Anti-tuberculosis Treatment Regimen Research Articles

Key Factors Influencing Liver Function Injury in Elderly Patients with Newly Diagnosed Pulmonary Tuberculosis Complicated by Diabetes after Antituberculosis Treatment.

This study addressed the factors influencing liver injury in elderly patients newly diagnosed with pulmonary tuberculosis and diabetes after antituberculosis treatment. From January 2021 to June 2023, 218 elderly patients with early treatment of pulmonary tuberculosis (N = 218) combined with diabetes (N = 218) were collected as research subjects. All patients were treated with the same antituberculosis treatment regimen and were divided into a nonhepatotoxicity group (N = 92) and a hepatotoxicity group (N = 126) according to whether drug-induced liver injury occurred within 3 months after taking tuberculosis drugs. The levels of alanine aminotransferase and aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, albumin, lipoprotein(a), prothrombin time, and hemoglobin A1c (HbA1c) were detected by biochemical analyzer. The extent of pulmonary tuberculosis lesions was examined by computed tomography imaging. Influencing factors of antituberculosis drug-induced liver injury were analyzed by logistic multivariate analysis. The hepatotoxicity group exhibited a higher average age than the nonhepatotoxicity group (P <0.05). Additionally, there was a greater prevalence of patients with a history of alcohol consumption in the hepatotoxicity group than in the nonhepatotoxicity group (P <0.05). And the hepatotoxicity group showed a greater extent of tuberculosis lesions (P <0.05). Logistic multivariate analysis identified advanced age, body mass index of <18.5, lesion range of ≥2 lung lobes, history of alcohol consumption, and HbA1c of ≥8% as relevant factors associated with liver function impairment in older adults patients undergoing early treatment of pulmonary tuberculosis combined with diabetes after antituberculosis therapy. These findings underscore the importance of monitoring and addressing these factors during antituberculosis therapy in the elderly population to mitigate the risk of liver function impairment.

Continuous Rifampicin Therapy Induced Acute Kidney Injury in a Tuberculous Patient: A Case Report

Background: Tuberculosis (TB) presents with productive cough, hemoptysis, chest pain, fever, weight loss, and night sweats. Anti-tuberculosis treatment (ATT) can affect various organs, including the liver and kidneys. ATT-induced acute kidney injury (AKI) presents with fever, rash, nausea, vomiting, diarrhea, and abdominal pain. It occurs due to type 2 or 3 hypersensitivity and affects individuals who have previously used rifampicin or are currently using it intermittently. Case: An 60-year-old lady was diagnosed with TB and started on ATT. After a few days, she complained of reduced food intake and vomiting, yellow discoloration of the skin, abdominal pain and distention, and limb swelling. She was diagnosed as a case of ATT-induced AKI. She didn't have past exposure to rifampicin and was continuously using it this time. Conclusion: The key learning point from this case is that ATT-induced AKI can develop even when used in a continuous dosing regime and upon first time exposure despite no history of past exposure. This prompts vigilance in monitoring renal function in patients being started on ATT regimen. This is becasuse, ATT-induced AKI poses risk to patient’s life and there is a possibility of developing resistance to anti-tuberculous therapy as a result of discontinuation of treatment. Furthermore, our case suggests that, in addition to immune-mediated mechanisms described in literature for ATT-induced AKI, other pathophysiological mechanisms might also be linked to this pathology and need further research for better understanding and optimization of treatment strategies.

Unraveling Dilemmas and Lacunae in the Escalating Drug Resistance of Mycobacterium tuberculosis to Bedaquiline, Delamanid, and Pretomanid.

Delamanid, bedaquiline, and pretomanid have been recently added in the anti-tuberculosis (anti-TB) treatment regimens and have emerged as potential solutions for combating drug-resistant TB. These drugs have proven to be effective in treating drug-resistant TB when used in combination. However, concerns have been raised about the eventual loss of these drugs due to evolving resistance mechanisms and certain adverse effects such as prolonged QT period, gastrointestinal problems, hepatotoxicity, and renal disorders. This Perspective emphasizes the properties of these first-in-class drugs, including their mechanism of action, pharmacokinetics/pharmacodynamics profiles, clinical studies, adverse events, and underlying resistance mechanisms. A brief coverage of efforts toward the generation of best-in-class leads in each class is also provided. The ongoing clinical trials of new combinations of these drugs are discussed, thus providing a better insight into the use of these drugs while designing an effective treatment regimen for resistant TB cases.

Disseminated Tuberculosis: A 6-year Case Series Experience in a Tertiary Care Center.

Disseminated tuberculosis (dTB) disease is associated with a significant burden of morbidity and mortality and it requires improved awareness among clinicians. Case reports revealing the clinical and microbiological characteristics of dTB patients will help us to extend our knowledge of dTB. In our study, we have documented dTB cases followed for 6 years and revealed patients' clinical characteristics. Patients followed between 2017 and 2023 who were diagnosed with dTB in a tertiary referral hospital in Istanbul have been evaluated. Data regarding patients' characteristics, methods used in establishing the definitive diagnosis, radiological patterns in chest X-rays, extrapulmonary sites involved, antituberculosis (TB) treatment regimens received, medication side effects, and drug resistance have been examined. Descriptive statistics were performed. Clinical characteristics of 55 patients with a median age of 41 (range 20-85, 52.7% male) were examined. The most common extrapulmonary involvements in our study were the skeletal system (n = 24), central nervous system (n = 7), and genitourinary tract (n = 7). Isoniazid (INH) resistance was detected in four patients. Mono resistance was reported for pyrazinamide in one patient. Multidrug resistance was detected in two patients and one of them was also resistant to ethambutol. Preextensively, drug resistance was reported in three patients. Another three patients were evaluated as resistant to both INH and streptomycin. Migrating from a high TB burden country and comorbidities such as diabetes mellitus, human immunodeficiency virus, and rheumatoid arthritis that are related to immunocompromisation are thought to be risk factors for dTB.

Perinatal tuberculosis-An approach to an under-recognized diagnosis.

Tuberculosis (TB) in young infants (<3 months of age), often referred to as perinatal TB, is underdiagnosed, leading to severe morbidity and high mortality. Perinatal TB includes both congenital and postnatal transmission of Mycobacterium tuberculosis. We aimed to increase an awareness of TB in neonates and young infants and to provide guidance on the assessment and management when in contact with mothers with TB during or soon after pregnancy. Approximately 217,000 pregnant women develop TB annually; if they are not diagnosed and treated during pregnancy, their infants are at high risk of adverse birth outcomes and TB disease. Although safe and effective antituberculosis treatment regimens are available during pregnancy, the diagnosis of TB is challenging. Infants born to mothers newly diagnosed with TB, not receiving any effective treatment or with cultures not yet negative, should be assessed for TB disease or M. tuberculosis infection. TB preventive therapy should be instituted if the infant is clinically well but exposed to TB, while prompt initiation of TB treatment is essential if TB disease is presumed. HIV status of mother and infant should be considered as this will affect the management. Further research is needed for the diagnosis and prevention of TB during pregnancy, an early diagnosis of TB in infants, and antituberculosis drug pharmacokinetics in young infants.

In silico virtual screening for the identification of novel inhibitors against dihydrodipicolinate reductase (DapB) of Mycobacterium tuberculosis, a key enzyme of diaminopimelate pathway.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) is one of the most devastating infectious diseases afflicting a large number of human lives. In spite of the availability of several drugs for treating TB, emergence of drug-resistant strains of the pathogen has made treatment and eradication of TB a challenging task. Hence, there is an imperative need for new intervention strategies to target M. tb. The enzymes of the diaminopimelate pathway, involved in lysine biosynthesis as well as in cell wall biosynthesis, have been considered as important anti-TB drug targets. One such enzyme is dihydrodipicolinate reductase (DapB), catalyzing the reduction of 2,3-dihydrodipicolinic acid to 2,3,4,5-tetrahydro-dipicolinic acid by utilizing NADH/NADPH as its cofactor. Here, we have generated an antisense knockdown mutant strain of dapB and demonstrated a crucial role of dapB in the in vitro and intracellular growth of M. tb. Further, in silico virtual screening was performed by employing a library of ~95,000 compounds for the identification of inhibitory molecules against DapB. The molecules with high docking scores were screened against the enzymatic activity of DapB to determine their IC50 values. Further, hit molecules that inhibited DapB were screened against the M. tb growth in broth culture and inside macrophages. The molecules exhibiting M. tb inhibition were also evaluated for their cytotoxicity against various mammalian cell lines. In summary, we have identified a lead molecule, B59, with an IC50 value of 11 µg/mL and MIC99 value of 20 µg/mL, which can be further optimized to develop potent inhibitory compounds against M. tb DapB. IMPORTANCE Non-compliance to lengthy antituberculosis (TB) treatment regimen, associated side effects, and emergence of drug-resistant strains of Mycobacterium tuberculosis (M. tb) emphasize the need to develop more effective anti-TB drugs. Here, we have evaluated the role of M. tb dihydrodipicolinate reductase (DapB), a component of the diaminopimelate pathway, which is involved in the biosynthesis of both lysine and mycobacterial cell wall. We showed that DapB is essential for the in vitro as well as intracellular growth of M. tb. We further utilized M. tb DapB, as a target for identification of inhibitors by employing in silico virtual screening, and conducted various in vitro screening assays to identify inhibitors with potential to inhibit DapB activity and in vitro and intracellular growth of M. tb with no significant cytotoxicity against various mammalian cell lines. Altogether, M. tb DapB serves as an important drug target and a hit molecule, namely, 4-(3-Phenylazoquinoxalin-2-yl) butanoic acid methyl ester has been identified as an antimycobacterial molecule in our study.

Effect of seven anti-tuberculosis treatment regimens on sputum microbiome: a retrospective analysis of the HIGHRIF study 2 and PanACEA MAMS-TB clinical trials

Respiratory tract microbiota has been described as the gatekeeper for respiratory health. We aimed to assess the impact of standard-of-care and experimental anti-tuberculosis treatment regimens on the respiratory microbiome and implications for treatment outcomes. In this retrospective study, we analysed the sputum microbiome of participants with tuberculosis treated with six experimental regimens versus standard-of-care who were part of the HIGHRIF study 2 (NCT00760149) and PanACEA MAMS-TB (NCT01785186) clinical trials across a 3-month treatment follow-up period. Samples were from participants in Mbeya, Kilimanjaro, Bagamoyo, and Dar es Salaam, Tanzania. Experimental regimens were composed of different combinations of rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), moxifloxacin (M), and a new drug, SQ109 (Q). Reverse transcription was used to create complementary DNA for each participant's total sputum RNA and the V3-V4 region of the 16S rRNA gene was sequenced using the Illumina metagenomic technique. Qiime was used to analyse the amplicon sequence variants and estimate alpha diversity. Descriptive statistics were applied to assess differences in alpha diversity pre-treatment and post-treatment initiation and the effect of each treatment regimen. Sequence data were obtained from 397 pre-treatment and post-treatment samples taken between Sept 26, 2008, and June 30, 2015, across seven treatment regimens. Pre-treatment microbiome (206 genera) was dominated by Firmicutes (2860 [44%] of 6500 amplicon sequence variants [ASVs]) at the phylum level and Streptococcus (2340 [36%] ASVs) at the genus level. Two regimens had a significant depressing effect on the microbiome after 2 weeks of treatment, HR20mg/kgZM (Shannon diversity index p=0·0041) and HR35mg/kgZE (p=0·027). Gram-negative bacteria were the most sensitive to bactericidal activity of treatment with the highest number of species suppressed being under the moxifloxacin regimen. By week 12 after treatment initiation, microbiomes had recovered to pre-treatment level except for the HR35mg/kgZE regimen and for genus Mycobacterium, which did not show recovery across all regimens. Tuberculosis culture conversion to negative by week 8 of treatment was associated with clearance of genus Neisseria, with a 98% reduction of the pre-treatment level. HR20mg/kgZM was effective against tuberculosis without limiting microbiome recovery, which implies a shorter efficacious anti-tuberculosis regimen with improved treatment outcomes might be achieved without harming the commensal microbiota. European and Developing Countries Clinical Trials Partnership and German Ministry of Education and Research.

Effects of antituberculosis treatment on pregnancy outcomes in infertile women with genital tuberculosis: a systematic review

ObjectivesTo evaluate the efficacy of antituberculosis therapy on pregnancy outcomes in infertile women with genital tuberculosis.DesignSystematic review.Data sourcesWe searched in PubMed/MEDLINE, CENTRAL and EMBASE up to 15 January 2023. Additionally,...

Rapid detection of fluoroquinolone resistance in Mycobacterium tuberculosis using a novel multienzyme isothermal rapid assay.

Simple, rapid, and accurate detection of Fluoroquinolone (FQ) resistance is essential for early initiation of appropriate anti-tuberculosis treatment regimen among rifampicin-resistant tuberculosis (RR-TB). In this study, we developed a new assay, which combines multienzyme isothermal rapid amplification and a lateral flow strip (MIRA-LF), to identify the mutations on codons 90 and 94 of gyrA for detecting levofloxacin (LFX) resistance. Compared to conventional phenotypic drug susceptibility testing, the new assay detected fluoroquinolone resistance with a sensitivity, specificity, and accuracy of 92.4%, 98.5%, and 96.5%, respectively. Thus, these characteristics of the newly developed MIRA-LF assay make it particularly useful and accurate for detecting FQ resistance in Mycobacterium tuberculosis in resource-limited condition.

Esophageal anthracosis occurred after treatment of esophageal tuberculosis secondary to mediastinal tuberculous lymphadenitis: a rare case report

BackgroundAnthracosis is a disease generally considered to be in the lungs resulting from exposure to industrial dust in the workplace. Esophageal anthracosis is a fairly rare phenomenon and shows a strong correlation with tuberculosis. Moreover, esophageal involvement in tuberculosis is also rare. We here present an extremely rare case in which follow-up gastroesophageal endoscopy revealed a mass with a sunken, black area in the center and raised ring-like pattern in the surrounding mucosa resembling malignant melanoma. Uncovering the patient’s tuberculosis history finally avoided a misdiagnosis or overtreatment.Case presentationA 67-year-old male patient was admitted to the hospital due to “repeated chest pain for 1 month”. Endoscopic ultrasonography and contrast-enhanced CT scans revealed a mass adjacent to the esophageal wall with unclear boundaries. Aspiration biopsy confirmed that esophageal tuberculosis was caused by nearby mediastinal tuberculous lymphadenitis. After a standard anti-tuberculosis treatment regimen, the patient achieved a favorable prognosis. The follow-up gastroesophageal endoscopy showed a sunken black lesion with elevated peripheral mucosa replacing the original tuberculous mass, which was thought to be anthracosis, a disease that rarely occurs in the esophagus.ConclusionThe diagnosis of tuberculosis should be taken into consideration when a submucosal mass appears in the middle part of the esophagus. Endoscopic ultrasonography can effectively contribute to a definite diagnosis. Moreover, this is the first case of esophageal anthracosis observed only 1 year after the treatment of tuberculosis, indicating esophageal anthracosis can be a short-term disease. The traction of the reduction of tubercular mediastinal lymph nodes after anti-tuberculosis treatment may create a circumstance for pigmentation or dust deposition.

The outcome of different forms and regiments of antituberculous drugs in Assiut Governorate

Introduction The prescription of effective and well-tolerated antituberculosis (TB) treatment regimen is an important step in the management of TB. Objective To compare the outcome of fixed-dose combination (FDC) therapy versus standard treatment (ST) in treatment of pulmonary tuberculosis (PTB) and extrapulmonary TB in Assiut Governorate. Patients and methods In this prospective cross-sectional analytic study, 120 patients were included. Overall, 60 had PTB based on sputum-positive acid-fast bacilli, and 60 had extrapulmonary TB based on biopsy or culture from the affected sites. Patients were classified into two groups: 80 patients received FDC in the form of four-drug combinations in the intensive phase and the two-drug combination therapy in the continuation phase (group 1) and 40 patients received ST in the form of four separate drugs in the intensive phase and the two separate drugs in the continuation phase (group 2). Follow-up of clinical data, laboratory markers, sputum conversion in PTB during the course of treatment, drug tolerance, compliance, and developing of adverse effect was done in both groups. Results There is no statistically significant difference between both groups regarding improvement of the fever and anorexia and weight loss (P > 0.05 for each). Moreover, there are no statistically significant changes in the sputum conversion between both groups after 2, 4, and 6 months, respectively. There is a statistically significant increase in the percentage of the patients, with increase of alanine aminotransferase, aspartate aminotransferase, and bilirubin level along the course of the treatments in patients receiving FDC and ST (P < 001) but still within normal limits, and there is no need to stop or change the therapy. No significant difference between the two groups regarding the adverse effects such as nausea, vomiting, anorexia, blurred vision, peripheral neuropathy, arthralgia, and skin rash is recorded. Conclusion Both FDC and ST have comparable results, with no superiority of either one over the other.

Improve the clinical research and standardize the management of pleural diseases

Based on the clinical evidence obtained during the past decade, we reviewed herein the evidences in the treatment of 5 types of common pleural diseases. (1) Therapeutic pleural interventions are not recommended for patients with malignant pleural effusion (MPE) who are asymptomatic. In patients with symptomatic MPE, large-volume thoracentesis should be performed in MPE patients to figure out if the patient's symptoms are related to the effusion and/or if the lung is expandable; if so, indwelling pleural catheters and/or talc pleurodesis can be used as first-line definitive intervention. Indwelling pleural catheters, but not pleurodesis should be used in those with symptomatic MPE with nonexpandable lung, failed pleurodesis, or loculated effusion. (2) Randomized controlled trials concerning tuberculous pleurisy management are always scarce. Based on the data from pulmonary tuberculosis trials, it can be accepted that anti-tuberculosis treatment regimen for tuberculous pleurisy with isoniazid, rifampin, and pyrazinamide for two months followed by four months of two drugs, isoniazid and rifampin. (3) A combination of tissue plasminogen activator and deoxyribonuclease can be instilled intrapleurally as the initial treatment, or as a follow-up treatment after surgery for pleural infection. The recommended dosages are as follows: tissue plasminogen activator 10 mg, twice a day, deoxyribonuclease 5 mg, twice a day. (4) The randomized controlled trial has provided evidence that conservative management is an acceptable alternative to interventional management for moderate-to-large primary spontaneous pneumothorax. (5) For patients with malignant pleural mesothelioma, nivolumab plus ipilimumab is capable of significantly improving the overall survival of patients versus platinum plus pemetrexed chemotherapy, supporting the use of this regimen as the first-line treatment for these patients, regardless of histological subtype.

Isoniazid and Rifampicin Tuberculosis Drug Resistance in HIV Endemic Region of Western Kenya

Background: Tuberculosis drug resistance is often associated with inadequate anti-tuberculosis treatment regimen resulting to mutations that confers resistance to anti-tuberculosis agents. This is aggravated by synergetic relationship between Tuberculosis and HIV (Human Immunodeficiency Virus). Over 25% of Global Tuberculosis deaths occur in Africa and Kenya is one of the 30 high burden countries that together account for more than 80% of the world’s TB cases. According to World Health Organization, in 2018, Multi drug resistant Tuberculosis prevalence in Kenya was 1.3% in new cases and 4.4% in retreatment cases. Kisumu County recorded the second highest HIV prevalence at 18.6% against the national prevalence of 4.5% in 2020. The extent of regional burden of DR-TB and HIV co-infection has not been exactly well-defined in Western Kenya. Methods: This was a prospective cross sectional study that aimed to explore the association between Tuberculosis drug resistance and HIV status among new and previously treated pulmonary tuberculosis cases in Kisumu County, Kenya. Tuberculosis clinical suspects were recruited into the study and classified as HIV positive or negative based on their clinical data. Sputum samples from tuberculosis clinical suspects were subjected to fluorescent microscopy, phenotypic culture and line probe assay. Results: Out of a sample of 256, response rate was 216 of which HIV positive cases were 119(55.1%) and negative were 97 (44.9%). The study found that out of 11 that were phenotypic Isoniazid resistance 8(6.7%) were from HIV positive cases while 3 (3.2%) were from HIV negative cases. Phenotypic rifampicin resistance among the HIV positive were 8 (6.7%) while HIV negative were 2 (2.1%). All the 2(1.7%) MDR cases were from HIV positive participants. The study found out that HIV status and Tuberculosis cases were significantly associated at p&lt;.05. HIV positive cases were more likely associated with retreatment cases (OR=1.4,95CI:1.00-1.90) compared to new cases. The study found out that the common mutant probe among the HIV positive was katG MUT1 4(2.6%), while mutant probes among the HIV negative were in hA MUT1 1(0.7%), katG MUT1 1(0.7%) and roB MUT2A 1(0.7%). Wild type gene deletion among the HIV positive cases were observed in probes katG WT 3(2.1%), roB WT7, katG WT 1(0.7%) while wild type gene deletion among the HIV negative cases were inhA WT1 1(0.7%), in hA WT1/inhAWT2 1(0.7%), katG WT 1(0.7%). Conclusion: Interventions specific to HIV-endemic areas are urgently needed to block tuberculosis drug resistance transmission. Development and improvement of the efficacy of interventions will require a greater understanding of the transmission of multidrug-resistant tuberculosis in HIV-endemic settings like Kisumu County, Western Kenya.

POS-769 ALLOGRAFT OUTCOMES, SAFETY AND EFFICACY OF QUINOLONE BASED AND RIFAMPIN BASED REGIMENS FOR THE TREATMENT OF TUBERCULOSIS IN KIDNEY TRANSPLANT RECIPIENTS

Among patients with kidney transplant receiving rifampicin-based anti-tuberculosis treatment regimen, the need for increased dose of immunosuppressants along with frequent drug level monitoring, imposes significant financial and economic burden in this disadvantaged population, more so in the middle- or low-income countries. However, as yet there are no prospective randomised studies comparing the efficacy of levofloxacin-based anti-tuberculosis treatment with rifampicin-based anti-tuberculosis treatment in kidney transplant recipients. The present study was designed to study the efficacy, safety and effect on allograft function in levofloxacin- versus rifampicin-based anti-tuberculosis treatment regimen. We conducted a prospective randomized study at the Post Graduate Institute of Medical Education and Research, Chandigarh between the period January 2020 to June 2021. The study included 20 kidney transplant recipients who developed TB post-kidney transplant and were randomized to receive 12 months of anti-tuberculosis treatment with either a rifampicin-based anti- tuberculosis treatment or levofloxacin-based anti-tuberculosis treatment regimen and were followed up for the duration of their treatment. All patients were on a calcineurin inhibitor based maintenance immunosuppression regimen, with 90% receiving tacrolimus and 10% on cyclosporine. Out of total 20 patients,40% had pulmonary TB, 50% had extra-pulmonary TB and 10% had pulmonary and extra-pulmonary TB. Tuberculosis was diagnosed by histopathology in 15%, microbiological in 40% and clinical-radiological in 45%. Anti-tuberculosis treatment was commenced within 4 weeks of onset of symptoms in 55% of the patients and, within 6 weeks in all patients. In the rifampicin-based anti-tuberculosis treatment group, 40% had to discontinue treatment and switch to levofloxacin-based anti-tuberculosis treatment, in view of drug related adverse effects or difficulty in maintaining immunosuppressant levels. All patients in the levofloxacin-based anti-tuberculosis treatment group remained on levofloxacin for the duration of treatment. All patients responded to anti- tuberculosis treatment and there was no mortality observed in the cohort during the period of follow- up. In our study levofloxacin-based anti-tuberculosis treatment had similar allograft outcomes as rifampicin-based anti-tuberculosis treatment and appeared to be associated with less adverse drug effects, lesser chance of discontinuation of drug therapy and more stable calcineurin inhibitor drug levels. Given these attributes, the study findings lend support to the use of Levofloxacin-based anti-tuberculosis treatment as the first line therapy regimen for kidney transplant recipients with TB who are on calcineurin inhibitor based maintenance immunosuppression regimen. The findings of this study serve as pilot towards future larger randomized trial to prospectively compare the two treatment regimens.

Adverse drug reaction profile of daily regimen antituberculosis treatment.

The objective was to estimate the proportion of adverse drug reactions (ADRs) to daily regimen antituberculosis treatment (ATT) among the ADRs received in the ADR monitoring center (AMC) of the institution and to describe its pattern. This was a descriptive study conducted in the Department of Pharmacology of a Government Medical College in Central Kerala and the period under study was October 2017-June 2020. The data on ADR were entered into a structured pro forma and data were analyzed using SPSS for Windows Version 16.0 (SPSS Inc., Chicago, USA). Of the 643 ADRs, 98 (15.24%) were suspected to be due to the daily regimen of ATT. The most common organ system affected was hepatobiliary 46 (46.9%) namely hepatitis in 35 and asymptomatic elevated liver enzymes in 11 followed by eye with 26 reports of decreased vision. In 96 (97.95%), the suspected ADR had probable causality and in 2 (2.04%) it was possible. Seventy-seven (78.6%) ADR reports were serious as well as moderate-level 4b in severity and 57 (58.16%) were probably preventable. The mean days of onset of ADR after starting the ATT regimen were 56.40 ± 58.29 days (range 1-180). Decrease in vision with a mean duration of 125.23 ± 55.46 days had the longest latency in onset among all the ADRs. Of all the ADRs reported to AMC 15.24% were due to the daily regimen of ATT. Hepatitis was the most common ADR encountered followed by decrease in vision. The majority of the ADRs were probable in causality, serious, moderate-level 4b in severity, and probably preventable.

Incidence rate and time to serious adverse events among rifampicin resistant tuberculosis patients in Georgia treated with new and repurposed anti-tuberculosis drugs, 2016-2018

Considering the complexity of second-line anti-tuberculosis (TB) treatment regimens, the management of drug-resistant TB (DR-TB) in Georgia remains a major challenge. Since the introduction of new and repurposed anti-TB medications, the implementation of active TB Drug Safety Monitoring (aDSM) was a critical program component to help establish safety and manage all treatment related Serious Adverse Events (SAEs). In our study, we aimed to describe the occurrence, characteristics and timing of SAE among patients with Rifampicin Resistant and Multi-Drug Resistant TB (RR/MDR-TB) receiving new and/or repurposed anti-TB medications (bedaquiline, delamanid, linezolid, clofazimine, imipenem) during the period of 2016–2018 in Georgia and identify predictors of SAE. The data were obtained from the medical charts, electronic database and standardized aDSM reports During 2016–2018 period in total 970 people with RR/MDR-TB were notified in Georgia and 388 of them received new and/or repurposed TB drugs as part of their treatment regimen and all were included into the study. The results showed a total of 73 SAEs registered among 49 (12.6%) patients receiving new and/or repurposed drugs. The overall SAE incidence rate per 100 person-months was 1.16. The severity of the majority of the SAEs (46.6%) was grade III and 21.9% were grade IV. The most common SAE reported was hepatotoxicity, with an incidence of 0.26 per 100 person-month (n=16, 21.9%) followed by cardiotoxicity with an incidence of 0.16 per 100 person-month (n=10, 13.7%). Median time to SAE occurrence was 183 days (IQR 84 – 334) after treatment initiation. Resistance profile was the only predictor associated with occurrence of a SAEs. There was increased hazard of SAEs among patients with XDR-TB (adjusted HR=2.18, 95% CI: 1.12–4.23). Our findings on SAEs among patients treated with new or repurposed anti-TB drugs are echoing the findings available in the literature. They highlight the need for close monitoring of patients and underlines the importance of the aDSM during the whole treatment. Safety profile of the medications and combinations used are yet to be established and larger datasets comprised of patients receiving same treatment regimens need to be utilized.

Tailoring antituberculosis treatment regimen in a patient with serious adverse drug reactions to multiple drugs

Stevens–Johnson syndrome (SJS) and hepatitis are serious adverse drug reactions following the administration of anti-tuberculosis treatment (ATT). Here, we report a case of a young woman who developed hepatitis and SJS following ATT. Identifying the culprit drug and tailoring the appropriate regimen is a challenge to the clinicians. We described the clinical features, laboratory findings, hospital course and follow-up in a young female with tuberculosis, SJS and hepatitis in the case report. After the resolution of hepatitis, we confirmed the diagnosis of extrapulmonary tuberculosis and treated her after a cautious rechallenge with antitubercular drugs.

Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis.

Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis.

Isoniazid-Induced Systemic Lupus Erythematosus: A Case Report.

Systemic lupus erythematosus (SLE) can be induced by various medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, and minocycline. A patient was admitted complaining of fever with chills and rigor. After being diagnosed with tuberculous meningitis, the patient was given antituberculosis treatment. As the patient did not improve, detailed investigations were conducted, and elevated antinuclear antibody levels were found. The consulting physician diagnosed that the patient was suffering from SLE. As isoniazid is associated with an increased risk of developing SLE, it was suspected as the culprit drug. After withdrawing isoniazid from the antituberculosis treatment regimen, the patient improved and was discharged. Based on the WHO-UMC and Naranjo’s causality assessment criteria, an association between the reaction and isoniazid was deemed probable. The reaction was moderately severe (level 4b) according to the modified Hartwig and Siegel scale.

A Rare Etiology of Drug Rash in a Patient Receiving Anti-Tuberculosis Treatment

Anti-tuberculosis medications can cause various side effects, including drug rash. When a patient on anti-tuberculosis treatment (ATT) develops rash, we usually stop all medicines, rechallenge the patient with medications individually, and find the offending agent. It should be mentioned that drug rash can be also a manifestation of other diseases. Herein, we report a case of tuberculosis who developed rash while on ATT regimen but was later diagnosed to be concomitantly suffering from leprosy.