Standard Tuberculosis Treatment Research Articles

Trends in the availability and prices of quality-assured tuberculosis drugs: a systematic analysis of Global Drug Facility Product Catalogs from 2001 to 2024

BackgroundThe Global Drug Facility (GDF) of the Stop TB Partnership was launched in 2001 with the goal of increasing access to quality-assured tuberculosis (TB) drugs and products. We aimed to describe the TB drugs and prices available from the GDF over time and to assess trends.MethodsWe searched the internet, including an internet archive, for past and recent GDF Product Catalogs and extracted the listed TB drugs and prices. We calculated the lowest price for the most common drug formulations assuming drugs with similar active pharmaceutical ingredients (APIs) are substitutes for each other. We assessed time trends in the TB drugs and prices offered by the GDF in univariable regressions over the longest possible period.ResultsWe identified 43 different GDF Product Catalogs published between November 2001 and May 2024. These product catalogs included 122 single medicines (31 APIs), 28 fixed-dose combinations (9 API combinations), and 8 patient kits (8 API regimens and other materials). The number of TB drugs listed in the GDF Product Catalog increased from 9 (8 APIs) to 55 (32 APIs). The price decreased for 17, increased for 19, and showed no trend for 12 APIs. The price of 15 (53.6%) of 28 APIs used against drug-resistant TB decreased, including the price of drugs used in new treatment regimens. The decreasing price trend was strongest for linezolid (-16.60 [95% CI: -26.35 to -6.85] percentage points [pp] per year), bedaquiline (-12.61 [95% CI: -18.00 to -7.22] pp per year), cycloserine (-11.20 [95% CI: -17.40 to -4.99] pp per year), pretomanid (-10.47 [95% CI: -15.06 to -5.89] pp per year), and rifapentine (-10.46 [95% CI: -12.86 to -8.06] pp per year). The prices of 16 (61.5%) of 23 APIs for standard drug-susceptible TB treatment increased, including rifampicin (23.70 [95% CI: 18.48 to 28.92] pp per year), isoniazid (20.95 [95% CI: 18.96 to 22.95] pp per year), ethambutol (9.85 [95% CI: 8.83 to 10.88] pp per year), and fixed-dose combinations thereof.ConclusionsThe number of TB drugs available from the GDF has substantially increased during its first 23 years of operation. The prices of most APIs for new TB treatments decreased or remained stable. The prices of most APIs for standard drug-sensitive TB treatment increased.

Fecal microbiota transplantation: A potential novel treatment strategy for extensively drug-resistant tuberculosis

Tuberculosis (TB) is one of the infectious diseases with the highest mortality and morbidity. The evolution of drug-resistant TB, particularly extensively drug-resistant TB (XDR-TB) is a global concern. The current anti-TB treatment regimens for XDR-TB are long and associated with adverse events, low patient adherence, and low success rates. Fecal microbiota transplantation (FMT) was approved for the treatment of recurrent or refractory Clostridium difficile infection in 2019 and has been shown to be a safe and well-tolerated treatment strategy. Given the bidirectional movement and interaction of metabolites, hormones, and cytokines between the gut and the lungs, FMT may be able to enhance overall XDR-TB treatment by facilitating immune cell activation. Here, we hypothesize that FMT, in conjunction with standard TB treatment, may improve TB treatment outcomes for those with XDR-TB. We discuss the efficacy, safety, and ethical issues associated with the use of FMT.

Safety of pyrazinamide in elderly patients with tuberculosis in Japan: A nationwide cohort study.

Pyrazinamide (PZA) is the standard first-line treatment for tuberculosis (TB); however, its safety in elderly patients has not been thoroughly investigated. This retrospective study used data from the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for TB between July 2010 and March 2022. Patients were categorized into HRE (isoniazid, rifampicin and ethambutol) and HREZ (isoniazid, rifampicin, ethambutol and PZA) groups. Primary outcomes included in-hospital mortality and overall adverse events (characterized by a composite of hepatotoxicity, gout attack, allergic reactions and gastrointestinal intolerance). Secondary outcomes included the length of hospital stay, 90-day readmission and use of drugs related to the primary outcome adverse events. Data were analysed using propensity score matching; we also conducted a subgroup analysis for those aged ≥75 years. Among 19,930 eligible patients, 8924 received HRE and 11,006 received HREZ. Propensity score matching created 3578 matched pairs with a mean age of approximately 80 years. Compared with the HRE group, the HREZ group demonstrated a higher proportion of overall adverse events (3.1% vs. 4.7%; p < 0.001), allergic reactions (1.4% vs. 2.5%; p < 0.001) and antihistamine use (21.9% vs. 27.6%; p < 0.001). No significant differences were observed regarding in-hospital mortality, hepatotoxicity or length of hospital stay between the groups. Subgroup analysis for those aged ≥75 years showed consistent results. Medical practitioners may consider adding PZA to an initial treatment regimen even in elderly patients with TB.

Tuberculous Spondylodiscitis with Psoas Abscess Descending into the Anterior Femoral Compartment Identified Using 2-deoxy-2-[18F]fluoroglucose Positron Emission Tomography Computed Tomography.

A 24-year-old immunocompetent woman underwent whole-body 18F-FDG PET/CT for the evaluation of MRI-suspicious tuberculous spinal lesions. The PET/CT results showed no pathological uptake in either lung, and there were no pathological changes on CT. There was increased uptake in the right psoas muscle, extending continuously down anterior to the right hip joint, posterior to and around the trochanteric region of the right femur, and into the right thigh, with an SUVmaxbw of 17.0. Subsequently, the patient underwent CT-guided biopsy as per protocol, which revealed drug-sensitive Mycobacterium tuberculosis, and the patient was started on standard tuberculosis treatment for 12 months.

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial

BackgroundHIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB.MethodsThis is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events.DiscussionDisseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice.Trial registrationClinicalTrials.gov NCT04951986. Registered on 7 July 2021https://clinicaltrials.gov/study/NCT04951986

Experience With Four-Month Rifapentine and Moxifloxacin-Based Tuberculosis Treatment in San Francisco.

A multicountry randomized controlled trial has demonstrated that pan-susceptible pulmonary tuberculosis (TB) can be successfully treated with a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide (HPMZ). We piloted HPMZ in San Francisco (SF) using a modified version of the US Centers for Disease Control and Prevention HPMZ treatment guidelines. In this retrospective cohort, patients consecutively referred to SF TB clinic were evaluated for HPMZ eligibility based on preestablished inclusion/exclusion criteria. All underwent evaluation and management according to national recommendations. We reviewed the medical records of those initiated on HPMZ. From August 2021 to December 2023, 30 (18.8%) of 160 patients diagnosed with active TB met HPMZ inclusion criteria; of these, 22 (13.8%) started HPMZ. The median age (range) was 32.5 (14-86) years, 17 (77.3%) were otherwise healthy, and 19 (86.4%) had pulmonary TB, including 7 (36.8%) with cavitary disease. Eighteen (81.8%) patients had an adverse event, with 11 (50%) prematurely discontinuing HPMZ; the most common adverse events were vomiting, elevated transaminases, and rash. To date, 9 (40.9%) have completed treatment, with most achieving criteria for cure. One patient was diagnosed with possible TB recurrence and restarted standard TB treatment. Our experience, with half of patients to date prematurely discontinuing HPMZ, illustrates the challenge of extrapolating findings from TB clinical trials commonly conducted in high-incidence, non-US settings to US clinical practice. Further experience may help identify best practices for implementing HPMZ, including identifying predictors of which patients may be most likely to benefit from and tolerate this regimen.

Adjunctive pascolizumab in rifampicin-susceptible pulmonary tuberculosis: proof-of-concept, partially-randomised, double-blind, placebo-controlled, dose-escalation trial.

Interleukin-4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanised anti-IL-4 monoclonal antibody) as adjunctive tuberculosis treatment. Participants with rifampicin-susceptible pulmonary tuberculosis received a single intravenous infusion of pascolizumab or placebo; and standard 6-month tuberculosis treatment. Pascolizumab dose increased in successive cohorts: [1] non-randomised 0.05 mg/kg (n = 4); [2] non-randomised 0.5 mg/kg (n = 4); [3] randomised 2.5 mg/kg (n = 9) or placebo (n = 3); [4] randomised 10 mg/kg (n = 9) or placebo (n = 3). Co-primary safety outcome was study-drug-related grade 4 or serious adverse event (G4/SAE); in all cohorts (1-4). Co-primary efficacy outcome was week-8 sputum culture time-to-positivity (TTP); in randomised cohorts (3-4) combined. Pascolizumab levels exceeded IL-4 50% neutralising dose for 8 weeks in 78-100% of participants in cohorts 3-4. There were no study-drug-related G4/SAEs. Median week-8 TTP was 42 days in pascolizumab and placebo groups (p = 0.185). Rate of TTP increase was greater with pascolizumab (difference from placebo 0.011 [95% Bayesian credible interval 0.006 to 0.015] log10TTP/day. There was no evidence to suggest blocking IL-4 was unsafe. Preliminary efficacy findings are consistent with animal models. This supports further investigation of adjunctive anti-IL-4 interventions for tuberculosis in larger phase 2 trials.

Evaluation of Systemic Inflammation Before and After Standard Anti-tuberculosis Treatment in Patients With Active Pulmonary Tuberculosis and Diabetes Mellitus.

Background Diabetes mellitus (DM) is a common comorbidity of active pulmonary tuberculosis (APTB) that increases the risk of treatment failure during anti-tuberculosis chemotherapy. Evaluating systemic inflammatory response could help determine differences in response to treatment between APTB patients and those with APTB and DM. Methodology To explore changes in systemic inflammation, measured by a set of inflammatory mediators in subjects with APTB and TBDM before and after six months of anti-tuberculosis chemotherapy, 30 APTB and nine TBDM subjects underwent cytokine testing, including interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta 1 (TGF-β1) by enzyme-linked immunosorbent assay, C-reactive protein by nephelometry, and sialic acid by colorimetric assay at baseline and following six months of standard anti-tuberculosis treatment. Sputum smear microscopy or molecular biology (Xpert MTB/RIF) was used for diagnosis, and sputum smear microscopy was performed monthly during the treatment of the patient with pulmonary tuberculosis to evaluate his evolution. Principal component analysis examined changes in the inflammatory status. Results Both groups showed negative sputum smear microscopy in the sixth month after starting anti-tuberculosis chemotherapy. TGF-β1 was found to be significantly higher in subjects with TBDM before treatment compared to APTB patients (p<0.001), and systemic inflammation continued only in TBDM subjects after treatment (accumulation and persistence of inflammatory mediators like IL-6, IL-8, IL-10, IFN-γ, TNF-α, TGF-β1, C-reactive protein, and sialic acid in blood). On the other hand, the mediators IFN-γ, C-reactive protein, and total sialic acid were found to be most influential in distinguishing pre- and post-treatment inflammatory response in subjects with APTB without DM. Conclusions Inflammatory mediators analyzed in combination, including IFN-γ, CRP, and total sialic acid, may be useful in evaluating the systemic inflammatory response in subjects with APTB and TBDM before and after anti-tuberculosis treatment. Determining these mediators revealed persistent systemic inflammation in TBDM subjects after six months of standard tuberculosis treatment, despite negative sputum smear microscopy results and good glycemic control. This suggests a need for inflammation-modulating therapies during tuberculosis control. Finally, monitoring sputum smear microscopy results alongside the determination of proposed inflammatory mediators (IFN-γ, CRP, and total sialic acid) are effective in evaluating the response to anti-tuberculosis treatment in APTB subjects without DM, warranting further investigation.

Pharmacokinetics of antitubercular drugs in patients hospitalized with HIV-associated tuberculosis: a population modeling analysis.

Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups. Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM ® was used to analyze the data. Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin's absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid's clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide's clearance was more variable among hospitalized patients. The variability in clearance among patients was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients. We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underexposed compared to their outpatient counterparts, as well as hospitalized patients who survived vs who died within 12 weeks of hospitalization.

Whole blood RNA signatures in tuberculosis patients receiving H56:IC31 vaccine as adjunctive therapy.

Therapeutic vaccination in tuberculosis (TB) represents a Host Directed Therapy strategy which enhances immune responses in order to improve clinical outcomes and shorten TB treatment. Previously, we have shown that the subunit H56:IC31 vaccine induced both humoral and cellular immune responses when administered to TB patients adjunctive to standard TB treatment (TBCOX2 study, NCT02503839). Here we present the longitudinal whole blood gene expression patterns in H56:IC31 vaccinated TB patients compared to controls receiving standard TB treatment only. The H56:IC31 group (N=11) and Control group (N=7) underwent first-line TB treatment for 182 days. The H56:IC31 group received 5 micrograms of the H56:IC31 vaccine (Statens Serum Institut; SSI, Valneva Austria GmbH) intramuscularly at day 84 and day 140. Total RNA was extracted from whole blood samples collected in PAXgene tubes on days 0, 84, 98, 140, 154, 182 and 238. The expression level of 183 immune-related genes was measured by high-throughput microfluidic qPCR (Biomark HD system, Standard BioTools). The targeted gene expression profiling unveiled the upregulation of modules such as interferon (IFN) signalling genes, pattern recognition receptors and small nucleotide guanosine triphosphate (GTP)-ases in the vaccinated group compared to controls two weeks after administration of the first H56:IC31 vaccine. Additionally, the longitudinal analysis of the Adolescent Cohort Study-Correlation of Risk (ACS-COR) signature showed a progressive downregulation in both study arms towards the end of TB treatment, in congruence with reported treatment responses and clinical improvements. Still, two months after the end of TB treatment, vaccinated patients, and especially those developing both cellular and humoral vaccine responses, showed a lower expression of the ACS-COR genes compared to controls. Our data report gene expression patterns following H56:IC31 vaccination which might be interpreted as a lower risk of relapse in therapeutically vaccinated patients. Further studies are needed to conclude if these gene expression patterns could be used as prognostic biosignatures for therapeutic TB vaccine responses.

Role of the IL8 rs4073 polymorphism in central nervous system toxicity in patients receiving multidrug-resistant tuberculosis treatment.

To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

A Case of Generalized Cryptococcal Infection in an HIV-Infected Patient with Coinfections of Cytomegalovirus and Tuberculosis

This case report presents the observation of a patient with HIV infection diagnosed with a combination of several opportunistic infections, including cryptococcosis, cytomegalovirus infection and tuberculosis. The patient underwent treatment at the National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine and the Institute of Epidemiology and Infectious Diseases named after L.V. Gromashevsky NAMS of Ukraine.HIV infection was detected at the Institute of Phthisiology and Pulmonology during an examination for exudative pleuritis. Initial evaluation raised suspicion of tuberculous exudative pleuritis. Mycobacterium tuberculosis was not detected in the biopsy material using the Xpert MTB/RIF method. Morphological analysis indicated a rare variant of cryptococcal infection involving intrathoracic lymph nodes and pleura. Additional testing revealed a positive cryptococcal antigen. Cryptococci were also identified in the cerebrospinal fluid. Cytomegalovirus chorioretinitis was diagnosed. The patient was treated according to the opportunistic infection management protocol. Antiretroviral therapy (TDF, FTC, DTG — tenofovir, emtricitabine, dolutegravir) was initiated after six weeks. The patient received prophylaxis for Pneum­cystis pneumonia with cotrimoxazole and for tuberculosis with isoniazid. One month after starting antiretroviral therapy, the patient developed a febrile illness. Further examination revealed infiltrative pulmonary tuberculosis. Repeat bacteriological testing detected rifampicin-susceptible Mycobacterium tuberculosis. The patient received standard tuberculosis treatment (2HRZE/4HR) and achieved a cure.This case highlights the diagnosis and treatment of a patient with acquired immunodeficiency syndrome and multiple secondary infections. Despite advanced immunodeficiency, timely and adequate medical interventions resulted in high treatment efficacy, contributing to increased life expectancy and improved quality of life in individuals living with HIV.

PRIMARY SUPRARENAL GLANDULAR TUBERCULOSIS MIMICKING A MALIGNANT TUMOR

ABSTRAK&#x0D; Objective: Our case demonstrates effective tuberculosis-related Addison's disease care with laparoscopic adrenalectomy and anti-tuberculosis medication. Case(s) Presentation: A 43-year-old patient complained of left flank pain for two months before admission, unexplained weight loss, general weakness, decreased appetite, and without long-term cough. The physical examination resulted in hyperpigmentation on the fingers of both hands. MRI revealed an enlarged left adrenal gland and the blood test showed elevated cortisol to 1668 mmol/L. Three-port left laparoscopic transperitoneal adrenalectomy was used. Histopathology results showed epitheloid histiocytes that formed granulomas with caseous necrosis and Datia Langerhans cells referring to tuberculosis; no malignancy was found from the same sample. Discussion: Addison's illness is the primary cause of tuberculosis. Due to the widespread use of anti-TB medications, the incidence of adrenal tuberculosis has been on the decline recently; nonetheless, in developing nations, tuberculosis is still the predominant cause of Addison's disease. Conclusion: Surgery and standard treatment for extrapulmonary tuberculosis were adequate to diagnose and alleviate the symptoms of cortisol disturbance caused by Addison’s disease.&#x0D; Keywords: Endocrine glands, adrenalectomy, tuberculosis endocrine.

Evaluating the effectiveness of first-Line anti-tuberculosis in Al Dhafra Hospitals

Background: Tuberculosis (TB) continues to be a significant public health issue despite extensive efforts to control it. The standard treatment for TB involves the use of first-line anti-TB drugs administered at a standard dose. However, the effectiveness of this treatment can vary between individual patients, resulting in differing cure rates.&#x0D; Methodology: The objective of this retrospective study was to assess the effectiveness and safety of first-line generic anti-TB medications administered at Liwa Hospital in the Al Dhafra Region. Data was collected from the electronic medical records of 140 TB patients admitted to Liwa Hospital from January to December 2022. The study included patients with positive acid-fast bacillus (AFB) or polymerase chain reaction (PCR) test results, indicating active TB infection. Patients resistant to first-line anti-TB medications or with lung cancer were excluded. Data collected included demographic information, length of stay conversion time, hospital admission, prescribed medications, treatment duration, and treatment outcomes.&#x0D; Results: This study observed an average length of stay of 21 days for patients treated with first-line generic anti-TB medications at Liwa Hospital. Over 80% of the patients were discharged within 30 days of admission, indicating a positive response to the medications. Approximately 13% of the patients required a longer duration of treatment and were discharged between 30 and 60 days after admission. Only 5% of the patients had a prolonged stay of over 60 days, most of whom had co-morbidities or rifampicin resistance, but achieved AFB conversion within three months. The average conversion time for patients was 25 days, with over 92% achieving conversion within two months.&#x0D; Conclusion: This study demonstrated the efficacy and safety of first-line generic anti-TB medications in treating TB patients at Liwa Hospital. The majority of patients responded well to the medications, leading to discharge within 30 days.&#x0D; Keywords: Tuberculosis, Ethambutol, Pyrazinamide, Rifampicin, Isoniazid, First line drugs, Anti TB drugs

Ethambutol and visual assessment in England: current practice and recommendations.

Standard treatment for tuberculosis (TB) in children and adults includes an initial two-month course of ethambutol, a drug that in rare cases can cause optic neuropathy and irreversible vision loss. There is a lack of clear guidance on what vision assessments are needed before and during treatment with ethambutol, with the Royal College of Ophthalmologists, National Institute for Health and Care Excellence, British National Formulary and British Thoracic Society offering different guidance. We aimed to assess how vision is routinely tested in patients treated with ethambutol in TB services across England. An online survey developed by Public Health England was sent to all TB services in England in 2018 to assess current practice and inform the development of best practice recommendations for visual assessment of patients treated with ethambutol for TB. Sixty-six TB professionals from across England responded, a response rate of 54%. The results showed variations in practice, including when to omit ethambutol from treatment, the timing and frequency of visual assessment, the type of visual assessment, referral processes and management of visual changes. This national survey highlights the need for clear guidelines on the testing of vision for patients taking ethambutol at recommended doses, before and during treatment. We suggest a pragmatic approach to visual assessment to reduce variation in practice, proposing a stepwise pathway for patients on standard TB treatment for local adaptation.

Treatment of tuberculosis: what is new?

Never before have so many people around the world been simultaneously affected by tuberculosis. Tuberculosis is the leading cause of death from abacterial infectious disease worldwide. The World Health Organization's ambitious goal from 2014 of achieving global elimination of tuberculosis does not seem realistic, but on current trends, tuberculosis could be eliminated in the European Union by 2040. Since the beginning of 2022, there have been more innovations for the treatment of tuberculosis than in no other comparable time period before. One month of rifapentine and isoniazid is effective in treating latent tuberculosis infection. However, rifapentine is licensed in the USA but not in the EU and must be imported for individual cases. The duration of the standard treatment for tuberculosis can be shortened to four months but this treatment regimen is also based on rifapentine, in addition to isoniazid, pyrazinamide, and moxifloxacin. The approval of rifapentine in Europe is a much-needed step towards shortening the treatment of tuberculosis. With new drugs an even shorter standard treatment of only 2months is possible. The treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR-/RR-TB) has been shortened to six months, the same length as the standard treatment available in Germany. The combination of bedaquiline, pretomanid, linezolid ± moxifloxacin, cured around 90% of affected patients were cured in studies with atreatment duration of six months. With 19drugs in clinical trials, the treatment of tuberculosis is expected to continue to improve rapidly in the coming years.

THORACIC TUBERCULOUS SPONDYLITIS WITH DECOMPRESSION AND POSTERIOR STABILIZATION TREATMENT: A CASE REPORT

Introduction. Tuberculosis (TB) spondylitis is one of the most common spinal infections. The management of spinal tuberculosis is difficult due to non-specific and variable clinical manifestation that leading to delayed identification and increases the risk of disease. The early identification and treatment are very important to avoid permanent damage in the future. Method. In this research, the researcher reports a case of a patient with tuberculous spondylitis involving the thoracic vertebral body which treated by decompression and posterior stabilization treatment. Results and Analysis. The physical examination revealed a mass appears in the midline of the back. Chest CT examination without contrast revealed a mass that caused destruction and compression of the right side of the Thoracal 7 (Th 7) vertebral body, partial destruction of the right Th7 lamina, and spinal intracanal pushing to the left of the Th7 level of the spinal cord which caused the destruction of 7th and 8th posteromedial right ribs nearby. During the two months of treatment, the patient was treated with a first-line oral regimen as standard treatment for extrapulmonary TB followed by seven-month follow-up phase. At follow-up after more than 2 months of initial TB drug administration, the back pain was persisted. The patient underwent level 7 thoracic decompression by means of laminectomy and flavectomy. Histopathological examination from biopsy showed fibrous connective tissue containing epitheloid tubercles with datia langhans which suggests the presence of tuberculous spondylitis. The diagnosis was confirmed by AFB staining. Discussion. This case is important to provide recognition of the risks and phenomena of the continuing incidence of spinal TB, despite the progress made in early diagnosis and effective management.

Pharmacokinetics and Efficacy of the Benzothiazinone BTZ-043 against Tuberculous Mycobacteria inside Granulomas in the Guinea Pig Model.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is the world's leading cause of mortality from a single bacterial pathogen. With increasing frequency, emergence of drug-resistant mycobacteria leads to failures of standard TB treatment regimens. Therefore, new anti-TB drugs are urgently required. BTZ-043 belongs to a novel class of nitrobenzothiazinones, which inhibit mycobacterial cell wall formation by covalent binding of an essential cysteine in the catalytic pocket of decaprenylphosphoryl-β-d-ribose oxidase (DprE1). Thus, the compound blocks the formation of decaprenylphosphoryl-β-d-arabinose, a precursor for the synthesis of arabinans. An excellent in vitro efficacy against M. tuberculosis has been demonstrated. Guinea pigs are an important small-animal model to study anti-TB drugs, as they are naturally susceptible to M. tuberculosis and develop human-like granulomas after infection. In the current study, dose-finding experiments were conducted to establish the appropriate oral dose of BTZ-043 for the guinea pig. Subsequently, it could be shown that the active compound was present at high concentrations in Mycobacterium bovis BCG-induced granulomas. To evaluate its therapeutic effect, guinea pigs were subcutaneously infected with virulent M. tuberculosis and treated with BTZ-043 for 4 weeks. BTZ-043-treated guinea pigs had reduced and less necrotic granulomas than vehicle-treated controls. In comparison to the vehicle controls a highly significant reduction of the bacterial burden was observed after BTZ-043 treatment at the site of infection and in the draining lymph node and spleen. Together, these findings indicate that BTZ-043 holds great promise as a new antimycobacterial drug.

Treatment Strategy for Rifampin-Susceptible Tuberculosis

BackgroundTuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear.MethodsIn this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin–linezolid and bedaquiline–linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points.ResultsOf the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin–linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline–linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, −3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin–linezolid strategy group, and 85 days in the bedaquiline–linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups.ConclusionsA strategy involving initial treatment with an 8-week bedaquiline–linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB ClinicalTrials.gov number, NCT03474198.)

Rare adverse effects of anti tuberculous therapy − a case series

Tuberculosis is prevalent throughout the world and is a major public health problem in most developing countries. Standardized and directly observed treatment under NTEP (National Tuberculosis Elimination Programme) is currently recommended for drug-sensitive pulmonary tuberculosis in India. It is generally well tolerated, with few minor side effects. Severe side effects necessitating discontinuation of therapy are rare with standard TB treatment regimens. Drug-resistant tuberculosis (DR-TB) has become more common in recent years, posing a challenge to global efforts to control the disease. Therapy for DR-TB has been associated with many adverse effects. Therefore, close monitoring of patients on DR-TB therapy is necessary to ensure that adverse effects of drugs are recognized early by healthcare personnel and treated accordingly. This will improve drug compliance and, hence, treatment goals. Here we report three cases of tuberculosis who had unusual adverse effects while receiving anti-tuberculous medication, prompting drug discontinuation.