600 mg daily) was sufficient for all the M. tb isolates with MIC ≤ .25 mg/L.
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Affiliation(s)
- Haoyue Zhang
- Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, China
| | - Yuying He
- Institute of Tuberculosis Control, Guizhou Provincial Center for Disease Control and Prevention, Guiyang, China
| | - Lina Davies Forsman
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden,Department of Medicine, Division of Infectious Diseases, Karolinska Institute, Stockholm, Sweden
| | - Jakob Paues
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden,Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden
| | - Jim Werngren
- Department of Microbiology, The Public Health Agency of Sweden, Stockholm, Sweden
| | - Katarina Niward
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden,Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden
| | - Thomas Schön
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden,Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden,Department of Infectious Diseases, Kalmar County Hospital, Linköping University, Kalmar, Sweden
| | - Judith Bruchfeld
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden,Department of Medicine, Division of Infectious Diseases, Karolinska Institute, Stockholm, Sweden
| | - Jan-Willem Alffenaar
- University of Sydney, Faculty of Medicine and Health, School of Pharmacy, Sydney, NSW, Australia,Westmead Hospital, Sydney, NSW, Australia,Sydney Institute for Infectious Diseases, University of Sydney, Sydney, NSW, Australia
| | - Yi Hu
- Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, China,*Correspondence: Yi Hu,
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Wang Y, Zhou Y, Chen L, Cheng Y, Lai H, Lyu M, Zeng J, Zhang Y, Feng P, Ying B. Metformin promotes smear conversion in tuberculosis‐diabetes comorbidity and construction of prediction models. J Clin Lab Anal 2022; 36:e24755. [DOI: 10.1002/jcla.24755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 10/15/2022] [Accepted: 10/17/2022] [Indexed: 11/11/2022] Open
Affiliation(s)
- Yili Wang
- West China Hospital Sichuan University Chengdu China
- West China School of Medicine Sichuan University Chengdu China
| | - Yanbing Zhou
- West China Hospital Sichuan University Chengdu China
- West China School of Medicine Sichuan University Chengdu China
| | - Liyu Chen
- Center for Infectious Diseases West China Hospital, Sichuan University Chengdu China
| | - Yuhui Cheng
- West China Hospital Sichuan University Chengdu China
- West China School of Medicine Sichuan University Chengdu China
| | - Hongli Lai
- West China Hospital Sichuan University Chengdu China
- West China School of Medicine Sichuan University Chengdu China
| | - Mengyuan Lyu
- West China Hospital Sichuan University Chengdu China
- West China School of Medicine Sichuan University Chengdu China
| | | | - Yao Zhang
- Ganzi People’s Hospital Ganzi Prefecture China
| | - Ping Feng
- Center for Infectious Diseases West China Hospital, Sichuan University Chengdu China
| | - Binwu Ying
- West China Hospital Sichuan University Chengdu China
- West China School of Medicine Sichuan University Chengdu China
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Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models. Eur J Clin Pharmacol 2022; 78:1535-1553. [PMID: 35852584 PMCID: PMC9482569 DOI: 10.1007/s00228-022-03362-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/29/2022] [Indexed: 11/19/2022]
Abstract
Purpose Significant pharmacokinetic variabilities have been reported for isoniazid across various populations. We aimed to summarize population pharmacokinetic studies of isoniazid in tuberculosis (TB) patients with a specific focus on the influence of N-acetyltransferase 2 (NAT2) genotype/single-nucleotide polymorphism (SNP) on clearance of isoniazid. Methods A systematic search was conducted in PubMed and Embase for articles published in the English language from inception till February 2022 to identify population pharmacokinetic (PopPK) studies of isoniazid. Studies were included if patient population had TB and received isoniazid therapy, non-linear mixed effects modelling, and parametric approach was used for building isoniazid PopPK model and NAT2 genotype/SNP was tested as a covariate for model development. Results A total of 12 articles were identified from PubMed, Embase, and hand searching of articles. Isoniazid disposition was described using a two-compartment model with first-order absorption and linear elimination in most of the studies. Significant covariates influencing the pharmacokinetics of isoniazid were NAT2 genotype, body weight, lean body weight, body mass index, fat-free mass, efavirenz, formulation, CD4 cell count, and gender. Majority of studies conducted in adult TB population have reported a twofold or threefold increase in isoniazid clearance for NAT2 rapid acetylators compared to slow acetylators. Conclusion The variability in disposition of isoniazid can be majorly attributed to NAT2 genotype. This results in a trimodal clearance pattern with a multi-fold increase in clearance of NAT2 rapid acetylators compared to slow acetylators. Further studies exploring the generalizability/adaptability of developed PopPK models in different clinical settings are required.
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Sileshi T, Mekonen G, Makonnen E, Aklillu E. Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review. Pharmgenomics Pers Med 2022; 15:561-571. [PMID: 35693129 PMCID: PMC9176238 DOI: 10.2147/pgpm.s363058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 05/23/2022] [Indexed: 11/23/2022] Open
Abstract
Background Rifamycins are a novel class of antibiotics clinically approved for tuberculosis chemotherapy. They are characterized by high inter-individual variation in pharmacokinetics. This systematic review aims to present the contribution of genetic variations in drug-metabolizing enzymes and transporter proteins to the inter-individual variation of rifamycin pharmacokinetics. Method We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The search for relevant studies was done through PubMed, Embase, Web of Science, and Scopus databases. Studies reporting single nucleotide polymorphism in drug transporters and metabolizing enzymes' influence on rifamycin pharmacokinetics were solely included. Two reviewers independently performed data extraction. Results The search identified 117 articles of which 15 fulfilled the eligibility criteria and were included in the final data synthesis. The single nucleotides polymorphism in the drug transporters SLCO1B1 rs4149032, rs2306283, rs11045819, and ABCB1 rs1045642 for rifampicin, drug metabolizing enzyme AADAC rs1803155 for rifapentine and CES2 c.-22263A>G (g.738A>G) for rifampicin partly contributes to the variability of pharmacokinetic parameters in tuberculosis patients. Conclusion The pharmacokinetics of rifamycins is influenced by genetic variation of drug-metabolizing enzymes and transporters. Controlled clinical studies are, however, required to establish these relationships.
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Affiliation(s)
- Tesemma Sileshi
- Department of Pharmacy, Ambo University, Ambo, Ethiopia
- Department of Pharmacology and Clinical Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Eyasu Makonnen
- Department of Pharmacology and Clinical Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia
- Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia
| | - Eleni Aklillu
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
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12
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Alffenaar JWC, Stocker SL, Forsman LD, Garcia-Prats A, Heysell SK, Aarnoutse RE, Akkerman OW, Aleksa A, van Altena R, de Oñata WA, Bhavani PK, Van't Boveneind-Vrubleuskaya N, Carvalho ACC, Centis R, Chakaya JM, Cirillo DM, Cho JG, D Ambrosio L, Dalcolmo MP, Denti P, Dheda K, Fox GJ, Hesseling AC, Kim HY, Köser CU, Marais BJ, Margineanu I, Märtson AG, Torrico MM, Nataprawira HM, Ong CWM, Otto-Knapp R, Peloquin CA, Silva DR, Ruslami R, Santoso P, Savic RM, Singla R, Svensson EM, Skrahina A, van Soolingen D, Srivastava S, Tadolini M, Tiberi S, Thomas TA, Udwadia ZF, Vu DH, Zhang W, Mpagama SG, Schön T, Migliori GB. Clinical standards for the dosing and management of TB drugs. Int J Tuberc Lung Dis 2022; 26:483-499. [PMID: 35650702 PMCID: PMC9165737 DOI: 10.5588/ijtld.22.0188] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 04/04/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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Affiliation(s)
- J W C Alffenaar
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia
| | - S L Stocker
- School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Department of Clinical Pharmacology and Toxicology, St Vincent´s Hospital, Sydney, NSW, Australia, St Vincent´s Clinical Campus, University of NSW, Kensington, NSW, Australia
| | - L Davies Forsman
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Solna, Sweden, Department of Infectious Diseases Karolinska University Hospital, Solna, Sweden
| | - A Garcia-Prats
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa, Department of Pediatrics, University of Wisconsin, Madison, WI
| | - S K Heysell
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA
| | - R E Aarnoutse
- Department of Pharmacy, Radboud Institute for Health Sciences & Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - O W Akkerman
- University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands, University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands
| | - A Aleksa
- Educational Institution "Grodno State Medical University", Grodno, Belarus
| | - R van Altena
- Asian Harm Reduction Network (AHRN) and Medical Action Myanmar (MAM) in Yangon, Myanmar
| | - W Arrazola de Oñata
- Belgian Scientific Institute for Public Health (Belgian Lung and Tuberculosis Association), Brussels, Belgium
| | - P K Bhavani
- Indian Council of Medical Research-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai, India
| | - N Van't Boveneind-Vrubleuskaya
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, Department of Public Health TB Control, Metropolitan Public Health Services, The Hague, The Netherlands
| | - A C C Carvalho
- Laboratório de Inovações em Terapias, Ensino e Bioprodutos (LITEB), Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - R Centis
- Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Tradate, Italy
| | - J M Chakaya
- Department of Medicine, Therapeutics and Dermatology, Kenyatta University, Nairobi, Kenya, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - D M Cirillo
- Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - J G Cho
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia, Parramatta Chest Clinic, Parramatta, NSW, Australia
| | - L D Ambrosio
- Public Health Consulting Group, Lugano, Switzerland
| | - M P Dalcolmo
- Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
| | - P Denti
- Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - K Dheda
- Centre for Lung Infection and Immunity, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Cape Town, South Africa, University of Cape Town Lung Institute & South African MRC Centre for the Study of Antimicrobial Resistance, Cape Town, South Africa, Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK
| | - G J Fox
- Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia, Woolcock Institute of Medical Research, Glebe, NSW, Australia
| | - A C Hesseling
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa
| | - H Y Kim
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia
| | - C U Köser
- Department of Genetics, University of Cambridge, Cambridge, UK
| | - B J Marais
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, Department of Infectious Diseases and Microbiology, The Children´s Hospital at Westmead, Westmead, NSW, Australia
| | - I Margineanu
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - A G Märtson
- Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - M Munoz Torrico
- Clínica de Tuberculosis, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, Mexico
| | - H M Nataprawira
- Division of Paediatric Respirology, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung, Indonesia
| | - C W M Ong
- Infectious Disease Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Institute for Health Innovation & Technology (iHealthtech), National University of Singapore, Singapore, Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore
| | - R Otto-Knapp
- German Central Committee against Tuberculosis (DZK), Berlin, Germany
| | - C A Peloquin
- Infectious Disease Pharmacokinetics Laboratory, Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA
| | - D R Silva
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - R Ruslami
- TB/HIV Research Centre, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia, Department of Biomedical Sciences, Division of Pharmacology and Therapy, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - P Santoso
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, Indonesia
| | - R M Savic
- Department of Bioengineering and Therapeutic Sciences, Division of Pulmonary and Critical Care Medicine, Schools of Pharmacy and Medicine, University of California San Francisco, San Francisco, CA, USA
| | - R Singla
- Department of TB & Respiratory Diseases, National Institute of TB & Respiratory Diseases, New Delhi, India
| | - E M Svensson
- Department of Pharmacy, Radboud Institute for Health Sciences & Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands, Department of Pharmacy, Uppsala University, Uppsala, Sweden
| | - A Skrahina
- The Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus
| | - D van Soolingen
- National Institute for Public Health and the Environment, TB Reference Laboratory (RIVM), Bilthoven, The Netherlands
| | - S Srivastava
- Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA
| | - M Tadolini
- Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - S Tiberi
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - T A Thomas
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA
| | - Z F Udwadia
- P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
| | - D H Vu
- National Drug Information and Adverse Drug Reaction Monitoring Centre, Hanoi University of Pharmacy, Hanoi, Vietnam
| | - W Zhang
- Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People´s Republic of China
| | - S G Mpagama
- Kilimanjaro Christian Medical University College, Moshi, United Republic of Tanzania, Kibong´oto Infectious Diseases Hospital, Sanya Juu, Siha, Kilimanjaro, United Republic of Tanzania
| | - T Schön
- Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden, Institute of Biomedical and Clinical Sciences, Division of Infection and Inflammation, Linköping University, Linköping, Sweden, Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Linköping University, Linköping, Sweden
| | - G B Migliori
- Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Tradate, Italy
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13
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Impact of diabetes mellitus on rifampicin's plasma concentration and bioavailability in patients with tuberculosis: A systematic review and meta-analysis study. Therapie 2022; 78:313-324. [DOI: 10.1016/j.therap.2022.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/27/2022] [Accepted: 05/16/2022] [Indexed: 11/19/2022]
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Metwally AS, El-Sheikh SMA, Galal AAA. The impact of diabetes mellitus on the pharmacokinetics of rifampicin among tuberculosis patients: A systematic review and meta-analysis study. Diabetes Metab Syndr 2022; 16:102410. [PMID: 35144181 DOI: 10.1016/j.dsx.2022.102410] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 01/15/2022] [Accepted: 01/18/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND AND AIMS Diabetes mellitus has a negative impact on the treatment outcome of tuberculosis, increasing the incidence of treatment failure and relapse. There is a scarcity of knowledge concerning the impact of diabetes mellitus on the pharmacokinetics of rifampicin. This study was conducted to evaluate the impact of diabetes mellitus on the pharmacokinetics of rifampicin among patients with tuberculosis. METHODS We explored the Web of Science, Cochrane Library, PubMed, and Scopus databases for articles that reported the pharmacokinetic parameters of rifampicin in diabetic and nondiabetic patients with tuberculosis published until September 2020. Based on the presence or absence of heterogeneity, pooled estimates were calculated using a random or fixed effect model. RESULTS Seven studies were relevant and included in this study. The Tmax of rifampicin increased in diabetic patients with tuberculosis compared with nondiabetic patients with tuberculosis (MD 0.84, 95% CI (0.32, 1.35), p = 0.002). No significant differences were detected in rifampicin Cmax (MD 0.18, 95% CI (-0.52, 0.88), p = 0.61), AUC0-24 (SMD -0.02, 95% CI (-0.34, 0.30), p = 0.90), Vd (MD -3.89, 95% CI (-11.17, 3.38), p = 0.29), CL (MD -0.13, 95%CI (-0.88, 0.61), p = 0.72), and MRT (MD 1.89, 95% CI (-0.03, 3.81), p = 0.05) between diabetic and nondiabetic patients with tuberculosis. CONCLUSION Diabetes mellitus increased the Tmax of rifampicin without further impact on other rifampicin pharmacokinetic parameters such as Cmax, AUC0-24, Vd, CL and MRT. Early therapeutic drug monitoring of rifampicin is necessary for diabetic tuberculosis patients.
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Affiliation(s)
- Amera Sh Metwally
- Zagazig University Hospitals, Zagazig University, 44519, Zagazig, Egypt.
| | - Sawsan M A El-Sheikh
- Professor of Pharmacology, Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt
| | - Azza A A Galal
- Professor of Pharmacology, Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt
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15
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Cáceres G, Calderon R, Ugarte-Gil C. Tuberculosis and comorbidities: treatment challenges in patients with comorbid diabetes mellitus and depression. Ther Adv Infect Dis 2022; 9:20499361221095831. [PMID: 35646347 PMCID: PMC9130847 DOI: 10.1177/20499361221095831] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 04/03/2022] [Indexed: 11/23/2022] Open
Abstract
Tuberculosis is one of the leading causes of death worldwide, primarily affecting
low- and middle income countries and individuals with limited-resources within
fractured health care systems. Unfortunately, the COVID-19 pandemic has only
served to aggravate the already existing diagnostic gap, decreasing the number
of people who get diagnosed and thereby complete successful treatment. In
addition to this, comorbidities act as an external component that when added to
the TB management equation, renders it even more complex. Among the various
comorbidities that interact with TB disease, diabetes mellitus and depression
are two of the most prevalent among non-communicable diseases within the TB
population and merits a thoughtful consideration when the healthcare system
provides care for them. TB patients with diabetes mellitus (TB-DM) or depression
both have an increased risk of mortality, relapse and recurrence. Both of these
diseases when in presence of TB present a ‘vicious-circle-like’ mechanism,
meaning that the effect of each disease can negatively add up, in a synergistic
manner, complicating the patient’s health state. Among TB-DM patients, high
glucose blood levels can decrease the effectiveness of anti-tuberculosis drugs;
however, higher doses of anti-tuberculous drugs could potentially decrease the
effects of DM drugs. Among the TB-depression patients, not only do we have the
adherence to treatment problems, but depression itself can biologically shift
the immunological profile responsible for TB containment, and the other way
around, TB itself can alter the hormonal balance of several neurotransmitters
responsible for depression. In this paper, we review these and other important
aspects such as the pharmacological interactions found in the treatment of TB-DM
and TB-depression patients and the implication on TB care and pharmacological
considerations.
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Affiliation(s)
- Guillermo Cáceres
- Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Rodrigo Calderon
- Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Cesar Ugarte-Gil
- Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430-San Martin de Porres, Lima, Perú
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16
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Ichikawa C, Tanaka S, Takubo M, Kushimoto M, Ikeda J, Ogawa K, Tsujino I, Suzuki Y, Abe M, Ishihara H, Fujishiro M. Tuberculosis Relapse in the Epididymis After the Completion of Nine Months of Anti-Tuberculosis Chemotherapy in a Patient with Poorly Controlled Diabetes Mellitus. Ther Clin Risk Manag 2021; 17:463-470. [PMID: 34079268 PMCID: PMC8164866 DOI: 10.2147/tcrm.s310463] [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: 03/10/2021] [Accepted: 05/09/2021] [Indexed: 11/25/2022] Open
Abstract
The standard six-month tuberculosis (TB) treatment comprises an intensive phase lasting two months, followed by a continuation phase lasting four months. Meanwhile, the nine-month regimen, which has a prolonged continuation phase, is indicated for patients with complicated diabetes mellitus (DM) because of their poor response to treatment. A 61-year-old Japanese man with poorly controlled DM for five years presented with bilateral scrotal swelling noticed two weeks ago. He had a history of pleuritis, pericarditis, and peritonitis two years ago. These symptoms led to the diagnosis of culture-negative extrapulmonary TB. He received the nine-month chemotherapy regimen (isoniazid, rifampin, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for seven months), and his symptoms significantly improved. The swollen scrotum was accompanied by mild tenderness and pus discharge from a fistula. Imaging study revealed bilaterally diffusely enlarged epididymis. However, the acid-fast bacilli smear and culture and polymerase chain reaction using urine and pus discharge tested negative. Bilateral epididymectomy was performed. Although the acid-fast bacilli smear was negative, the pathology demonstrated granuloma formation and acid-fast bacilli tissue culture confirmed multi-drug resistant Mycobacterium tuberculosis. The optimal treatment regimen and duration for extrapulmonary TB with unknown drug susceptibility are debatable. The nine-month regimen can be insufficient in some cases. Thus, detailed follow-up is essential, and TB relapse should be thoroughly monitored.
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Affiliation(s)
- Chikako Ichikawa
- Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Sho Tanaka
- Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.,Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan
| | - Masahiro Takubo
- Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.,Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan
| | - Masaru Kushimoto
- Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan
| | - Jin Ikeda
- Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan
| | - Katsuhiko Ogawa
- Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan.,Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Ichiro Tsujino
- Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan.,Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Yutaka Suzuki
- Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan.,Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Masanori Abe
- Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Hisamitsu Ishihara
- Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Midori Fujishiro
- Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.,Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan
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MANN SC, MORROW M, COYLE RP, COLEMAN SS, SADERUP A, ZHENG JH, ELLISON L, BUSHMAN LR, KISER JJ, MAWHINNEY S, ANDERSON PL, CASTILLO-MANCILLA JR. Lower Cumulative Antiretroviral Exposure in People Living With HIV and Diabetes Mellitus. J Acquir Immune Defic Syndr 2020; 85:483-488. [PMID: 33136749 PMCID: PMC7756101 DOI: 10.1097/qai.0000000000002460] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE People living with HIV (PLWH) are living longer and developing more non-AIDS comorbidities, which negatively impact antiretroviral therapy (ART) adherence. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a novel pharmacologic measure of cumulative ART adherence that is predictive of viral suppression and future viremia. However, the relationship between non-AIDS comorbidities and this adherence measure is unknown. We aimed to evaluate the association between 3 non-AIDS comorbidities (diabetes mellitus (DM), hypertension, and hyperlipidemia) and TFV-DP in DBS in PLWH. METHODS Blood for TFV-DP in DBS and HIV viral load was prospectively collected from PLWH on tenofovir disoproxil fumarate for up to 3 times over 48 weeks. Non-AIDS comorbidities were recorded. Mixed effect multivariable linear regression models were used to estimate the changes in TFV-DP concentrations in DBS according to the presence of comorbidities and to estimate the percent differences in TFV-DP concentrations between these groups. RESULTS A total of 1144 person-visits derived from 523 participants with available concentrations of TFV-DP in DBS were included in this analysis. In univariate analysis, no significant association between non-AIDS comorbidities (categorized as having 0, 1, 2, or 3 comorbidities) and the concentrations of TFV-DP in DBS was observed (P = 0.40). Participants who had DM had 25% lower (95% confidence interval: -36% to -12%; P < 0.001) TFV-DP in DBS than participants without DM after adjusting for age, gender, race, body mass index, estimated glomerular filtration rate, CD4 T-cell count, hematocrit, ART class, patient-level medication regimen complexity index, and 3-month self-reported adherence. CONCLUSIONS Diabetic PLWH have lower concentrations of TFV-DP in DBS compared with those without DM. Further research is required to identify the clinical implications and biological mechanisms underlying these findings.
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Affiliation(s)
- Sarah C. MANN
- Division of Infectious Diseases, School of Medicine, University of Colorado-AMC, Aurora, Colorado, United States
| | - Mary MORROW
- Department of Biostatistics and Bioinformatics, Colorado School of Public Health, Aurora, Colorado, United States
| | - Ryan P. COYLE
- Division of Infectious Diseases, School of Medicine, University of Colorado-AMC, Aurora, Colorado, United States
| | | | - Austin SADERUP
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-AMC, Aurora, Colorado, United States
| | - Jia-Hua ZHENG
- Colorado Antiviral Pharmacology Laboratory and Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-AMC, Aurora, Colorado, United States
| | - Lucas ELLISON
- Colorado Antiviral Pharmacology Laboratory and Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-AMC, Aurora, Colorado, United States
| | - Lane R. BUSHMAN
- Colorado Antiviral Pharmacology Laboratory and Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-AMC, Aurora, Colorado, United States
| | - Jennifer J. KISER
- Colorado Antiviral Pharmacology Laboratory and Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-AMC, Aurora, Colorado, United States
| | - Samantha MAWHINNEY
- Department of Biostatistics and Bioinformatics, Colorado School of Public Health, Aurora, Colorado, United States
| | - Peter L. ANDERSON
- Colorado Antiviral Pharmacology Laboratory and Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado-AMC, Aurora, Colorado, United States
| | - Jose R. CASTILLO-MANCILLA
- Division of Infectious Diseases, School of Medicine, University of Colorado-AMC, Aurora, Colorado, United States
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18
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Alffenaar JWC, Akkerman OW, Kim HY, Tiberi S, Migliori GB. Precision and personalized medicine and anti-TB treatment: Is TDM feasible for programmatic use? Int J Infect Dis 2020; 92S:S5-S9. [PMID: 31996324 DOI: 10.1016/j.ijid.2020.01.041] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 01/20/2020] [Accepted: 01/21/2020] [Indexed: 10/25/2022] Open
Abstract
Therapeutic Drug Monitoring (TDM) is increasingly recommended to ensure the correct drug dose thereby minimizing adverse events and maximizing regimen efficacy. To facilitate implementation in TB programs, a framework for TDM is urgently needed. TDM is only useful for dose optimization if a patient is on an appropriate regimen guided by drug susceptibility testing. TDM using a targeted approach selecting patients with risk factors for suboptimal drug exposure (e.g. diabetes) or not responding to treatment for drugs with a clear concentration-response relationship may provide the best value for money. Semiquantitative point-of-care tests for detection of low or high drug concentration should be implemented at community level while quantitative assays can be performed at regional or central level. Expanding PK/PD research followed by clinical trials including both clinical outcome as well as cost-effectiveness will increase the level of evidence supporting TDM.
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Affiliation(s)
- Jan-Willem C Alffenaar
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia; Westmead Hospital, Westmead, NSW 2145, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Camperdown, NSW 2006, Australia.
| | - Onno W Akkerman
- University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, TB Center Beatrixoord, Haren, The Netherlands
| | - Hannah Yejin Kim
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia; Westmead Hospital, Westmead, NSW 2145, Australia
| | - Simon Tiberi
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Department of Infection, Royal London and Newham Hospitals, Barts Health NHS Trust, London, United Kingdom
| | - Giovanni Battista Migliori
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy
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