Clinical insights into tuberculosis otitis media: diagnosis, treatment, and management outcomes.

OBJECTIVES: The diagnosis of tuberculosis otitis media (TBOM) remains a great challenge. This study aims to suggest potential diagnostic clues and proper management of TBOM. METHODS: The study is a retrospective review of TBOM cases that were treated at our department, between January 2015 and June 2023. Summarizing their clinical characteristics, diagnosis, and treatment. Additionally, a literature review is conducted. RESULTS: Eight cases of TBOM, 6 female and 2 male patients, median age was 32 years old, were included in the study. TBOM mainly presents with symptoms of otorrhea, hearing loss, and occasional early-onset facial palsy. One case had a positive Purified Protein Derivative (PPD) before the operation. Middle ear tissue was pathologically biopsied in 7 cases, with 3 cases testing positive for Acid Fast Bacillus and 6 cases testing positive for Mycobacterium tuberculosis PCR. Middle ear surgery and Anti-tubercular treatment (ATT) were completed in all cases. The median follow-up was 11 months. No cases of TB relapse were observed. CONCLUSIONS: Proper suspicion and confirmation of TBOM is the primary clinical orientation. Middle ear surgery combination with ATT results in satisfactory outcomes. Hearing reconstruction should be performed after ATT is completed.

Implant-associated Mycobacterium tuberculosis infection (IMTI) in long-term, well-fixed implants.

Background: Orthopedic device infections caused by Mycobacterium tuberculosis, including Periprosthetic joint infection (PJI), are rare and peculiar due to its poor adherence to implant surface and weak ability of biofilm formation. We present successful treatment of 2 cases of implant associated Mycobacterium tuberculosis infection (IMTI) by meticulous surgical debridement and long-term anti-tubercular chemotherapy with retention of implant. Case descriptions: Case 1 : A case of Culture-Negative PJI, 4 years after left total hip replacement (THR) caused by M. tuberculosis. The patient presented with acute onset (<7 days) low grade fever and development of discharging sinus from the site of left surgical scar mark. Case 2: A patient with Kuntscher nailing done for open fracture right femur 22 years ago presented to clinic with complaints of discharging sinus (<7 days) from the surgical scar mark on right side. Both patients had negative cultures on presentation and underwent meticulous debridement with implant retention. Intra-operative samples were positive for M. tuberculosis on CB-NAAT and histopathology. They underwent successful treatment with 18 months of Anti Tubercular Treatment (ATT) without any relapse at 2 year-follow-up. Conclusion: Atypical, late onset discharging sinus with negative cultures should raise suspicion of IMTI. Intra-operative deep tissue samples should be analyzed for CB-NAAT for M. tuberculosis and histopathological analysis in all these cases. Meticulous debridement with 18 months chemotherapy poses viable option for successful treatment of IMTI, allowing retention of prosthesis.

A Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome Manifestation in Tubercular Cervical Lymphadenopathy: A Case Report.

A severe adverse reaction linked to a variety of medications, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is typified by a severe mucocutaneous rash, eosinophilia, fever, lymphadenopathy, and widespread systemic involvement. A 30-year-old female patient presented with fever, facial flushing, and a maculopapular rash that had been persistent for seven days on the upper limb, chest, belly, and lower limbs. She also had a cough with breathlessness for seven days which had progressed over the last seven days and also a rise in temperature in the evening. As the patient was started on anti-tubercular treatment (ATT) based on an interferon-gamma release assay report with no constitutional symptoms, we decided to reconfirm the diagnosis. Ultrasonography of the neck showed cervical lymphadenopathy measuring 21x11 mm in the left cervical region at level IB. The patient was advised for cervical lymph node fine needle aspiration to be sent for cytology and cartridge-based nucleic acid amplification test (CBNAAT) to restart ATT. The patient is being followed up.

Paediatric Spina Ventosa: tuberculous dactylitis of the thumb can be a mislaid differential diagnosis - case report.

The authors report a rare case of pediatric tuberculous dactylitis of the thumb with flexor tendon involvement in a child with multiple failed treatment attempts. The patient was diagnosed, treated and the outcome of the one-year follow-up was excellent. Extra pulmonary tuberculosis frequently surprises clinicians with aberrant presentations, which may be missed during radiographic studies, if not considered in differential diagnosis amid its rare location in the appendicular skeleton. This has been highlighted in this rare case of a girl in her mid-childhood with a spindle-shaped swelling with discharging sinuses at the right thumb proximal phalanx. Scenarios mimicking similar presentations such as Enchondromatosis, Chronic pyogenic osteomyelitis, Brodie's abscess and Actinomycosis, can be misleading. Several researchers have proffered up such rare cases, but after the anti-tubercular therapy era, the incidence has been exceptionally reduced. Still, a high index of suspicion can be helpful to avoid missing the diagnosis.

Role of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and Gene Xpert.

BACKGROUND: Mediastinal tubercular lymphadenitis is form of extrapulmonary tuberculosis [EPTB]. Clinical presentations are non-specific and diagnosis remains great clinical challenge. Microbiological and or histopathological evidences need to be present in order make diagnosis secure before initiation of anti-tubercular therapy (ATT). Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) provides tissue samples and aids management of this difficult to diagnosed entity. Current study describe role of EUS-FNA and Gene Xpert (GXP) in mediastinal tubercular lymphadenitis. METHODS: Retrospective analysis of 72 patients with mediastinal lymphadenopathy who underwent EUS-FNA were carried out. Linear echoendoscope was used for evaluation mediastinum. EUS echo features of LNs were studied. Twenty two-G needle used was for aspiration tissue sample from pathologic lymph nodes (LNs). FNA samples were analysed by cytology, Acid-Fast Bacilli (AFB) staining and GXP study. All procedures were uneventful without any complications. RESULTS: Forty two patients were diagnosed as tuberculosis (TB) following first EUS-FNA setting. Six patients underwent repeat EUS-FNA procedure following which another 3 were diagnosed as TB while remaining 3 started on empirical ATT based on additional supportive evidences. Forty five patients showed granulomatous inflammation on cytological analysis, AFB positivity noted in 16 (33.33%) patients while GXP in 26 (57.78%) patients. Rifampicin resistance detected in 3 ((6.25%) patients. All patients were followed clinico-radiologically for response to treatment. CONCLUSION: Tuberculous lymphadenitis is the most common cause of mediastinal lymphadenopathy in TB endemic countries. EUS-FNA provides microbiological and histopathological/cytological evidences in this difficult to diagnosed EPTB and thereby avoids empirical ATT.

Comprehensive Case Analysis of Tuberculous Meningitis in an Immunocompetent Patient: Diagnostic Challenges and Therapeutic Strategies.

Tuberculosis (TB) continues to be a significant global health concern, with India contributing substantially to the global burden. The management of TB is further complicated by HIV-associated immunodeficiency and the emergence of drug-resistant TB strains. Early diagnosis and treatment are critical, particularly for tubercular meningitis (TBM), which is among the most severe forms of extrapulmonary TB. We present the case of a 55-year-old male who arrived at our emergency department with a one-week history of fever, headache, incoherent speech, and slurred speech. The patient had no relevant medical history or known contact with TB patients. Neurological examination revealed ptosis of the right eye and a left extensor plantar response. Laboratory investigations revealed a miliary pattern on chest radiography, and cerebrospinal fluid analysis showed an adenosine deaminase (ADA) level of 14.4 U/L, a total cell count of 110/mm³, glucose of 6 mg/dL, and protein of 228.4 mg/dL, supporting the diagnosis of TBM. Magnetic resonance imaging (MRI) indicated brain lesions consistent with TBM. TBM represents the most devastating form of extrapulmonary TB if left untreated. Therefore, prompt initiation of antitubercular therapy and continued vigilance in endemic regions are essential for addressing this complex global health issue.

Ethambutol-Induced Optic Neuritis and Vision Loss: A Case Report.

Ethambutol is a first-line chemotherapeutic agent, which is commonly used in combination with other drugs for the treatment of tuberculosis. Ethambutol-induced optic neuritis is a serious and rare side effect that is either dose or duration-related and causes progressive painless vision loss, and cecocentral scotomas in the visual field. A rare case of ethambutol-induced optic neuritis was reported in a 52-year-old female who was taking anti-tubercular treatment for pulmonary tuberculosis for five months. She presented with painless diminished vision in both eyes. The patient was diagnosed with a rare case of optic neuritis through various examination methods. Ethambutol was stopped and therapy was continued with oral prednisone, zinc, and vitamin B complex being started along with anti-TB treatment. She showed no marked improvement in visual parameters until the last follow-up. The patient died due to cardiopulmonary arrest as a consequence of pulmonary tuberculosis.

A Case Report of Navigating Dual Respiratory Challenges: From Pulmonary Tuberculosis (PTB) to Allergic Bronchopulmonary Aspergillosis (ABPA).

This case study describes a unique scenario in which allergic bronchopulmonary aspergillosis (ABPA) was identified following treatment for pulmonary tuberculosis (PTB). ABPA is a complex pulmonary disorder that is often overlooked due to its nonspecific clinical presentation, especially in individuals concurrently diagnosed with tuberculosis (TB). Despite initial TB diagnosis and treatment, a 28-year-old male continued to experience respiratory symptoms, prompting further investigation that revealed underlying ABPA. This case underscores the importance of emphasizing the critical role of maintaining a high level of suspicion for ABPA in TB patients with persistent symptoms, highlighting the need for timely recognition and management to minimize further lung damage and improve patient outcomes.

Atypical Presentation of Primary Greater Trochanter Tuberculosis - A Case Report.

Introduction: Tuberculosis (TB) of the greater trochanter constitutes about 2% of musculoskeletal TB cases, often presenting with non-specific symptoms of localized pain, tenderness, and swelling, necessitating differentiation from other conditions like tumors. Bursal involvement results in the formation of a fluctuating mass. This case emphasizes the need for meticulous diagnostic evaluation in these cases due to their uncommon presentation and potential for inadequate assessment. Case Report: A 50-year-old male experienced hip pain and swelling after a trivial fall, leading to surgery for suspected abscess. Despite initial treatment, symptoms persisted which on further imaging suggested TB osteomyelitis that was confirmed on biopsy, prompting 18 months of anti-tubercular therapy. The patient showed significant improvement after a year, highlighting the importance of thorough evaluation and appropriate management in such cases. Conclusion: This case emphasizes the rare occurrence of primary TB in the greater trochanter, advocating for precise diagnosis through advanced imaging. It also underscores the importance of comprehensive TB testing, particularly in extrapulmonary cases which are prevalent in developing nations, to improve treatment outcomes.

Paradoxical Reaction in Intraocular Tuberculosis: Report of Three Cases.

PURPOSE: To present paradoxical reaction (PR) in three cases with ocular tuberculosis (OTB) treated with antitubercular therapy (ATT), highlighting diagnostic challenges and treatment strategies. METHODS: We retrospectively reviewed clinical records of three OTB patients presenting with paradoxical worsening after ATT initiation at two Brazilian university hospitals. RESULTS: The patients (2 males, 1 female) experienced worsening clinical presentation (increased inflammation, vision loss) within two to three weeks after initiating ATT. One patient who was HIV-positive with unilateral multifocal choroiditis developed PR soon after starting antiretroviral therapy. The second patient presented with a choroidal tuberculoma in both eyes. The third patient also had multifocal choroiditis and developed a localized choroidal elevation with a double-layer sign as a manifestation of PR. All patients were maintained on ATT therapy in association with corticosteroids and experienced improvement of inflammatory signs. CONCLUSION: This case series highlights the potential for PR in OTB patients. Close monitoring and prompt therapeutic adjustments are crucial for management success.

Report of renal allograft tuberculosis a decade after transplant: challenges in diagnosis and management.

Post-transplant infections constitute an important cause of morbidity and mortality in renal transplant recipients worldwide. Tuberculosis (TB) contributes significantly to this burden in endemic countries, such as India. We report a case of renal allograft TB, 10 years post-transplantation, diagnosed during a routine outpatient visit. An asymptomatic rise in serum creatinine level and a 6 month history of immunosuppressive drug non-compliance prompted evaluation of graft dysfunction. Biopsy of the renal allograft tissue suggested chronic active antibody mediated rejection with epithelioid granulomas in the interstitium. Guided by kidney biopsy, further testing with urine acid fast bacilli and urinary GeneXpert yielded positive results for TB. Treatment of TB was further complicated by the development of anti-tubercular therapy induced hepatitis and immune reconstitution inflammatory syndrome, which were managed with the reintroduction regimen and escalation of steroid dose, respectively. Our case highlights the atypical presentation and challenges in managing patients with TB in a post-renal transplant setting.

Recent Biochemical Advances in Antitubercular Drugs: Challenges and Future.

Tuberculosis (TB) is one of the leading causes of death world-wide after AIDS. It infects around one-third of global population and approximately two million people die annually from this disease because it is a very contagious disease spread by Mycobacterium tuberculosis. The increasing number of drug-resistant strains and the failure of conventional treatments against this strain are the challenges of the coming decades. New therapeutic techniques aim to confirm cure without deterioration, to reduce deaths, contagions and the formation of drug-resistant strains. A plethora of new diagnostic tests are available to diagnose the active tuberculosis, screen latent M. tuberculosis infection, and to identify drug-resistant strains of M. tuberculosis. When effective prevention strategies do not prevail, high rates of early case detection and successive cures to control TB emergence would not be possible. In this review, we discussed the structural features of M. tuberculosis, Multi drug resistance tuberculosis (MDR-TB), extremely drug-resistant tuberculosis (XDR-TB), the mechanism of M. tuberculosis infection, the mode of action of first and second-line antitubercular drugs, the mechanism of resistance to the existing drugs, compounds in preclinical and clinical trial and drugs presently available for the treatment of tuberculosis. Moreover, the new diagnostic techniques to detect M. Tuberculosis are also discussed in this review.

Isolated Pyomyositis of the Thigh With a Sinus Tract: A Rare Presentation of Tuberculosis.

Muscular tuberculosis as a primary focal lesion in an immunocompetent individual without any underlying bone involvement is a rare finding. The authors present a case of a young female in her 30s who presented with complaints of recurrent discharging sinus in the posteromedial aspect of the proximal right thigh for eight months. The patient was treated by surgical debridement followed by antitubercular therapy (ATT) and has shown full recovery during the post-eight-month treatment period. Such a presentation of primary tubercular pyomyositis imposes a diagnostic as well as a therapeutic challenge.

NMI-SO2Cl2-Mediated Amide Bond Formation: Facile Synthesis of Some Dihydrotriazolopyrimidine Amide Derivatives as Potential Anti-Inflammatory and Anti-Tubercular Agents.

Facile access to some novel biologically relevant dihydrotriazolopyrimidine carboxylic acid-derived amide analogues using NMI/SO2Cl2, and aromatic and aliphatic primary and secondary amines, is reported herein. The role of N-methylimidazole (NMI) as the base and sulfuryl chloride (SO2Cl2) as the coupling reagent has been effectively realized in accessing these molecules in good to excellent yields. The feasibility of the developed protocol has also been extended to the gram-scale synthesis of N-benzylbenzamide in a 75% yield from benzoic acid and benzyl amine. The newly synthesized compounds were tested via in vitro anti-inflammatory and anti-tubercular activity studies. The compounds 6aa and 6be were found to be the most active anti-inflammatory agents, whereas 6cb and 6ch were found to exhibit promising anti-tubercular potency when compared to other synthesized molecules. The structure-activity relationship (SAR) studies revealed the importance of the presence of electron-donating functionalities in enhancing the anti-inflammatory potential of the newly synthesized molecules. However, the presence of electron-withdrawing substituents was found to be significant for improving their anti-tubercular potency.

Pharmacokinetic-Pharmacodynamic (PK-PD) Analysis of Second-Line Anti-Tubercular Drugs in Indian Children with Multi-Drug Resistance.

OBJECTIVES: To conduct a thorough pharmacokinetic (PK) - pharmacodynamic (PD) analysis of second-line anti-tubercular therapy (ATT) in children diagnosed with multi-drug resistant tuberculosis (MDR-TB). METHODS: Twenty-seven children undergoing second-line ATT, including kanamycin (KM, n = 13), fluoroquinolones (FQs, n = 26), ethionamide (ETH, n = 20), para amino salicylic acid (PASA, n = 4), and cycloserine (CS, n = 15), were sampled at 0 (pre-dose), 1, 2, 3, and 4 h post-drug administration. Plasma drug levels were determined using a mass spectrometer and the collected dataset underwent non-compartmental PK analysis using PK solver ver2.0. PK/PD assessments involved individual drug simulation studies on 1000 subjects using Modviz Pop ver 1.0 in R-software. RESULTS: A total of 22 and 5 children were considered as responders and non-responders, respectively. Non-compartmental PK analysis revealed mean plasma drug levels of this study cohort attained the targeted maximum drug plasma concentration (Cmax). The ratio of Cmax /minimum inhibitory concentration (MIC) or the area under the curve (AUC)/MIC of the studied drugs had not shown a significant difference between responders and non-responders. Non-responders of ETH and ofloxacin had shown deviation from the derived dose-response profile for the simulated population. CONCLUSIONS: The management of MDR-TB with second-line ATT following national guidelines had cured the majority of the children (> 80%) who participated in the study. Inter-individual variability in few children from the targeted Cmax range suggests the need for future investigations on pharmacogenomic aspects of drug metabolism.

Evaluation of clinical profiles, imaging findings and antituberculosis treatment outcome in granulomatous mastitis: An Indian scenario.

BACKGROUND: The management of choice for granulomatous mastitis (GM) has yet to be determined but few studies have demonstrated that anti-tubercular treatment (ATT) could be an effective alternative therapeutic option. Hence, the objective of the current study is to determine the clinical feature, radiological imaging findings, and histopathological examination results exhibited by GM and tuberculosis (TB)-proven GM as well as to evaluate the ATT clinical outcome in GM patients. METHODS: The study was performed on 68 GM patients who were referred to the department of pulmonology by the breast clinic (from January 2018 to August 2021). Study populations were categorized into two groups GM and TB-proven GM patients and all were prescribed with standard ATT regimen and were continuously followed up. SPSS version 25 was employed for statistical assessment. RESULTS: Our study showed that 6 patients from GM and 4 patients from the TB-proven GM group got relapsed. For patients who displayed partial remission, ATT treatment was started after assessing the side effects potential. 14.6% (n = 6) and 7.4% (n = 2) patients who initially demonstrated partial remission were also completely cured. ATT treatment curable rate was determined to be 90% (n = 37) and 81.5% (n = 22) for GM and TB-proven GM patients correspondingly. Therefore, the current study demonstrated nil significant differences between groups. CONCLUSION: The current study warrants that ATT therapy could be an effective and better treatment of choice for GM patients irrespective of their clinical condition.

Anti-Tubercular-Therapy-Induced Severe Thrombocytopenia Presenting as a Vocal Cord Bleed With Massive Hemoptysis Causing Mortality: A Catastrophic Combination.

Severe thrombocytopenia induced by anti-tubercular therapy (ATT) is a rare but potentially life-threatening complication. Severe thrombocytopenia is a known adverse effect of ATT, but its association with fatal hemoptysis is rare. Hematemesis and hemoptysis are two serious symptoms that indicate bleeding from the upper gastrointestinal and the lower respiratory tract, respectively. We report a rare case of a 65-year-old man, a diagnosed case of tuberculosis on ATT, who presented with massive hemoptysis. On navigating the bleed, the source was found to be a vocal cord bleed, which further led to massive clot formation in the left bronchus, leading to the collapse of the subsequent lung, leading to mortality. This case emphasizes the importance of recognizing ATT as a potential cause of bleeding and considering causes of massive hematemesis that are not gastrointestinal. It also highlights the need for a thorough evaluation of the airway in such patients.

Severe dengue infection unmasking drug-induced liver injury: Successful management with N-acetylcysteine.

Key Clinical Message: Clinicians in tuberculosis and dengue endemic regions should have heightened vigilance for drug-induced liver injury (DILI) overlapping with active infections, enabling prompt recognition and life-saving conservative management. Abstract: Severe dengue and drug-induced liver injury (DILI) are significant independent risk factors for acute liver failure. The co-occurrence of these conditions significantly complicates clinical management. Here, we describe the case of a 21-year-old Nepali female who developed acute liver failure during antitubercular therapy (ATT). The patient, presenting with fever and nausea after 3 weeks of ATT, subsequently received a diagnosis of severe dengue. Laboratory evidence indicated markedly elevated transaminases (AST 4335 U/L, ALT 1958 U/L), total bilirubin (72 µmol/L), and INR (>5). Prompt discontinuation of first-line ATT, initiation of a modified ATT regimen, and N-acetylcysteine (NAC) infusion facilitated the patient's recovery after a week of intensive care. This case underscores the potential for synergistic hepatotoxicity in regions where multiple endemic illnesses coincide. Early recognition of DILI, cessation of offending agents, and comprehensive intensive care are crucial interventions. While the definitive efficacy of NAC remains under investigation, its timely administration in these complex cases warrants exploration for its potential lifesaving benefits.

Mannose-Decorated Solid-Lipid Nanoparticles for Alveolar Macrophage Targeted Delivery of Rifampicin.

Alveolar macrophages play a vital role in a variety of lung diseases, including tuberculosis. Thus, alveolar macrophage targeted anti-tubercular drug delivery through nanocarriers could improve its therapeutic response against tuberculosis. The current study aimed at exploring the efficacy of glyceryl monostearate (GMS)-based solid-lipid nanoparticles (SLNs) and their mannose functionalized forms on the alveolar macrophage targeting ability of an anti-tubercular model drug, rifampicin (Rif). Rif-loaded SLNs were accomplished by the solvent diffusion method. These carriers with unimodal particle size distribution (~170 nm) were further surface-modified with mannose via Schiff-base reaction, leading to slight enhancement of particle diameter and a decline of drug loading capacity. The encapsulated Rif, which was molecularly dispersed within the matrices as indicated by their XRD patterns, was eluted in a sustained manner with an initial burst release effect. The uptake efficiency of mannose-modified SLNs was remarkably higher than that of corresponding native forms on murine macrophage Raw 264.7 cells and human lung adenocarcinoma A549 cells. Eventually, the mannose-modified SLNs showed a greater cytotoxicity on Raw 264.7 and A549 cells relative to their unmodified forms. Overall, our study demonstrated that mannose modification of SLNs had an influence on their uptake by alveolar macrophages, which could provide guidance for the future development of alveolar macrophage targeted nanoformulations.