Antitubercular Therapy In Patients Research Articles

Validation of the Online Collaborative Ocular Tuberculosis Study Calculator for Tubercular Uveitis

This was the first study, to the authors' knowledge, to statistically evaluate the predictive accuracy of Collaborative Ocular Tuberculosis Study (COTS) calculator in guiding initiation of antitubercular therapy (ATT) in patients with clinically suspicious tubercular uveitis (TBU) in an international cohort. To evaluate the accuracy of a score of 4 or greater on the online COTS calculator in recommending ATT initiation. This study was an evaluation of a diagnostic test or technology. Data input required for the COTS calculator were extracted from the COTS-1 study dataset, which comprised retrospective, observational records of patients with TBU who were monitored for 12 months after treatment. Patients were recruited from international ophthalmic centers. In the absence of a traditional criterion standard, the 12-month treatment response to ATT was used to classify patients as disease positive or negative. The accuracy of clinicians at the ATT decision-making stage in the COTS-1 study was set against COTS calculator scores of 4 or greater. Diagnostic accuracy metrics, including sensitivity, specificity, positive predictive value (PPV), precision, recall, and F1 score, were computed. Data collected from January 2004 to December 2014 were analyzed. COTS calculator to guide initiation of ATT in patients with TBU. Comparison of accuracy between clinician judgment and the COTS calculator, analyzed at varying scores and further stratified by tuberculosis endemicity. Of the 492 participants (mean [SD] age, 42.3 [19.0] years; 233 male [47.3%]), application of the COTS calculator identified 225 (45.7%) with high or very high probability to start ATT (score = 4 or 5) and 111 (22.5%) with very high probability alone (score = 5). COTS-5 exhibited the highest specificity (88.7%; 95% CI, 81.4%-93.8%) compared with clinician judgment (29.6%; 95% CI, 21.4%-38.8%), and clinician judgment led in sensitivity (95.5%; 95% CI, 92.9%-97.4%) compared with COTS-5 (26%; 95% CI, 21.6%-30.7%). COTS-4 and COTS-5 balanced specificity (64.3%; 95% CI, 54.9%-73.1%) and sensitivity (48.8%; 95% CI, 43.7%-54%). PPV and sensitivity were consistently higher in the endemic group for all 3 tests. Results of this diagnostic study suggest that the COTS calculator (score ≥4) was more specific than clinician judgment for ATT initiation. Although clinician judgment is a good first step to identify all potential true positives (with high sensitivity), a second consultation with COTS-5 (with high PPV) may lead to less false positives. This tool, apt for high-prevalence, low-resource settings, recommends ATT more selectively for genuine TBU cases. Large prospective studies are essential to explore potential improvements in the calculator's sensitivity.

Assessment of CT perfusion indices of the clinicoradiological response to anti-tubercular therapy in patients with intestinal tuberculosis

To explore the possibility of using a novel technique, CT perfusion imaging, to monitor the response to anti-tubercular therapy (ATT) in patients with intestinal tuberculosis. A prospective observational study was performed in adults with treatment naive-intestinal tuberculosis. Clinical, endoscopic, and conventional radiological findings of patients were compared at baseline and post-ATT. CT perfusion imaging was performed with recording of six perfusion parameters (blood flow, blood volume, mean transit time, time to peak, maximum peak intensity, and permeability/blood flow extraction). Twenty-two patients (13 women, 59%) with a median age of 25 years were recruited. The terminal ileum and ileocaecal junction were the most frequent sites of involvement (59%), with multiple segments of the intestine being involved in 16 patients (73%). Median duration of ATT was 6 months (range 6-10 months). Complete clinical response was observed in 22/22 (100%) patients, endoscopic response in 12/12 (100%) patients, and radiological response in 10/13 (76%) patients. There was a significant decrease in mean blood flow, blood volume, maximum peak intensity, and an increase in mean transit time and time to peak on follow-up CT perfusion imaging performed after 6 months of ATT. Significant alterations in CT perfusion parameters were demonstrated following treatment, consistent with a decline in inflammation and vascularity. CT perfusion imaging of the bowel is a novel means to assess the radiological response to ATT in intestinal tuberculosis, although at the cost of a higher dose of radiation exposure.

Heteroresistance to rifampicin & isoniazid in clinical samples of patients with presumptive drug-resistant tuberculosis in Central India.

A combination of resistant and susceptible Mycobacterium tuberculosis (MTB) isolated from clinical specimens is referred to as heteroresistance. Heteroresistance leads to difficulties in drug resistance testing and may adversely affect treatment outcomes. The present study estimated the proportion of heteroresistance among MTB in clinical samples of presumptive drug-resistant tuberculosis (TB) patients in Central India. A retrospective analysis of data generated from line probe assay (LPA) at a tertiary care hospital in Central India between January 2013 and December 2018 was carried out. A heteroresistant MTB in a sample was indicated by the presence of both wild-type and mutant-type patterns on an LPA strip. Data analysis was carried out on interpretable 11,788 LPA results. Heteroresistance in MTB was detected in 637 (5.4%) samples. Of these, heteroresistance in MTB was detected in 413 (64.8%), 163 (25.5%) and 61 (9.5%) samples with respect to rpoB, katG and inhA genes, respectively. Heteroresistance is considered a preliminary step in the development of drug resistance. Delayed or suboptimal anti-tubercular therapy in patients with heteroresistance of MTB may elicit full clinical resistance and negatively impact the National TB Elimination Programme. Further studies are, however, needed to determine the impact of heteroresistance on treatment outcomes in individual patients.

Cytokine response to antitubercular therapy in patients with human immunodeficiency virus and tuberculosis coinfection with respect to CD4 count and viral load − A pilot study

Introduction and Background: Monitoring of efficacy of antitubercular treatment (ATT) in patients with human immunodeficiency virus (HIV) and tuberculosis (TB) coinfection is more often based on clinical judgment. Having an objective biomarker monitor, the treatment response to ATT is urgently required in HIV-TB coinfection. Methodology: Fifty patients of diagnosed HIV infection with TB as opportunistic infection were enrolled. Baseline CD4 and HIV viral load were done. Serum cytokine levels of IFN γ, IL-10, IL-2, and interferon gamma-inducible protein-10 (IP-10) were assessed at baseline and after 2 months of initiation of ATT. Results: Out of fifty patients, 43 (86%) were male and 7 (14%) were female. The mean age of the patients was 39 years. The median CD4 count was 342 cells/uL, and the mean plasma HIV viral load was 3,05,093 copies/ml. Sputum for AFB was positive in 15 (30%) patients. The levels of interferon-gamma (INF γ), interleukin (IL)-4, and IL-10 have shown a statistically significant decline over 2 months [Table 1] with a P = 0.005, <0.001, and 0.023, respectively. There was a significant correlation between IP-10 and CD4 count in male patients as assessed by Pearson correlation coefficient (P = 0.048). Conclusion: The levels of INF γ, IL-4, and IL-10 have shown a statistically significant decline over 2 months [Table 1] with a P = 0.005, <0.001, and 0.023, respectively. There was a significant correlation between IP-10 and CD4 count in male patients.

Effect of Body Weight on Cytokine Response to Anti-tubercular Therapy in Patients with HIV Infection and Tuberculosis

Effect of Body Weight on Cytokine Response to Anti-tubercular Therapy in Patients with HIV Infection and Tuberculosis

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 447 Patients with Tubercular Intermediate Uveitis and Panuveitis

ABSTRACT Purpose: Tubercular intermediate uveitis (TIU) and panuveitis (TBP) are difficult to manage because of limitations in diagnostic tools and lack of evidence-based treatment guidelines. The Collaborative Ocular Tuberculosis Study (COTS) analyzed treatment regimens and therapeutic outcomes in patients with TIU and TBP. Methods: Multicentre retrospective analysis. Results A total of 138 TIU and 309 TBP patients were included. A total of 382 subjects received antitubercular therapy (ATT) (n = 382/447; 85.4%) and 382 received corticosteroids (n = 382/447; 85.4%). Treatment failure was observed in 78 individuals (n = 78/447; 17.4%), occurring less frequently in patients receiving ATT (n = 66/382; 17.2%) compared to those who did not (n = 12/65; 18.5%). The study did not show any statistically significant therapeutic effect of ATT in patients with TIU and TBP. Conclusion Taking into account the limitations of the retrospective, non-randomized study design, resultant reliance on reported data records, and unequal size of the samples, the current study cannot provide conclusive evidence on the therapeutic benefit of ATT in TIU and TBP.

Serial measurements of faecal calprotectin may discriminate intestinal tuberculosis and Crohn's disease in patients started on antitubercular therapy.

Response to antitubercular therapy (ATT) is often used to differentiate intestinal tuberculosis (ITB) from Crohn's disease. Role of non-invasive biomarkers to predict mucosal response to ATT is unclear. A prospective study to compare faecal calprotectin and serum C-reactive protein (CRP) levels at diagnosis, 2 and 6 months of ATT in patients with suspected ITB started on ATT was done. The patients were eventually divided into two groups: ITB or alternative diagnosis (OTH). Decline of calprotectin and CRP levels was used to compute area under the receiver operating characteristic (AUROC) to predict mucosal healing at 2 months. Thirty-seven patients (mean age: 34.95 ± 16.35 years, 23 males) were included and 28 (75.67%) were diagnosed as ITB while nine (24.32%) had alternative diagnosis (OTH). The median faecal calprotectin values of ITB and OTH groups at baseline, 2 months and 6 months were 216 and 282 µg/g (P = 0.466), 43 and 216 µg/g (P = 0.003), and 26 and 213 µg/g (P < 0.001), respectively. The median CRP values at baseline, 2 months and 6 months were 18 and 30 mg/L (P = 0.767), 4.7 and 15 mg/L (P = 0.025), and 3 and 10.85 mg/L (P = 0.068), respectively. The AUROC of percent decline in faecal calprotectin and serum CRP at 2 months for mucosal healing were 0.8287 [95% confidence inteval (CI) 0.6472-1] and 0.6018 (95% CI 0.4079-0.7957), respectively. Faecal calprotectin can help in assessing response to therapy in suspected ITB patients started on empirical ATT.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis—Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis

An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Pott’s Spine with Tubercular Meningitis and Primary Optic Atrophy: An Enigma with a Rare Cautionary Tale

AbstractTuberculosis of spine, known as Pott’s spine, is a significant health risk. Misdiagnosis or delayed diagnosis with lack of timely interventions lead to serious neurological complications and is associated with morbidity and mortality. We present a case of Pott’s spine who developed tubercular meningitis with decreased vision due to primary optic atrophy, to highlight the significance of thorough clinical and neuroradiological workup with instillation of prompt antitubercular therapy in patients of central nervous system tuberculosis (CNS TB). This association of Pott’s spine with decreased vision secondary to primary optic atrophy due to tubercular involvement of the second cranial nerve is very rare. Here, associated risk factors, varied clinical presentations, complications, and treatment of CNS TB are reviewed.

The Role of Anti-tubercular Therapy in Patients with Presumed Ocular Tuberculosis

Objective: To analyze the factors affecting the treatment outcome in patients with presumed ocular tuberculosis on anti-tubercular therapy (ATT).Methods: Retrospective chart review of patients with presumed ocular tuberculosis seen at a tertiary referral eye care center in the United Kingdom. Failure was defined as recurrence of inflammation within 6 months of completion of ATT.Results: There were a total of 175 patients with presumed ocular tuberculosis who had ATT. Patients with intermediate uveitis or panuveitis and those on immunosuppressive therapy had higher odds of treatment failure (p < 0.05) while those with more than 9 months of ATT (77, 79.38%) had less likelihood of failure.Conclusion: We present the largest case series of patients with presumed ocular tuberculosis in a low endemic area treated with ATT. Longer duration of treatment resulted in reduced risk of recurrence of inflammation, whereas immunosuppression adversely affected the final treatment outcome.

Clinical and Biochemical Profile of Tuberculosis in Patients with Liver Cirrhosis

Introduction: Tuberculosis (TB) is endemic in India. Standard antitubercular therapy (ATT) though highly effective has defined hepatotoxicy. There is paucity of data on prevalence of tuberculosis and ATT -induced hepatotoxicity in patients with chronic liver disease. Aim: To study demographic, clinical characteristics of tuberculosis, pattern of drug induced liver injury and treatment responses to ATT in patients with liver cirrhosis. Material and Methods: All cases of liver cirrhosis diagnosed with TB between January 2010 and October 2013 were enrolled. Drug -induced liver injury (DILI) was defined as (1) an ALP, AST, or ALT value exceeding 3 times the normal upper limit if the baseline level was normal, or an ALP, AST, or ALT exceeding 2 times the baseline level if the baseline level was abnormal. Results: Sixty-seven patients had confirmed TB with underlying cirrhosis and formed the study group. The median age of cases was 52 (24–85) years and M: F ratio was 57:10. Median CTP score of patients were 8.5 (5–12) (CTP A: B: C: 7:44:16). The sites of TB included: pulmonary (25, 37%); pleural effusion (10, 15%) peritoneal (19, 28%); cervical lymph nodes (3, 4%); liver (1, 1.5%); intestines (4, 6%); and vertebra (3, 4%), brain (1, 1.5%) and disseminated (2, 3%). Thus, extrapulmonary TB was as common in the cirrhotic patients as pulmonary TB Patients with Child's Pugh status A (n = 7) received standard 4 drugs as in patients with non cirrhotic patients (RHEZ) and could tolerate well even during follow up without any drug induced toxicity. In rest of patients commonest regimen followed was combination of drugs [RHEO, n = 32) followed by HEO (n = 11), REO (n = 9) and EO (8). Drug induced toxicity was seen in 32% patients in patients started with RHEO, HEO and REO. Median time of onset of DILI was 12 days (4-34) days. Of 32 patients with (R+H) regimen in Child's B and C it could be continued for more than 2 months in 22 patients only due to DILI. Reintroduction of rifaximin was possible in 6 patients and INH in 4 patients respectively. There was no DILI related death during hospital stay. Conclusions: Extrapulmonary T.B is common in patients with cirrhosis and DILI is common in Child B and C with R+H regimen.

Antitubercular therapy in patients with cirrhosis: challenges and options.

Tuberculosis (TB) has been a human disease for centuries. Its frequency is increased manyfold in patients with liver cirrhosis. The gold standard of TB management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and ethambutol. Although good results are seen with this treatment in general, the management of patients with underlying cirrhosis is a challenge. The underlying depressed immune response results in alterations in many diagnostic tests. The tests used for latent TB have many flaws in this group of patients. Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis. Frequency of hepatotoxicity is increased in patients with liver cirrhosis, frequently leading to severe liver failure. There are no established guidelines for the treatment of TB in relation to the severity of liver disease. There is no consensus on the frequency of liver function tests required or the cut-off used to define hepatotoxicity. No specific treatment exists for prevention or treatment of hepatotoxicity, making monitoring even more important. A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.

Response to Trial of Antitubercular Therapy in Patients With Ulceroconstrictive Intestinal Disease and an Eventual Diagnosis of Crohn's Disease

Response to Trial of Antitubercular Therapy in Patients With Ulceroconstrictive Intestinal Disease and an Eventual Diagnosis of Crohn's Disease

Erythema nodosum and antitubercular therapy

OBJECTIVE: To establish the efficacy of antitubercular therapy in patients with erythema nodosum with a highly positive Mantoux test.METHODS: A retrospective analysis of all patients diagnosed with idiopathic erythema nodosum with a highly positive Mantoux reaction between 1988 and 2001 was undertaken. In the absence of any other clinical or investigative evidence of active tuberculosis they were treated with antitubercular therapy.RESULTS: Out of a total of 52 patients diagnosed with idiopathic erythema nodosum with a strongly positive Mantoux test (average of 19 mm), data could be analyzed in only 47 patients. After treatment with antitubercular drugs, new lesions stopped appearing in 45 patients within 6–8 weeks and subsided in two. The therapy was well tolerated except for jaundice in one patient and transient urticarial lesions in another.CONCLUSIONS: Antitubercular therapy definitely has a role in the management of patients with erythema nodosum, even in the absence of a detectable focus of tubercular infection, especially in regions where tuberculosis is endemic.