Tuberculosis (TB) remains a significant public health issue globally, with extra pulmonary tuberculosis (epTB) accounting for a considerable number of TB cases. This study aims to improve our understanding of epTB epidemiology by evaluating treatment outcomes and identifying factors associated with positive and negative treatment results in epTB patients. A retrospective study was conducted from January 1, 2016, to December 31, 2019. EpTB and rifampicin-resistant epTB were identified using the GeneXpert MTB/RIF assay. Logistic regression analysis was performed to determine the associated risk factors. Among the 4,526 patients with extra pulmonary tuberculosis, the positivity rate of Mycobacteriuum tuberculosis among the epTB was 16.5%, and the rate of rifampicin-resistant epTB was 4.83%. Most of patients had lymphadenitis TB (n = 348, 38.79%), followed by those with pus (n = 241, 31.95%). Of 746 epTB cases, 679 patients (91.02%) achieved successful treatment outcomes. Of the 36 patients with rifampicin-resistant epTB, 30 (83.3%) exhibited successful treatment outcomes. Tuberculous peritonitis (OR: 1.58), aspirate (OR: 1.59), gastric lavage (OR: 1.45), biopsy (OR: 1.73), Tuberculosis meningitis (TBM) (OR: 1.46), and tissue samples (OR: 3.33) were all significantly associated with unfavourable treatment outcomes. Patients with extrapulmonary tuberculosis (epTB) aged between 35 and 44 had a significantly higher likelihood of experiencing unsuccessful outcomes (OR = 1.79; 95% CI: 0.74–4.31, p = 0.0912). Additionally, individuals with a history of alcohol use showed a higher likelihood of poor outcomes (OR = 1.90; 95% CI: 0.25–14.42). Moreover, tuberculosis patients who used tobacco also had an increased likelihood of unfavourable treatment outcomes (OR = 2.62; 95% CI: 0.35–19.68).The study indicated that the rate of favourable treatment outcomes among epTB patients surpassed the World Health Organization’s target of ≥ 90%. However, a significant number of patients were lost to follow-up during treatment.

E. coli is one of the first commensal bacteria to colonize the chicken gut. It may act as a source for the spread of antibiotic resistance to human via the food chain and contamination of the environment. Isolation and characterization of such E. coli from commercial broilers in retail outlets of Southern India were carried out. Eighty-three E. coli isolates (76.9%) were obtained from cloacal/meat swabs (108 samples). Phenotypically, 78.3% of isolates were ESBL producers, 69.9% were fluoroquinolone-resistant, and 6% were carbapenemase producers. Genotypically, the blaSHV, blaTEM, and blaCTX-M were present in 48.2%, 43.4%, and 10.8% of the isolates, respectively. These isolates also carried fluoroquinolone-resistant genes viz qnrB (31.3%) and qnrS (34.9%) but not carbapenemase genes. Overall, ESBL were identified in 72.3% of isolates and fluoroquinolone-resistance genes in 51.8%. Strikingly, 53% of the isolates were multidrug-resistant, with both ESBL and fluoroquinolone-resistant genes. The study revealed the presence of MDR E. coli strains in broiler meat at retail outlets indicating the potential public health risks.

Enhancing treatment outcomes for drug-resistant tuberculosis is a major global priority for tuberculosis control programs. India has the highest number of Multidrug-resistant Tuberculosis cases worldwide, yet no longitudinal studies have assessed the factors affecting treatment outcomes in public sector conditions. This study aimed to evaluate factors associated with ineffective treatment outcomes in patients with Multidrug-resistant Tuberculosis receiving outpatient care under the National Tuberculosis Elimination Programme in Puducherry, India, from January 2020 to December 2023. We employed multivariate regression methods to calculate odds ratios with 95% confidence intervals to identify factors linked to unsuccessful treatment outcomes. Clinical data from patients with Multidrug-resistant Tuberculosis revealed an overall treatment success rate of 60.42%. The findings showed that patients undergoing retreatment were more likely to experience unsuccessful outcomes. Additionally, co-infection with HIV, as well as the use of alcohol or tobacco, increased the odds of treatment failure. Patients with heteroresistant patterns had 2.72 times higher odds of unsuccessful treatment outcomes compared to those with inferred and true-resistant patterns. Furthermore, patients living in rural areas typically experienced worse treatment outcomes than those in urban areas, with higher rates of loss to follow-up. Patients on longer treatment regimens were also more likely to be lost to follow-up compared to those on shorter regimens. Notably, true resistance due to rpoB gene mutations accounted for 65.9% (29 out of 44) of total deaths, with mutations at codon S450L contributing to 47.7% of these fatalities, a finding that has not been reported elsewhere. The study highlighted a strong association between heteroresistance in the rpoB gene and poor treatment outcomes. These results emphasize the need for detailed molecular-level studies to improve treatment outcomes by ensuring appropriate drug selection for MDR/RR Tuberculosis. Additionally, further research is necessary to determine the impact of heteroresistance on treatment outcomes in individual patients.

Although many studies have examined the connection between mutations in the rpoB gene and drug resistance, the impact of common mutations on treatment outcomes for RR-TB is not yet fully understood. This study explores the relationship between rpoB gene mutations and drug-resistant phenotypes, assesses their role in predicting RR-TB prognosis, and investigates the impact of disputed rpoB mutations in M. tuberculosis on treatment outcomes. 192 rifampicin-resistant isolates were retested for drug susceptibility and gene sequencing. Minimum inhibitory concentrations (MICs) were determined for 98 isolates with disputed rpoB gene mutations. These mutations can cause low-level resistance to rifampicin, leading to inconsistencies in drug susceptibility testing and impacting medication therapy decisions. Of 192 cases, 116 (60.4

GeneXpert MTB/RIF is a rapid molecular diagnostic tool capable of simultaneously detecting Mycobacterium tuberculosis and rifampicin resistance. This study aimed to assess the diagnostic precision of GeneXpert MTB/RIF assay to detect pulmonary and extrapulmonary tuberculosis and evaluate the performance for detecting of rifampicin resistance. Of 37,695 samples, 7156 (18.98%) were tuberculosis-positive, and 509 (7.11%) were rifampicin-resistant. The sensitivity, specificity, positive predictive value, negative predictive value, disease prevalence, and accuracy of the GeneXpert MTB/RIF assay for pulmonary tuberculosis were 99.87% (95%CI: 99.75–99.94), 99.92% (95%CI: 99.88–99.95), 99.71% (95%CI: 99.54–99.82), 99.97% (95%CI: 99.93–99.98), 21.38% (95%CI: 20.92–21.86), and 99.91% (95%CI: 99.87–99.94), respectively. For extrapulmonary tuberculosis, the sensitivity, specificity, PPV, NPV, disease prevalence, and accuracy of GeneXpert MTB/RIF assay accounted for 99.45% (95%CI: 98.73–99.82), 99.84% (95%CI: 99.73–99.92), 98.70% (95%CI: 97.73–99.25), 99.93% (95%CI: 99.84–99.97), 10.64% (95%CI: 9.99–11.31), and 99.80% (95%CI: 99.68–99.88), respectively. Despite its high sensitivity for detecting tuberculosis and rifampicin resistance, GeneXpert MTB/RIF had contradictory results for 20.5% of cases among patients with smear-negative results and 54.9% of cases among patients with a high risk of multidrug-resistant tuberculosis. Of 46% fluoroquinolone-resistant cases, 16.56% (26/157) were multidrug-resistant tuberculosis isolates, and 4.02% (20/498) were isoniazid-resistant, a characteristic distribution leading to about 17.2% of fluoroquinolone-resistance events and relevant marker gyr-A mutations in MDR tuberculosis isolates. Further, our study indicated that increased fluoroquinolone resistance among rifampicin-resistant and isoniazid-resistant tuberculosis endangers the success of newly endorsed MDR-TB regimens.

Background: The production of a variety of chalcones (1-Aryl/Alkyl amino substituted-dene-2(-1,3-diphenylallylidene) hydrazine (ABSa-e) was brought about as a result of the condensation of hydrazide compound and Aryl/Alkyl substituted aldehyde/ ketone in ethanol as a solvent with the help of two drops of conc. hydrochloric acid as a catalyst followed by neutralization. All synthesized derivatives were identified with different spectroscopic techniques and biologically evaluated by microorganisms. Materials and Methods: The in vitro antibacterial and antifungal activity of all synthesised compounds was evaluated. In the microbial studies, the five strains of selected bacteria and two strains of fungi have been used to evaluate the synthesized compounds, DMSO used as the solvent, and amoxicillin and griseofulvin used as control drugs. Results and Conclusion: Derivatives exhibited the highest potency (17mm, 18mm, 16mm, 18mm, 15mm) (MIC) with the electron donating groups (CH3) in position 4 of the phenyl ring (ABSc). On the other hand, the withdrawing group (NO2, Cl) of compounds ABSb & ABSe showed the most negligible potency against selected microorganisms. The unsubstituted phenyl ring oxygen-containing furan compound ABSd proved as the second-highest potency (16mm, 17mm, 15mm, 17mm, 14mm) of this series. All of the results pointed to compound ABSc as a potential antibacterial lead molecule, and efforts are currently being made to increase the potency of amino chalcone derivatives.

Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDRsl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34–20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25–3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher.

IntroductionMycobacterium tuberculosis has been extensively studied for mutations leading to drug resistance. Pyrazinamide is a drug acting on the semi-dormant bacteria that is responsible for relapse of tuberculosis. This drug helped reduce the treatment duration of tuberculosis from nine to six months. However, this drug is not being screened for resistance along with Rifampicin and Isoniazid.Aims and objectivesThis study aimed to estimate the proportion of pncA gene mutation among tuberculosis patients and its association between treatment outcomes, clinical characteristics, and phenotypic drug resistance.Methodology: A total of 154 samples included 73 drug-resistant and 81 drug-susceptible isolates. The isolates were subjected to DNA extraction and amplification using conventional PCR. The PCR product was sequenced by the Sanger sequencing method, and phenotypic drug susceptibility testing was done using the broth dilution method. The association of this gene with the treatment outcome was done by following up with the patients till the end of the regimen.ResultsNone of the drug susceptible tuberculosis patients showed significant non-synonymous mutations. Among the drug-resistant TB patients, seven unique significant mutations out of 73 isolates (9.6%) were distributed among Isoniazid-resistant tuberculosis and Multi-Drug Resistant Tuberculosis isolates. No association was found between the mutations and the clinical characteristics of the subjects harboring these isolates.ConclusionThis study estimated seven unique mutations in drug-resistant tuberculosis and none in drug-sensitive tuberculosis. Isolates harboring was not significantly associated with the participant's treatment outcome and other clinical characteristics. The pyrazinamide resistance testing by the phenotypic and genotypic methods was found to be in concordance.

PURPOSE:We aimed this study to standardize real time - polymerase chain reaction (RT-PCR) for the detection of Mycobacterium tuberculosis (Mtb) in cerebrospinal fluid (CSF) samples and compare its diagnostic performance with GeneXpert (Xpert), Mycobacteria Growth Indicator Tube (MGIT) and Multiplex PCR (MPCR) for tuberculous meningitis (TBM).METHODOLOGY:A total of 217 CSF samples were obtained from patients with suspected TBM during the study period between January 2019 and December 2021. The optimal cycle threshold (CT) of RT-PCR was determined by comparing different gene targets of Mtb (IS6110, 16SrRNA, HSP65 and Ag85B). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was determined for RT-PCR, Xpert, MGIT960 and MPCR. Diagnostic accuracy of these assays was compared by using clinical diagnosis as reference standard.RESULTS:IS6110RT-PCR was found to be highly sensitive as compared to other gene targets. Sensitivities of IS6110RT-PCR, MPCR, Xpert and MGIT against a reference standard of definite, probable and possible TBM were 36.7%, 21.1%, 16.7% and 6.7%, respectively; specificities were 97.6%, 100%, 100% and 100%, respectively. Xpert, RT-PCR, MPCR and MGIT960 detected 6.91% (n = 15), 5.99% (n = 13), 5.99% (n = 13) and 2.76% (n = 6) of definite TBM, respectively. RT-PCR detected 6.45% (n = 14) and 2.76% (n = 6) of possible TBM and probable TBM, respectively and MPCR detected 1.38% (n = 3) of possible and probable TBM each.CONCLUSION:IS6110RT-PCR is highly sensitive for primary screening of suspected TB cases, which may help clinicians to start appropriate patient's treatment with clinical suspicion of TBM.

India contributes to approximately one-third of total global tuberculosis (TB) and one-fourth of all Multi-Drug Resistant TB (MDR-TB) burden respectively. The First National drug resistance survey (2014-16) showed MDRTB rates of 6.19% overall and 2.14% in newly diagnosed TB cases. With the above problem of primary drug resistance among newly diagnosed tuberculosis cases, the present study was planned to find the prevalence of Isoniazid (INH) and Rifampicin resistance in the treatment naïve new tuberculosis cases.: Study design: Prospective, cross-sectional.: Treatment naive newly diagnosed pulmonary tuberculosis cases.: 125.: After informed written consent, Sputum samples were collected and subjected to culture in MGIT 960 and positive cultures were recorded and subjected to drug sensitivity testing for INH (0.1 μg/ml) and Rifampicin (1 μg/ml) and a parallel non-drug MGIT was run as a control.: Most cases were males and belonged to the 20-59 years age group. Isoniazid (INH) resistance was found in 7 out of 125 samples, none had resistance to rifampicin. None of the categorical variables or grading of smear were having any statistically significant correlation with INH resistance.: INH resistance was found to be low (5.6%) with negligible MDR in the current study. Regular and large studies are needed to quantify and tackle the problem of primary MDR TB.

Microbial Fuel Cells (MFCs) are a rapidly expanding area of sustainable technology that treats wastewater and generates energy from biodegradable wastes at the same time. However, the power generation from MFC is strongly restricted by the biofilm (microorganism) electron transfer rate which improves electrical power density. The current study provides insight into the effectiveness in electricity production, and wastewater treatment using MFC technique by identifying microbial electricigens on various electrodes using raw fish market wastewater effluent as a substrate. Galvanised iron, aluminium, brass, stainless steel (metal-based electrodes), and graphite rod (carbon-based electrode) were used for the study. MALDI-TOF MS tests were performed to identify the predominant bacterial species from each electrode containing reactors. Raoultella ornithinolytica, Comamonas testosteroni, and Klebsiella pneumonia were among the microbes that were identified and isolated from the anodic biofilm of different MFC reactors. In the current study, four out of the five reactors contained R. ornithinolytica, which was found to be effective at generating electricity. The fuel cell produced maximum current density of 325.13 mA/m2, and power density of 87.78 mW/m2. The COD removal efficiency was found to be 86 %. This study demonstrates the significance of bacterial community characterization and identification in MFC-assisted current generation in fish market wastewater.

Background:Tuberculous meningitis (TBM) is caused by the dissemination of Mycobacterium tuberculosis (MTB) from the primary site of infection to the central nervous system. However, the bacterial factors associated with the pathogenesis of TBM remain unclear. This study employed transcriptomic and proteomic methods to comprehensively analyze the changes in genes and proteins and their associated pathways in MTB strains isolated from cerebrospinal fluid (CSF) of TBM and sputum of pulmonary TB (PTB) cases. Methodology:Five MTB strains were subjected to OMICs (transcriptomic and proteomic) analysis. Among five MTB strains, two were isolated from CSF and sputum samples of the same patient with PTB and TBM infections, one from the sputum of a different PTB patient, and a strain obtained from the CSF of another TBM patient. H37Rv was used as a reference strain. The reliability of transcriptomic results was validated by real time polymerase chain reaction with selected genes from 100 MTB isolates (CSF, 50 and sputum, 50). Results:The transcriptomic study revealed that overlapping differentially expressed genes of MTB strains isolated from TBM patients showed featured enrichment in benzoate degradation, lysine degradation, tryptophan metabolism, fatty acid degradation, ATP binding cassette transporters, microbial metabolism in diverse environments, biosynthesis of antibiotics, and metabolic pathways. Eleven genes were upregulated, and four were downregulated in MTB strains isolated from TBM compared to PTB. From proteomic analysis, we identified three candidate proteins belonging to plasminogen binding proteins (PBP) (enolase, dnaK, and isocitrate lyase 1) that were significantly upregulated in MTB strains isolated from TBM. Conclusion:Overall, the transcriptomic and proteomic analyses provided an important base for understanding the unique feature of TBM pathogenesis. To the best of our knowledge, this is the first report highlighting the importance of PBPs on TBM pathogenesis.