Anti-tuberculosis Research Articles

Pattern of Adverse Drug Reactions and Performed Monitoring Laboratory-Tests in Patients Receiving Anti Tuberculosis Treatment in an Endemic Region, Zabol

Background: Efficient anti TB treatment considered crucial globally. Anti TB drugs can cause various adverse drug reactions (ADRs). Clinical and laboratory monitoring will decrease rate of these ADRs, improve patient safety as well as drug adherence and treatment outcome. Methods: In this cross-sectional study total of 136 newly diagnosed TB patients were included. All patients received standard anti-TB 4 drug regimen. Predesigned data collection forms were used to gather patient’s lab data as well as clinical symptoms they experienced during treatment course. Monthly follow up visits or phone calls were also performed by investigators and all health issues were recorded. Results: The majority of our patients aged over 70-year-old. About 54% of them were female. We recorded at least one ADR in 80.8% of patients, and hepatic-gastrointestinal (GI) ADRs ranked first (64.7%). Although ADRs were more common in women and patients over 70-year-old, but there was no statistically significant relationship between sex or age and rate of ADRs (P> 0.05). We also observed that recommended baseline laboratory tests for monitoring anti TB treatment was not performed in any of our patients, except complete blood count (CBC) that was performed in 11 cases. This led to diagnoses of anemia and thrombocytopenia in one case. Conclusion: The majority of our patients experienced ADR. Recommended drug monitoring tests that could guarantee safe and effective treatment were not performed routinely in our TB management centres. These facts highlighted the importance of improving surveillance system for TB management based on national standards.

Exploring Benzo[h]chromene Derivatives as Agents against Protozoal and Mycobacterial Infections

Background/Objectives: In this study, the efficacy of benzo[h]chromene derivatives as antiprotozoal and antimycobacterial agents was explored. Methods: A total of twenty compounds, including benzo[h]chromene alkyl diesters and benzo[h]chromene-triazole derivatives, were synthesized and tested against Trypanosoma cruzi, Leishmania braziliensis, L. infantum, and strains of Mycobacterium abscessus and Mycobacterium intracellulare LIID-01. Notably, compounds 1a, 1b, 2a, and 3f exhibited superior activity against Trypanosoma cruzi, with IC50 values of 19.2, 37.3, 68.7, and 24.7 µM, respectively, outperforming the reference drug benznidazole (IC50: 54.7 µM). Results: Compounds 1b and 3f showed excellent selectivity indices against Leishmania braziliensis, with SI values of 19 and 18, respectively, suggesting they could be potential alternatives to the commonly used, but more selective, miltefosine (IC50: 64.0 µM, SI: 43.0). Additionally, compounds 1a, 1b, and 3f were most effective against Leishmania infantum, with IC50 values of 24.9, 30.5, and 46.6 µM, respectively. Compounds 3f and 3h were particularly potent against various Mycobacterium abscessus strains, highlighting their significance given the inherent resistance of these bacteria to standard antimicrobials. Conclusions: The sensitivity of Mycobacterium intracellulare LIID-01 to these compounds also underscored their potential in managing infections by the Mycobacterium avium–intracellulare complex.

Allosteric coupling of substrate binding and proton translocation in MmpL3 transporter from Mycobacterium tuberculosis.

Infections caused by Mycobacterium spp. are very challenging to treat, and multidrug-resistant strains rapidly spread in human populations. Major contributing factors include the unique physiological features of these bacteria, drug efflux, and the low permeability barrier of their outer membrane. Here, we focus on MmpL3 from Mycobacterium tuberculosis, an essential inner membrane transporter of the resistance-nodulation-division superfamily required for the translocation of mycolic acids in the form of trehalose monomycolates (TMM) from the cytoplasm or plasma membrane to the periplasm or outer membrane. The MmpL3-dependent transport of TMM is essential for the growth of M. tuberculosis in vitro, inside macrophages, and in M. tuberculosis-infected mice. MmpL3 is also a validated target for several recently identified anti-mycobacterial agents. In this study, we reconstituted the lipid transport activity of the purified MmpL3 using a two-lipid vesicle system and established the ability of MmpL3 to actively extract phospholipids from the outer leaflet of a lipid bilayer. In contrast, we found that MmpL3 lacks the ability to translocate the same phospholipid substrate across the plasma membrane indicating that it is not an energy-dependent flippase. The lipid extraction activity was modulated by substitutions in critical charged and polar residues of the periplasmic substrate-binding pocket of MmpL3, coupled to the proton transfer activity of MmpL3 and inhibited by a small molecule inhibitor SQ109. Based on the results, we propose a mechanism of allosteric coupling wherein substrate translocation by MmpL3 is coupled to the energy provided by the downhill transfer of protons. The reconstituted activities will facilitate understanding the mechanism of MmpL3-dependent transport of lipids and the discovery of new therapeutic options for Mycobacterium spp. infections.IMPORTANCEMmpL3 from Mycobacterium tuberculosis is an essential transporter involved in the assembly of the mycobacterial outer membrane. It is also an important target in undergoing efforts to discover new anti-tuberculosis drugs effective against multidrug-resistant strains spreading in human populations. The recent breakthrough structural studies uncovered features of MmpL3 that suggested a possible lipid transport mechanism. In this study, we reconstituted and characterized the lipid transport activity of MmpL3 and demonstrated that this activity is blocked by MmpL3 inhibitors and substrate mimics. We further uncovered the mechanism of how the binding of a substrate in the periplasmic domain is communicated to the transmembrane proton relay of MmpL3. The uncovered mechanism and the developed assays provide new opportunities for mechanistic analyses of MmpL3 function and its inhibition.

Exploration of vanoxerine analogues as antibacterial agents.

Mycobacterium tuberculosis is a bacterial pathogen, responsible for approximately 1.3 million deaths in 2022 through tuberculosis infections. The complex treatment regimen required to treat tuberculosis and growing rates of drug resistance, necessitates the development of new anti-mycobacterial agents. One approach is to repurpose drugs from other clinical applications. Vanoxerine (GBR 12909) was previously shown to have anti-mycobacterial activity, through dissipating the membrane electric potential and hence, cellular energetics. Several vanoxerine analogues were synthesised in this study, which exhibited a range of activities against mycobacteria and enterococcus. All active analogues had similar impacts on the membrane electric potential and inhibition of ethidium bromide efflux. The most active compound displayed reduced inhibitory activity against the known human target of vanoxerine, the dopamine transporter. This work has identified a promising analogue, which could provide a starting point for further medicinal chemistry and drug development efforts to target mycobacteria.

EVALUASI PENGGUNAAN OBAT ANTITUBERKULOSIS PARU DIPUSKESMAS: NARRATIVE LITERATURE REVIEW

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. While it primarily affects the lungs, it can also impact other organs. In Indonesia, pulmonary TB remains a significant health issue. This study aims to evaluate the use of anti-tuberculosis medications at various community health centers (puskesmas) in Indonesia through a literature review. The research method employed involves a literature review with searches conducted on Google Scholar and PubMed databases. Out of 360 articles found on Google Scholar and 13,026 articles on PubMed, 8 relevant articles were identified for this study. The results indicate that the most commonly used treatment regimen is Category 1, which includes a 2-month intensive phase with a combination of Isoniazid 75 mg, Rifampicin 150 mg, Pyrazinamide 400 mg, and Ethambutol 275 mg, followed by a 4-month continuation phase with Rifampicin 150 mg and Isoniazid 150 mg. This medication regimen aligns with the Tuberculosis Control Guidelines issued by the Indonesian Ministry of Health in 2016. The evaluation shows that Indonesian puskesmas generally adhere to the established treatment guidelines but still require further monitoring to ensure adherence and effectiveness of the treatment.

Cervical Lymphadenitis Tuberculosis Coexistent with Metastatic Papillary Thyroid Carcinoma.

Malignant lesions and tuberculosis coexisting at the same anatomical site in a patient are extremely uncommon. We present a case of a 53-year-old female with cervical lymphadenitis tuberculosis combined with metastatic papillary thyroid carcinoma. Thyroidectomy was performed on the patient with central and lateral neck dissection. The patient received anti-tuberculosis medication and radioactive iodine ablation. No recurrence was observed during a 2-year follow-up period.

Natural and Bioinspired Lipidic Alkynylcarbinols as Leishmanicidal, Antiplasmodial, Trypanocidal, Fungicidal, Antibacterial, and Antimycobacterial Agents.

The present review article recapitulates for the first time the antipathogenic biological data of a series of lipidic natural products and synthetic analogues thereof characterized by the presence in their structure of an alkynylcarbinol unit. The cytotoxic properties of such natural and bioinspired compounds have been covered by several literature overviews, but to date, no review article detailing their activity against pathogens has been proposed. This article thus aims at providing a comprehensive overview of the field including early studies from the 1970s and 1980s with a specific focus on results published from the late 1990s until nowadays. Publications presenting the data of almost 50 different natural products are reported. Detailed activities encompass the fields of leishmanicidal, antiplasmodial, trypanocidal, fungicidal, and mainly antibacterial and antimycobacterial compounds. The few published studies aimed at exploring the structure-activity relationship in these series are also described. Around 15 different synthetic analogues of natural products, selected among the most active reported, are also presented. The rare data available regarding the antipathogenic mode of action of these products are recalled, and finally, a comparative analysis of the available biological data is proposed with the aim of identifying the key structural determinants for the bioactivity against pathogens of these unusual compounds.

A network pharmacology-based approach to understand the mechanism of action of anti-mycobacterial activity of Acacia nilotica: a modelling and experimental study.

The rapid rise in drug-resistant tuberculosis poses a serious threat to public health and demands the discovery of new anti-mycobacterial agents. Medicinal plants are a proven potential source of bioactive compounds; however, identifying those responsible for the putative anti-mycobacterial action still remains a challenging task. In this study, we undertook a systematic network pharmacology approach to identify and evaluate anti-mycobacterial compounds from a traditional plant, Acacia nilotica, as a model system. The protein-protein interaction network revealed 17 key pathways in M. tuberculosis encompassing 40 unique druggable targets that are necessary for its growth and survival. The phytochemicals of A. nilotica were preferentially found to interfere with the cell division and cell wall biogenesis proteins, especially FtsZ and Mur. Notably, the compounds epigallocatechin, ellagic acid, chlorogenic acid, and D-pinitol were found to exhibit a potential polypharmacological effect against multiple proteins. Further, in vitro studies confirmed that the selected candidates, chlorogenic acid, and ellagic acid exhibited potent anti-mycobacterial activity (against M. smegmatis) with specific inhibition of purified M.tb FtsZ enzyme. Taken together, the present study demonstrates that network pharmacology combined with molecular docking can be utilized as an efficient approach to identify potential bioactive phytochemicals from natural products along with their mechanism of action. Hence, the compounds identified in this study can be potential lead candidates for developing novel anti-mycobacterial drugs, while the key proteins identified here can be potential drug targets.

The Relationship Between Compliance in Taking Anti Tuberculosis Drugs and the Results of Acid-Fast Bacteria (AFB) Examination as an Indicator of Recovery of TB Patients in Tanjung Pinang City in 2022-2023

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis with a treatment period of 6 to 8 months. Mycobacterium tuberculosis can become germ resistant or multidrug resistance (MDR) if you do not comply in taking anti-tuberculosis drugs (ATD), making this disease very difficult to cure. This research uses secondary data from the Tanjung Pinang City Population Control and Family Planning Health Service for 2022-2023. The aim is to determine the relationship between compliance in taking Anti-Tuberculosis Drugs (ATD) and the results of acid-fast bacteria (AFB) examinations of TB patients in Tanjung Pinang City. The research methodology was observational analytic using a cross-sectional design, with a total sampling technique from pulmonary TB patients with positive AFB, negative AFB with positive thorax and extrapulmonary, 252 TB patients. Data analysis used the Fisher Exact test with a confidence level of 95%. The results of data analysis showed that 91.3% of patients complied in taking drugs, and 87.3% recovered with negative AFB results. Fisher Exact analysis showed a significant difference in proportion between compliance in taking anti-tuberculosis drugs and the results of AFB examination of pulmonary TB patients with a p-value of 0.000 (p < ∝0.05). The conclusion from this study is that there is a relationship between compliance in taking anti-tuberculosis drugs and the results of AFB examinations of pulmonary TB patients in Tanjung Pinang City in 2022-2023. Keywords: Pulmonary TB, ATD, (AFB), Ziehl Neelsen

Repurposing antiparasitic N,N'-aliphatic diamine derivatives as promising antimycobacterial agents.

In previous studies, we demonstrated the potent activity of a library of 25 N,N'-disubstituted diamines (NNDDA) toward Trypanosomatid and Apicomplexa parasites. Considering the structure similarity between this collection and SQ109, an antituberculosis compound, and its compelling antiparasitic properties, we aimed to repurpose this library for tuberculosis treatment. We assayed this collection against Mycobacterium tuberculosis H37Rv and M. avium, obtaining several compounds with MIC values below 10 µM. The most active analogs were also evaluated against M. smegmatis, a non-pathogenic species, and the non-tuberculosis mycobacteria M. abscessus, M. kansasii, and M. fortuitum. 3c stands out as the lead mycobacterial compound of the collection, with potent activity against M. tuberculosis (minimal inhibitory concentration [MIC] = 3.4 µM) and moderate activity against M. smegmatis, M. kansasii, and M. fortuitum (all with MIC values of 26.8 µM). To unravel the mechanism of action, we employed the web-based platform Polypharmacology Browser 2 (PPB2), obtaining carbonic anhydrases as potential drug targets. Nevertheless, none of the compounds displayed experimental inhibition. In summary, our study confirms the validity of the repurposing approach and underscores the antimycobacterial potential of NNDDA compounds, especially the analog 3c, setting a stepping stone for further studies.

Discovery of potent anti–tuberculosis agents targeting aminoacyl–tRNA synthetases

Discovery of potent anti–tuberculosis agents targeting aminoacyl–tRNA synthetases

Sequential and parallel testing for microbiological confirmation of tuberculosis disease in children in five low-income and middle-income countries: a secondary analysis of the RaPaed-TB study

Despite causing high mortality worldwide, paediatric tuberculosis is often undiagnosed. We aimed to investigate optimal testing strategies for microbiological confirmation of tuberculosis in children younger than 15 years, including the yield in high-risk subgroups (eg, children younger than 5 years, with HIV, or with severe acute malnutrition [SAM]). For this secondary analysis, we used data from RaPaed-TB, a multicentre diagnostic accuracy study evaluating novel diagnostic assays and testing approaches for tuberculosis in children recruited from five health-care centres in Malawi, Mozambique, South Africa, Tanzania, and India conducted between Jan 21, 2019, and June 30, 2021. Children were included if they were younger than 15 years and had signs or symptoms of pulmonary or extrapulmonary tuberculosis; they were excluded if they weighed less than 2 kg, had received three or more doses of anti-tuberculosis medication at time of enrolment, were in a condition deemed critical by the local investigator, or if they did not have at least one valid microbiological result. We collected tuberculosis-reference specimens via spontaneous sputum, induced sputum, gastric aspirate, and nasopharyngeal aspirates. Microbiological tests were Xpert MTB/RIF Ultra (hereafter referred to as Ultra), liquid culture, and Löwenstein-Jensen solid culture, which were followed by confirmatory testing for positive cultures. The main outcome of this secondary analysis was categorising children as having confirmed tuberculosis if culture or Ultra positive on any sample, unconfirmed tuberculosis if clinically diagnosed, and unlikely tuberculosis if neither of these applied. Of 5313 children screened, 975 were enrolled, of whom 965 (99%) had at least one valid microbiological result. 444 (46%) of 965 had unlikely tuberculosis, 282 (29%) had unconfirmed tuberculosis, and 239 (25%) had confirmed tuberculosis. Median age was 5·0 years (IQR 1·8-9·0); 467 (48%) of 965 children were female and 498 (52%) were male. 155 (16%) of 965 children had HIV and 110 (11%) children had SAM. 196 (82%) of 239 children with microbiological detection tested positive on Ultra. 110 (46%) of 239 were confirmed by both Ultra and culture, 86 (36%) by Ultra alone, and 43 (18%) by culture alone. 'Trace' was the most common semiquantitative result (93 [40%] of 234). 481 (50%) of 965 children had only one specimen type collected, 99 (21%) of whom had M tuberculosis detected. 484 (50%) of 965 children had multiple specimens collected, 141 (29%) of whom were positive on at least one specimen type. Of the 102 children younger than 5 years with M tuberculosis detected, 80 (78%) tested positive on sputum. 64 (80%) of 80 children who tested positive on sputum were positive on sputum alone; 61 (95%) of 64 were positive on induced sputum, two (3%) of 64 were positive on spontaneous sputum, and one (2%) was positive on both. High rates of microbiological confirmation of tuberculosis in children can be achieved via parallel sampling and concurrent testing procedures. Sample types and choice of test to be used sequentially should be considered when applying to groups such as children younger than 5 years, living with HIV, or with SAM. European and Developing Countries Clinical Trials Partnership programme, supported by the EU, the UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung, the German Center for Infection Research, and Beckman Coulter.

Symptomatic bradycardia in tuberculosis-related giant bullae (vanishing lung syndrome): A case report

Rationale: Vanishing lung syndrome is rare and can be associated with a history of smoking and marijuana use. The occurrence of giant bullae can also be linked to infections, particularly tuberculosis in tropical countries. Patient concerns: A 26-year-old male complained of weakness, severe vomiting, and reduced breathlessness when lying on the left side. He had a history of pulmonary tuberculosis two years ago. Diagnosis: Symptomatic bradycardia in tuberculosis-related giant bullae. Interventions: The patient was recommended to undergo an elective bullectomy, but he decided not to proceed with the procedure. Atropine sulfate was administered to alleviate symptoms of bradycardia, while a standardized anti-tuberculosis regimen were started for the next six months. Outcomes: Following 7 days of intensive care treatment involving antituberculosis medications and atropine sulfate, the patient achieved hemodynamic stability, opting against bullectomy despite residual symptoms of dyspnea. Subsequent six months of antituberculosis therapy notably alleviated symptoms without requiring bullectomy. Lessons: Increasing intrathoracic pressure can also be caused mechanically by giant bullae. Cardiac symptoms in vanishing lung syndrome are reversible and can be alleviated once the underlying cause is addressed. In this case, symptomatic bradycardia was reduced only with tuberculosis treatment without bullectomy intervention.

The Impact Of Clients' Knowledge On Compliance With Anti-Tuberculosis Medication At Home

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, namely acid-fast bacteria. Successful treatment of patients with tuberculosis (TB) is a problem in today's society. One of the reasons for the increase in pulmonary TB cases is the low level of education of sufferers. One of the causes of failure of tuberculosis treatment therapy is the side effects of anti-tuberculosis drugs (OAT) which can affect the adherence to medication in tuberculosis patients. The success of TB treatment is compliance in taking anti-tuberculosis medication at the prescribed dose. The aim of this research was to determine the relationship between clients' knowledge of pulmonary tuberculosis and compliance with taking anti-pulmonary tuberculosis medication at Harapan Pematang Siantar Hospital. This research was conducted at Harapan Pematangsiantar Hospital in May 2023. This type of research is descriptive quantitative correlational with a cross-sectional approach. Data collection was carried out using a questionnaire with the Gutman scale. The population of this study was all outpatient clinic patients at Harapan Pematang Siantar Hospital in October-December 2022. The sampling technique was accidental sampling, namely 58 respondents who came in May 2023. Statistical test results used the chi square test with a confidence level of 95% (α = 0.05) shows the p value = 0.001, meaning that there is a relationship between the level of knowledge of tuberculosis clients and compliance with taking anti-tuberculosis medication at Harapan Pematang Siantar Hospital in 2023

Synthesis and antitubercular activities of acetamide-substituted benzazole derivatives

Multidrug-resistant Mycobacterium tuberculosis strains' increasing emergence and rapid spread necessitate the urgent development of innovative antimycobacterial agents. In pursuit of novel agents, a series of N-(benzazole-2-ylmethyl)-2-substituted phenylacetamide or N-(benzazole-2-ylmethyl)-2-(thiophen-2-yl)acetamide compounds (6-11) were synthesized. Their efficacy against multidrug-resistant Mycobacterium tuberculosis was assessed. Compounds exhibited potent antimycobacterial activity with minimum inhibitory concentrations (MIC) ranging from 1.05 to 4.10 µM and demonstrated low cytotoxicity towards fibroblast cell line (L929). ADMET predictions suggested that these synthesized compounds possess drug-like properties. Our findings offer a promising starting point for designing more selective and potent antimycobacterial agents.

Estimating optimal therapeutic drug levels of anti-tuberculosis medications based on treatment safety and effectiveness.

Therapeutic drug ranges (TDR) for standard anti-tuberculosis (TB) treatment have been determined based on expected drug levels at least 2 hours after taking the dose. In this study we constructed TDR for TB drug levels based on minimizing drug toxicity and maximizing treatment effectiveness. Participants were followed prospectively in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil observational cohort study. We focused on participants with culture-confirmed drug-susceptible pulmonary TB who underwent standard TB therapy. TDR were estimated for each TB drug separately: isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA). TDR were defined as drug concentrations that were both safe and effective: safety was defined as the probability of having an ADR of at most 5%, while effectiveness was defined as a probability of at least 95% of not having either TB treatment failure or recurrence. There were 765 plasma samples from 448 patients; 110 (24.6%) were people with HIV, 9 (2.0%) had a grade 3 or higher ADR, and 15 (3.3%) had treatment failure/recurrence. Higher drug concentrations of INH, RIF and EMB were associated with increased odds of having ADR. High concentrations of INH suggested protection against treatment failure/recurrence. Estimated therapeutic drug range for INH (2.3-8.2 µg/ml) and for RIF (0.5-7.5 µg/ml) differed from the currently recommended drug ranges (3-5 µg/ml and 8-24 µg/ml, respectively). Estimates for PZA and EMB were similar to the currently recommended values. Our estimated upper end TDR were higher for INH and lower for RIF compared to currently recommended ranges.

Treatment for multidrug-resistant tuberculosis: A comparative analysis of programmatic outcome indicators between Buenaventura and other municipalities of Valle del Cauca, Colombia

Introduction. Proper management of multidrug-resistant tuberculosis is a prioritized strategy for tuberculosis control worldwide. Objective. To evaluate differences concerning demographic and clinical characteristics and programmatic indicators of Buenaventura patient cohort with confirmed diagnosis of multidrug-resistant tuberculosis, compared to those of the other municipalities from Valle del Cauca, Colombia, 2013-2016. Materials and methods. We conducted an analytical cohort study to compare records of patients older than 15 years with multidrug-resistant tuberculosis included in the Programa de Tuberculosis de Buenaventura (with para-aminosalicylic acid) versus the other municipalities of Valle del Cauca (without para-aminosalicylic). Results. Ninety-nine cases were recorded with a median age of 40 years (IQR = 26 - 53); in Buenaventura, 56% of the patients were women, while in the other municipalities, men predominated with 67%; 95% had health insurance. The most common comorbidity was diabetes (14%). Adverse reactions to antituberculosis medications in Buenaventura were 1.3 times more frequent than in the other municipalities (OR = 2.3; 95% CI = 0.993 - 5.568; p = 0.04). In Buenaventura, the mortality rate was 5% compared to the 15% reported in the other municipalities. Treatment failures were not reported in Buenaventura, but 35% did not continue with the follow-up. Treatment success was higher in Buenaventura (56 %). Conclusion. A strengthened program in Buenaventura presented better programmatic results than those from the other municipalities of Valle del Cauca. Access to molecular tests, availability of shortened treatments, and continuous monitoring to identify adverse reactions to antituberculosis medications are routes for all other control programs.

Nano-Medicine for Treatment of Tuberculosis, Promising Approaches Against Antimicrobial Resistance.

Even though the number of effective anti-tuberculosis or anti-mycobacterial agents is increasing, a large number of patients experience severe side effects as a result of these drugs. This hurts the patients' well-being and quality of life. Tumor cells that survive treatment modalities can become chemotherapy resistant at the molecular level. Furthermore, negative effects on normal cells occur concurrently. Strategies that minimize the negative effects on normal cells while efficiently targeting infected cells are required. Nanotherapies, according to recent research, may be one option in this direction. The present study differs from previously published review studies as it concentrates on examining the most recently developed nanoparticles for anti-mycobacterial purposes. Such novel approaches have the potential to reduce harmful side effects and improve patients' health prognoses.Current paper provides a comprehensive analysis of recent advances in nanotherapy systems for the pulmonary delivery of anti-tuberculous drugs. In addition, to low-priced and convenient alternatives for pulmonary delivery, different types of NPs for oral and topical application were also deliberated and summarized in this review.

Discovery and characterization of a novel LysinB from F2 sub-cluster mycobacteriophage RitSun

The escalating antibiotic resistance in mycobacterial species poses a significant threat globally, necessitating an urgent need to find alternative solutions. Bacteriophage-derived endolysins, which facilitate phage progeny release by attacking bacterial cell walls, present promising antibacterial candidates due to their rapid lytic action, high specificity and low risk of resistance development. In mycobacteria, owing to the complex, hydrophobic cell wall, mycobacteriophages usually synthesize two endolysins: LysinA, which hydrolyzes peptidoglycan; LysinB, which delinks mycolic acid-containing outer membrane and arabinogalactan, releasing free mycolic acid. In this study, we conducted domain analysis and functional characterization of a novel LysinB from RitSun, an F2 sub-cluster mycobacteriophage from our phage collection. Several key properties of RitSun LysinB make it an important antimycobacterial agent: its ability to lyse Mycobacterium smegmatis from without, a higher than previously reported specific activity of 1.36 U/mg and its inhibitory effect on biofilm formation. Given the impermeable nature of the mycobacterial cell envelope, dissecting RitSun LysinB at the molecular level to identify its cell wall-destabilizing sequence could be utilized to engineer other native lysins as fusion proteins, broadening their activity spectrum.

Hepatotoxicity during anti tuberculosis chemotherapy

Introduction: Despite their efficacy in tuberculosis treatment, side-effects of anti-tuberculosis drugs can be serious or fatal. The aim of our study is to determine the prevalence of hepatic toxicities associated with anti-tuberculosis drugs, their evolutionary aspects, and their management. Patients and methods: A retrospective descriptive study including 82 patients having received antituberculosis treatment and who pre-sented a hepatic cytolysis, collected at the Tuberculosis and Respiratory Diseases Control Department of Batna- Algeria between 2016 -2023. The aim of our study is to determine the prevalence of hepatic toxicities of anti-tuberculosis drugs, their evolutionary aspects, as well as the modalities of their management. Results: 82 out of 119 (69.23%) patients who experienced other adverse events were recruited between 2016 and 2023, aged between 15 and 86 years, with an average age of 43 years and a female predominance of 63.41%. Cholestasis syndrome was noted in 21 patients and frank jaundice in 4. Cytolysis was discovered incidentally in 68% of patients; it was mild in 56 (68.29%), moderate in 16 (19.51%) and severe in 10 (12.19%). Transaminase disturbance appeared within 3 months in 76.82% of cases, whereas a delay of 30 days was noted for normalisation of the liver function test after cessation of anti-tuberculosis treatment in 62 (76%) patients. Definitive discontin-uation of isoniazid (INH) was adopted in 17 (20%) patients, while a reduction in the doses of rifampicin and isoniazid was decided in 65 (80%) patients. Conclusion: Drug-induced hepatitis is one of the major side-effects of anti-tuberculosis drugs and can be lethal, hence the need for rapid and appropriate management. Healthcare professionals need to be informed about the types of suspected adverse drug reactions, they should report in subjects at risk.