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      Pulmonary Tuberculosis in Older Adults: Increased Mortality Related to Tuberculosis Within Two Months of Treatment Initiation

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          Abstract

          Background

          The proportion of tuberculosis (TB) patients who are older adults is increasing worldwide. Nearly 60% of TB patients in Japan are 70 years or older, and the TB incidence rate in Japan is one of the highest among high-income countries. The previous TB treatment guidelines prior to 2018 in Japan recommended excluding pyrazinamide (PZA) from the initial regimen for patients aged over 80 years.

          Objectives

          We aimed to examine differences in TB treatment outcomes among different age groups, and between those who received PZA and those who did not.

          Methods

          We performed a retrospective cohort study of patients with pulmonary TB who were managed at a single medical center in Japan. We compared treatment outcomes and adverse events that resulted in treatment interruption across the age groups.

          Results

          Of 246 patients, 117 (48%) were aged 75 years or older. Compared with patients aged < 74 years, those ≥ 75 years were less likely to have PZA in the initial regimen (53.0% vs 89.9%; < 0.0001), more likely to die during treatment (38.5% vs 6.2%; < 0.0001), and more likely to experience adverse events (30.8% vs 19.4%; < 0.05). The mortality rate related to TB at 2 months after TB treatment initiation was 28% in those aged ≥ 84 years. Furthermore, among patients aged ≥ 84 years, those who did not receive PZA were significantly more likely to die than those who did (65.8% vs 36.8%; < 0.05).

          Conclusions

          Patients aged ≥ 75 years with pulmonary TB experienced increased mortality related to TB during treatment and more frequent adverse events than younger patients, even though PZA was often avoided among older patients.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40266-021-00880-4.

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          Most cited references18

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          Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.

          The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.
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            Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020

            Summary Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221–47). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States. The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (e.g., with low-quality evidence). These updated 2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M. tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93–e142). The three rifamycin-based preferred regimens are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin-based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin-based regimens. In summary, short-course (3- to 4-month) rifamycin-based treatment regimens are preferred over longer-course (6–9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances.
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              Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults

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                Author and article information

                Contributors
                isanotaki@gmail.com
                Journal
                Drugs Aging
                Drugs Aging
                Drugs & Aging
                Springer International Publishing (Cham )
                1170-229X
                1179-1969
                5 July 2021
                : 1-9
                Affiliations
                [1 ]Department of Respiratory Medicine, National Hospital Organization Ibarakihigashi National Hospital, 825, Terunuma. Tokai-mura, Naka-gun, Ibaraki, 319-1113 Japan
                [2 ]Department of Pulmonary Medicine, Saitama City Hospital, Saitama, Japan
                [3 ]GRID grid.238801.0, ISNI 0000 0001 0435 8972, TB Control Program, Public Health-Seattle & King county, ; Seattle, WA USA
                [4 ]Department of Health Information Management, National Hospital Organization Ibarakihigashi National Hospital, Ibaraki, Japan
                [5 ]GRID grid.34477.33, ISNI 0000000122986657, Division of Pulmonary, Critical Care and Sleep Medicine, , University of Washington, ; Seattle, WA USA
                Author information
                http://orcid.org/0000-0003-3563-0136
                Article
                880
                10.1007/s40266-021-00880-4
                8256198
                34224105
                f0a8684c-a0f1-4101-afea-59cd0fecd676
                © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 13 June 2021
                Categories
                Original Research Article

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