Antituberculous Agents Research Articles

The recent outstanding medicinal activity of 2- (aryl/heteroaryl) thiazolidine-4-one derivatives as antituberculous agents

The recent outstanding medicinal activity of 2- (aryl/heteroaryl) thiazolidine-4-one derivatives as antituberculous agents

Thiadiazole and Thiazole Derivatives as Potential Antimicrobial Agents.

This review summarizes data on heterocyclic systems with thiadiazole and thiazole fragments in molecules as promising antimicrobial agents. Thiadiazole and thiazole backbones are the most favored and well-known heterocycles, a common and essential feature of various drugs. These scaffolds occupy a central position and are the main structural components of numerous drugs with a wide spectrum of action. These include antimicrobial, antituberculous, anti-inflammatory, analgesic, antiepileptic, antiviral, and anticancer agents. The research is based on bibliosemantic and analytical methods using bibliographic and abstract databases, as well as databases of chemical compounds. This review reports on thiadiazole and thiazole derivatives, which have important pharmacological properties. We are reviewing the structural modifications of various thiadiazole and thiazole derivatives, more specifically, the antimicrobial activity reported over the last years, as we have taken this as our main research area. 80 compounds were illustrated, and various derivatives containing hydrazone bridged thiazole and pyrrole rings, 2-pyridine and 4-pyridine substituted thiazole derivatives, compounds containing di-, tri- and tetrathiazole moieties, spiro-substituted 4- thiazolidinone-imidazoline-pyridines were analyzed. Derivatives of 5-heteroarylidene-2,4- thiazolidinediones, fluoroquinolone-thiadiazole hybrids, and others. 1,3,4-thiadiazoles and thiazoles are valuable resource for researchers engaged in rational drug design and development in this area.

Clinical manifestations and prognosis of tuberculous spondylitis in an adolescent with disseminated tuberculosis: a case report

Indonesia is one of the countries with the highest number of tuberculosis (TB) cases globally. Around 10-20% of adolescents with TB infection progress to pulmonary TB, and less than 0.5% develop miliary or central nervous system TB. TB spondylitis occurs in only 5.6% of extrapulmonary TB patients. The clinical manifestations of disseminated and TB spondylitis are heterogeneous and insidious, with several potential risk- and prognostic factors. We report the case of a 16-year-old male admitted with abdominal distension, paraplegia, and urinary retention. He was diagnosed with disseminated TB with TB spondylitis. This case was unique because the patient had no classic symptoms of pulmonary TB. This report focuses on the diagnosis, comprehensive management, and prognosis of TB spondylitis, as well as the risk factors for disseminated TB. The management consisted of antituberculous agents and surgery. The prognosis is influenced by the patient’s age, severity of kyphosis deformity, number of vertebrae involved, lesion site, and patient’s health status, including nutritional status.

Multi-drug resistant Mycobacterium abscessus septic arthritis following an intra-articular steroid injection; a case report

Background: Mycobacterium abscessus (M. abscessus), a rapidly growing Mycobacterium (RGM) is an emergent cause of soft issue and musculoskeletal infections. Treatment is often complicated by commonly occurring intrinsic and acquired resistance to not only the classical anti-tuberculous agents but also to most currently available antibiotics. Case Presentation: We present a case of left thumb carpometacarpal (CMC) joint septic arthritis in a 66-year-old American Caucasian woman following an intra-articular steroid injection for osteoarthritis treatment. She did not improve on conventional empirical cellulitis treatment prompting culture and sensitivity assays. Mycobacterium abscessus Deoxyribonucleic acid was detected by real-time polymerase chain reaction (PCR) with additional cultures growing the same organism within a week. Samples were sent to the New York State Department of Health for a full culture and sensitivity profile which demonstrated extensive resistance to antibacterial agents including conventional anti-tuberculous agents. Conclusion: This case not only highlights the importance of having a high degree of suspicion for M. abscessus in joint and soft tissue infections not improving to commonly used empirical therapies even in low prevalent areas. It also underlines the importance of performing cultures and sensitivity given antibiotic combinations for most RGM infections should be sensitivity guided.

More Tailored Approaches to Tuberculosis Treatment and Prevention.

Recent advances in the treatment of tuberculosis (TB) have led to improvements unprecedented in our lifetime. Decades of research in developing new drugs, especially for multidrug-resistant TB, have created not only multiple new antituberculous agents but also a new approach to development and treatment, with a focus on maximizing the benefit to the individual patient. Prevention of TB disease has also been improved and recognized as a critical component of global TB control. While the momentum is positive, it will take continued investment at all levels, especially training of new dedicated TB researchers and advocates around the world, to maintain this progress.

Evaluation of Anti-Inflammatory and Anti-Tubercular Activity of 4-Methyl-7-Substituted Coumarin Hybrids and Their Structure Activity Relationships.

Four sets of previously synthesized 4-methyl-7-substituted coumarin derivatives were screened for their in vitro anti-inflammatory and anti-tubercular activities. The anti-inflammatory potential of 3a-t, 5a-o, 6a-n, and 7a-f synthesized compounds was evaluated by an anti-denaturation assay using diclofenac sodium as the reference standard. Evaluation of the anti-tuberculous activity of the mentioned compounds was performed by the Resazurin test method against four different TB strains using rifampicin and isoniazid as reference drugs. Based on the anti-inflammatory results, compounds 3o, 5f, 6c, and 7d proved to be the most active compounds in their respective series. Additionally, compounds 3k-n, 5b-d, 6d-f, 6k, 7a, and 7f were found to be the most potent anti-tuberculous agents. In fact, most of the screened compounds exhibited promising activity profiles compared to the respective standard drugs. The structure-activity connections revealed a few intriguing aspects, indicating that the presence of electron-donating and nitrogen-rich fragments boost the anti-inflammatory effects of the examined compounds. However, the presence of electron-withdrawing substituents was required to boost the anti-tubercular activity of the evaluated compounds.

Peritoneal and pulmonary tuberculosis following intravesical administration of Bacillus Calmette-Guérin for bladder cancer.

We report a rare case of peritoneal and pulmonary tuberculosis after intravesical instillation of Bacillus Calmette-Guérin (BCG). A 76-year-old man diagnosed as high-grade urothelial carcinoma (UC) with carcinoma in situ (CIS) was treated with intravesical BCG instillation and transurethral resection of bladder tumor (TUR-BT). Three months later, TUR-BT for recurrent tumors and multiple site biopsy of bladder mucosa were performed. During TUR-BT, near perforation in the posterior wall was observed, and was disappeared after observation with urethral catheterization for 1 week. Two weeks later, he was admitted with a complaint of abdominal distention, and a computed tomography (CT) showed ascites. One week later, CT showed pleural effusion and worsening of ascites. Drainage of pleural effusion and ascites puncture was performed, and elevated adenosine deaminase (ADA) and lymphocytes count were subsequently found. In laparoscopic examination, numerous white nodules were observed in the peritoneum and omentum, and Langhans giant cells were pathologically identified in biopsy specimens. Mycobacterium culture confirmed Mycobacterium tuberculosis complex. The patient was then diagnosed with pulmonary and peritoneal tuberculosis. Anti-tuberculous agents consisting of isoniazid (INH), rifampicin (RFP), and ethambutol (EB) were administered. Six months later, a CT scan showed no evidence of pleural effusion or ascites. There has been no recurrence of either urothelial cancer or tuberculosis during follow-up for 2 years.

Tuberculosis of the breast neoplastic-like about two report cases: A rare often unrecognized diagnosis.

Tuberculosis of the breast is a very rare infection; it occurs chiefly in women of childbearing potential, usually as an apparently primary infection and constitutes a diagnosis and therapeutic challenge. Administration of antituberculous agents is the mainstay of therapy. Surgery is required in some cases.We report tow cases of breast tuberculosis. The diagnosis has been established on histology. Outcome was favorable under anti bacillary treatment.Through the literature data we recall the epidemiological, clinical, diagnostic and treatment of this pathology.

Desensitization for the prevention of drug hypersensitivity reactions.

Drug desensitization is the temporary induction of tolerance to a sensitized drug by administering slow increments of the drug, starting from a very small amount to a full therapeutic dose. It can be used as a therapeutic strategy for patients with drug hypersensitivity when no comparable alternatives are available. Desensitization has been recommended for immunoglobulin E (IgE)-mediated immediate hypersensitivity; however, its indications have recently been expanded to include non-IgE-mediated, non-immunological, or delayed T cell-mediated reactions. Currently, the mechanism of desensitization is not fully understood. However, the attenuation of various intracellular signals in target cells is an area of active research, such as high-affinity IgE receptor (FcɛRI) internalization, anti-drug IgG4 blocking antibody, altered signaling pathways in mast cells and basophils, and reduced Ca2+ influx. Agents commonly requiring desensitization include antineoplastic agents, antibiotics, antituberculous agents, and aspirin/nonsteroidal antiinflammatory drugs. Various desensitization protocols (rapid or slow, multi-bag or one-bag, with different target doses) have been proposed for each drug. An appropriate protocol should be selected with the appropriate concentration, dosage, dosing interval, and route of administration. In addition, the protocol should be adjusted with consideration of the severity of the initial reaction, the characteristics of the drug itself, as well as the frequency, pattern, and degree of breakthrough reactions.

Emerging therapeutic drug monitoring of anti-infective agents in Australian hospitals: Availability, performance and barriers to implementation.

The purpose of the study was to assess the status of emerging therapeutic drug monitoring (TDM) of anti-infective agents in Australian hospitals. A nationwide cross-sectional survey of all Australian hospitals operating in the public and private health sector was conducted between August and September 2019. The survey consisted of questions regarding institutional TDM practice for anti-infective agents and clinical vignettes specific to β-lactam antibiotics. Responses were received from 82 unique institutions, representing all Australian states and territories. All 29 (100%) of principal referral (major) hospitals in Australia participated. Five surveys were partially complete. Only 25% (20/80) of hospitals had TDM testing available on-site for any of the eight emerging TDM candidates considered: β-lactam antibiotics, anti-tuberculous agents, flucytosine, fluoroquinolones, ganciclovir, human immunodeficiency virus (HIV) drugs, linezolid and teicoplanin. A considerable time lag was noted between TDM sampling and reporting of results. With respect to β-lactam antibiotic TDM, variable indications, pharmacodynamic targets and sampling times were identified. The three greatest barriers to local TDM performance were found to be (1) lack of timely assays/results, (2) lack of institutional-wide expertise and/or training and (3) lack of guidelines to inform ordering of TDM and interpretation of results. The majority of respondents favoured establishing national TDM guidelines and increasing access to dose prediction software, at rates of 89% and 96%, respectively. Translating emerging TDM evidence into daily clinical practice is slow. Concerted efforts are required to address the barriers identified and facilitate the implementation of standardised practice.

Quinoxaline 1,4-di-N-oxides: a review of the importance of their structure in the development of drugs against infectious diseases and cancer

Quinoxaline 1,4-di-N-oxides (QdNO’s) are potent drugs used since the middle of the last century as food additives to improve animal growth; however, their use as antibacterial agents led to an interest in investigating their mechanism of action, discovering that this heterocycle can cause DNA damage. Consequently, many molecules with different applications have been developed, with most of the research focused on studying their action as antibiotics, antifungals, antiparasitics, antituberculous, and anticancer agents. This review aims to present a condensate of the leading QdNO’s derivatives, as well as a description of the biological activities finding the importance of the nature and type of substituents present in positions R2, R3, R6, and R7 when they are biologically evaluated.

Multicentre testing of the EUCAST broth microdilution reference method for MIC determination on Mycobacterium tuberculosis

ObjectivesThe first objective of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) subcommittee for antimycobacterial susceptibility testing (AMST), launched in 2016, was to set a reference method for determining the MICs of antituberculous agents, since many protocols are used worldwide and a consensus one is needed for the determination of microbiological breakpoints. MethodsDuring 2017 and 2018, MIC determination protocols were evaluated prospectively in a multicentre study within the four AMST laboratories. MIC results were obtained for isoniazid, levofloxacin and amikacin on the reference strain Mycobacterium tuberculosis H37Rv ATCC 27294. Broth microdilution (BMD) in Middlebrook 7H9 and solid medium dilution (SMD) in Middlebrook 7H10 were performed using two inoculum concentrations. MICs were interpreted with regard to visual and 99% inhibition after 7, 14 or 21 days of incubation for BMD and 21 days for SMD. ResultsFollowing the EUCAST reference protocol, intra- and inter-assay agreements were within ±1 MIC dilution for >95% of the observations for the three drugs in both methods. MIC values, presented as MIC mode (range) for BMD and SMD respectively, were: 0.03 (0.015–0.06) mg/L and 0.12 (0.06–0.25) mg/L for isoniazid, 0.25 mg/L (0.25–0.5) and 0.5 mg/L (0.12–0.5) for levofloxacin, and 0.5 mg/L (0.5–1.0) and 0.5 mg/L (0.5–1.0) for amikacin. ConclusionsBoth SMD and BMD were reproducible and eligible as a reference method for MIC determination of the Mycobacterium tuberculosis complex (MTBC). BMD was finally selected as the EUCAST reference method. From now on it will be used to set epidemiological cut-off values and clinical breakpoints of new and old antituberculous agents.

A Nationwide Study of Severe Cutaneous Adverse Reactions Based on the Multicenter Registry in Korea

Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur,clinical data based on large-scale studies are still lacking. To provide information on culprit drugs and clinical characteristics, including morbidity and mortality of SCARs based on a nationwide registry. SCAR cases that occurred from 2010 to 2015 were recruited to the Korean SCAR registry from 34 tertiary referral hospitals. Demographics, causative drugs, causality, and clinical outcomes were collected by reviewing the medical record. A total of 745 SCAR cases (384 SJS/TEN cases and 361 DRESS cases) due to 149 drugs were registered. The main causative drugs were allopurinol (14.0%), carbamazepine (9.5%), vancomycin (4.7%), and antituberculous agents (6.3%). A strong preference for SJS/TEN was observed in carbonic anhydrase inhibitors (100%), nonsteroidal anti-inflammatory drugs (84%), and acetaminophen (83%), whereas dapsone (100%), antituberculous agents (81%), and glycopeptide antibacterials (78%) were more likely to cause DRESS. The mortality rate was 6.6% (SJS/TEN 8.9% and DRESS 4.2%). The median time to death was 19 days and 29 days in SJS/TEN and DRESS respectively, and 89.8% of deaths occurred within 60 days after the onset of the skin symptoms. Allopurinol, carbamazepine, vancomycin, and antituberculous agents were the leading causes of SCARs in Korea. Some drugs preferentially caused a specific phenotype. The mortality rate of SCARs was 6.6%, and most of the deaths occurred within 2 months.

Antimicrobial susceptibility testing of Mycobacterium tuberculosis complex isolates – the EUCAST broth microdilution reference method for MIC determination

ScopeSeveral methods are used worldwide for antibiotic susceptibility testing (AST) for the Mycobacterium tuberculosis complex (MTBC). The variability in the results obtained with these methods hampers setting epidemiological cut-off (ECOFF) values and clinical breakpoints according to EUCAST guidelines. Methods for susceptibility testing and determination of the minimal inhibitory concentrations (MICs) need to be standardized for MTBC isolates for old and new agents. Our objective was to establish a standardized reference method for MIC determination for MTBC. MethodsThe EUCAST antimycobacterial susceptibility testing subcommittee (AMST) compared protocols of MIC determination with regard to medium, inoculum preparation, antituberculous agent preparation, incubation, reading of the results and interpretation. RecommendationsThe EUCAST reference method of MIC determination for MTBC is the broth microdilution method in Middlebrook 7H9-10% OADC medium. The final inoculum is a 105 CFU/mL suspension, obtained from a 10−2 dilution of a 0.5 McFarland suspension prepared after vortexing bacterial colonies with glass beads before suspending them in sterile water. The culture is maintained in a U-shaped 96-well polystyrene microtitre sterile plate with a lid incubated at 36° ± 1°C. Reading is done using an inverted mirror as soon as the 1:100 diluted control (i.e. 103 CFU/mL suspension) shows visual growth. The MIC, expressed in mg/L, is the lowest concentration that inhibits visual growth. Mycobacterium tuberculosis H37Rv ATCC 27294 is used as the reference strain and its targeted MIC values are within the range 0.03–0.12 for isoniazid, 0.12–0.5 for levofloxacin and 0.25–1 mg/L for amikacin. ConclusionsThe EUCAST reference method for MTBC was endorsed by EUCAST after public consultation and will from now on be used to define EUCAST ECOFFs and clinical breakpoints. This reference method is not primarily intended to be used under routine conditions and the AST methods will need to be calibrated against this reference method to be used with EUCAST breakpoints.

MON-482 Thyroid Tuberculosis - An Unlikely Diagnosis

Background: Mycobacterium tuberculosis (MTB) is an aerobic bacillus responsible for the most cases of tuberculous infection. Approximately one-third of the world’s population is infected. Tuberculosis (TB) of the thyroid gland is an unusual diagnosis with an estimated prevalence of 0.1 to 0.6%. The thyroid TB can mimic different pathologies (thyroid neoplasms, lymphoma, infectious or granulomatous thyroiditis, Graves’ disease or bacterial abscess) and the diagnosis can be easily disregarded, especially in non-endemic countries and if the patient doesn’t have systemic symptoms. The fine needle aspiration and histopathological examination, with acid-fast bacilli staining and TB culture, are the gold standard exams.Clinical Case: A 71-year-old female was referred to our Endocrinology department after a diagnosis of nodular thyroid disease. She had complaints of slight cervical discomfort, with 6 months of duration. She hadn’t personal or familiar relevant antecedents. At observation, a movable, elastic and non-tender nodule of 15mm at the right superior thyroid lobe was identified. Blood tests including a thyroid profile were normal. The neck ultrasound showed, at the right lobe of the thyroid, multiple solid nodules; the dominant had 18mm, was heterogeneous and had multiple calcifications. Moreover, lymph nodes with suspicious ultrasonographic features along the right internal jugular chain were reported. The patient underwent fine-needle aspiration (FNA) of the suspicious thyroid nodule and one lymph node. Results were respectively: non-diagnostic (Bethesda I) and reactive pattern. FNA was repeated on a different occasion and results were similar. Due to ultrasound suspicious of malignancy, a total thyroidectomy was performed and a lymph node from level IV was sampled for extemporaneous examination. Necrotizing granulomas were documented; the Ziehl-Neelson staining (ZNS) was negative; material was sent to microbiology. Following this finding, ganglion emptying was not performed. The thyroid histology showed tuberculoid type granulomas with lymphoid border and central necrosis. However, the ZNS was negative. The diagnosis was definitely established by a positive culture of the lymph node tissue and molecular detection, by polymerase chain reaction (PCR), of MTB. Pulmonary involvement was excluded and she started antituberculous agents planned for 9 months (rifampicin and isoniazid during 9 months and ethambutol and pyrazinamide for 2 months).Conclusion: Thyroid TB is a rare presentation of extrapulmonary tuberculosis. In presence of systemic or specific complaints or history of exposition the diagnosis may be suspected and confirmatory tests requested in order to ensure an adequate treatment. However, sometimes, histopathology remains a key step and the use of cultures improves the sensitivity and specificity of TB tests.

P875 A suspected case of extra-pulmonary tuberculosis presenting as effusive-constrictive pericarditis

Abstract Case presentation A 33 year-old black female, born in Angola, staying in Portugal 1 week before admission presented to the emergency department of our hospital with a history of worsening but recurring pleuritic chest accompanied by dyspnea, fatigue, peripheral oedema and sweating in the past 4 years. Initial workup in Angola and more recently in Namibia was unrevealing. The patient had taken 3 months of antituberculous agents and a systemic corticosteroid and was medicated with furosemide and spironolactone. Since then the symptoms persisted and multiple admissions for decompensated heart failure followed. At presentation median blood pressure was 60mmHg, heart rate 90 beats per minute, temperature 37,6ºC. Auscultation had signs of pulmonary congestion and muffled heart sounds, the neck veins were distended. An electrocardiogram showed sinus rhythm and low-voltage complexes in limb and precordial leads. Initial transthoracic echocardiogram revealed a thickened pericardium with circunferencial effusion and marked respiratory variation (>25%) of the mitral and tricuspid inflow doppler velocities. Pericardiocentesis was performed with improved dyspnea and blood pressure after drainage of 650 mL of serohematic fluid. Echocardiographic follow-up showed a mild circunferencial pericardial effusion and extensive areas of thickened crypted pericardium with fibrin strands containing heterogeneous fluid (figure 1). There were signs of constriction. A cardiac CT revealed no calcium deposition. Fluid cytology was predominant for lymphocytes and biochemistry, cultures, polymerase chain reaction and immunochemistry were inconclusive and no pathologic agent was isolated. The image findings in the transthoracic echocardiogram coupled with the demographics and past clinical history of the patient prompt the initiation of antituberculous therapy in association with systemic corticosteroids in an attempt to ameliorate the pericardial constriction. Despite initial therapeutic response, constriction was deemed irreversible and pericardiectomy was performed. The workup for definitive diagnosis is still undergoing. Discussion Effusive-constrictive pericarditis is defined by a pericardial effusion with signs of concurrent pericardial constriction. In these cases the scarred pericardium not only constricts cardiac volume but can also accommodate pericardial fluid under increased pressure leading to signs of cardiac tamponade. The initial approach should be the treatment of the underlying condition but if such remains ineffective, pericardiectomy is the remaining option and is reserved for patients in which constriction becomes severe and/or persistent. This condition is more prevalent with tuberculous pericarditis and when suspected presumptive treatment should be initiated in immunocompetent patients from endemic regions. Antituberculous treatment regimens in conjunction with systemic corticosteroids have shown to prevent complications from pericardial constriction. Abstract P875 Figure.

TB OR NOT TB: A CASE OF NONTB MYCOBACTERIAL LUNG DISEASE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Nontuberculous mycobacteria (NTM) are naturally-occurring organisms found in water and soil. NTM lung infection occurs when a person inhales the organism from their environment. Most people do not become ill but some susceptible individuals develop progressive and destructive lung disease. CASE PRESENTATION: 80-year-old female with a past medical history of emphysema presented with complaints of malaise and fatigue for 3-4 months. She also complained of dry cough, shortness of breath, hoarseness of voice and right upper chest wall discomfort. She was a non-smoker and retired nurse by profession. Physical exam was notable for a thin, frail build, supraclavicular hollowing, along with increased vocal fremitus and vocal resonance in the right upper lung fields. Further history revealed that she had secondhand smoke exposure from her husband years ago as well as a history of suspected Tuberculosis when she was young. Chest X-Ray and follow up CT scan revealed a 7 cm cavity in her right upper lobe. Her vitals and labs were within normal limits and her Sputum Acid Fast Bacilli smear x 3 was negative. Sputum cultures grew out mycobacteria 6 weeks later. Rapid speciation via Mass spectrometry revealed Mycobacterium abscessus. The patient was started on a long course of a triple-drug regimen of parenteral Amikacin and Imipenem along with oral Clarithromycin for treatment. DISCUSSION: M. abscessus is 1 of the 3 clinically relevant species among Nontuberculous mycobacteria. It is the third most frequently recovered nontuberculous mycobacteria in the US and accounts for 80% of the rapidly growing mycobacteria respiratory disease isolates. The demographic affected by M. abscessus generally include white nonsmoking females over the age of 60 with no predisposing lung conditions and those who were less than 50 years of age usually had a recognized underlying lung disease. There are clinical and microbiological criteria required for diagnosing nontuberculous mycobacterial lung disease, and it is a diagnosis of exclusion. M. abscessus are uniformly resistant to the standard anti-tuberculous agents. As per current guidelines, the only predictable curative therapy for limited (focal) lung disease is surgical resection combined with multidrug therapy, including a macrolide and one or more parenteral agents over several months to help control symptoms and progression. The major drawback of therapy stems from the adverse drug reactions associated with long-term use of parenteral agents. CONCLUSIONS: In the United States, the incidence of nontuberculous mycobacterial lung disease is rising, particularly among the elder age groups and hence must be considered in the differential diagnosis once more common etiologies have been excluded. Unfortunately, at present there are recommendations but there is no reliable and dependable antibiotic regimen to produce a cure for extensive Mycobacterium abscessus lung disease. Reference #1: Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175:367–416. DOIPubMed Reference #2: Pillai SK, Beekmann SE, Santibanez S, Polgreen PM. The Infectious Diseases Society of America Emerging Infections Network: bridging the gap between clinical infectious diseases and public health.Clin Infect Dis. 2014;58:991–6. DOIPubMed Reference #3: Lyu J, Jang HJ, Song JW, Choi CM, Oh YM, Lee SD, Outcomes in patients with Mycobacterium abscessus pulmonary disease treated with long-term injectable drugs. Respir Med. 2011;105:781–7.DOIPubMed DISCLOSURES: No relevant relationships by Sneha Lakshman, source=Web Response

Reactions to Antituberculous Drugs and Desensitization Treatment

This paper intends to review the most frequent adverse reactions to antituberculous drugs specifically those classified as hypersensitivity in nature, and how to deal with this problem in practical terms. It is known that any adverse effect can occur with any drug and antituberculous agents are not an exception. Some risk factors have been described including high age, malnutrition, and high alcohol consumption. We will focus on hypersensitivity reactions to isoniazid, rifampicin, pyrazinamide, and ethambutol. The paper addresses specifically the most described hypersensitivity reactions to each of these drugs. If any important reaction occurs, the drugs should be stopped until total resolution of the reaction. When other strategies fail and if the drug is necessary as one of the first-line drugs to the treatment, desensitization can be used as a method to o reintroduce the drug. The authors address this issue either in theoretical terms as examples with protocols for immediate and non-immediate reactions.

4-(Het)aryl-4,7-dihydroazolopyrimidines and Their Tuberculostatic Activity

Structural analogs of a promising antituberculous agent, ethyl 5-methyl-7-(thiophen-2-yl)-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate have been synthesized by three-component condensations of various aromatic or hetaromatic aldehydes with several β-dicarbonyl compounds (CH acids) and 1H-1,2,4-triazol-5-amine or 1H-pyrazol-5-amine. The obtained compounds have been evaluated for tuberculostatic activity, and structure-activity relations have been analyzed.

A qualitative evaluation of hospital versus community-based management of patients on injectable treatments for tuberculosis

BackgroundPatients being treated for recurrent or multidrug-resistant tuberculosis (TB) require long courses of injectable anti-tuberculous agents. In order to maintain strong TB control programmes, it is vital that the experiences of people who receive long-term injectables for TB are well understood. To investigate the feasibility of a novel model of care delivery, a clinical trial (The TB-RROC Study) was conducted at two central hospitals in Malawi. Hospital-based care was compared to a community-based approach for patients on TB retreatment in which ‘guardians’ (patient-nominated lay people) were trained to deliver injections to patients at home. This study is the qualitative evaluation of the TB-RROC trial. It examines the experiences of people receiving injectables as part of TB treatment delivered in hospital and community-based settings.MethodsA qualitative evaluation of the TB-RROC intervention was conducted using phenomenographic methods. Trial participants were purposively sampled, and in-depth interviews were conducted with patients and guardians in both arms of the trial. Key informant interviews and observations in the wards and community were performed. Thematic content analysis was used to derive analytical themes.ResultsFourteen patients, 12 guardians and 9 key informants were interviewed. Three key themes relating to TB retreatment emerged: medical experiences (including symptoms, treatment, and HIV); the effects of the physical environment (conditions on the ward, disruption to daily routines and livelihoods); and trust (in other people, the community and in the health system). Experiences were affected by the nature of a person’s prior role in their community and resulted in a range of emotional responses. Patients and guardians in the community benefited from better environment, social interactions and financial stability. Concerns were expressed about the potential for patients’ health or relationships to be adversely affected in the community. These potential concerns were rarely realised.ConclusionsGuardian administered intramuscular injections were safe and well received. Community-based care offered many advantages over hospital-based care for patients receiving long-term injectable treatment for TB and their families.