Analysis of The Correlation Between inhA Gene Mutation and Resistance to Protionamide in Drug-Resistant Mycobacterium Tuberculosis

Objective: To investigate the characteristics of katG and inhA gene mutations in multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant tuberculosis (preXDR-TB), and their correlation with resistance to protionamide (Pto). Methods: A total of 229 patients with MDR-TB and pre-XDR-TB diagnosed in the Eighth Affiliated Hospital of Xinjiang Medical University from January 2020 to February 2024 were selected to analyze the characteristics of katG and inhA mutations in MTB clinical isolates and their correlation with Pto resistance. Results: The mutation rate of katG (with or without inhA mutation) was 85.2%. The mutation rates in MDR-TB and pre-XDR-TB were 87.4% (125/143) and 81.4% (70/86), respectively. The mutation rate of inhA (including katG mutation) was 14.8% (34/229), which was 12.6% (18/143) and 18.6% (16/86) in MDR-TB and pre-XDR-MTB, respectively. There was no difference in mutation (P > 0.05). Conclusion: The total resistance rate to Pto in 229 strains was 8.7% (20/229), which was 8.4% (12/143) and 9.3% (8/86) in MDR-TB and pre-XDR-TB, respectively. Among the inhA mutant strains, 13 were resistant to the Pto phenotype, and the resistance rate was 65% (13/20). In MDR-TB and pre-XDR-TB strains resistant to Pto, inhA gene mutations occurred in 66.7% (6/9) and 63.6% (7/11), respectively. The resistance rates of MDR-MTB and pre-XDR-TB strains without inhA gene mutation to Pto were 2.4% (3/125) and 5.7% (4/70), respectively.

Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the catastrophic costs DRTB patients incur.

Research progress on the drug action and resistance mechanism in Mycobacterium tuberculosis

Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.

The Role of Pyridoxine in the Prevention and Treatment of Neuropathy and Neurotoxicity Associated with Rifampicin-Resistant Tuberculosis Treatment Regimens: A Topic Review

Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.

First Nationwide Survey on the Resistance to First Line Anti-Tuberculosis Drugs in Ghana

Background/objective: A nationwide survey on the resistance to first line anti-tuberculosis (anti-TB) drugs was conducted in Ghana from 2007-2008 by Noguchi Memorial Institute for Medical Research in collaboration with the National Tuberculosis Control Programme. We aimed to characterize mycobacterial species causing pulmonary tuberculosis (PTB) and determine the resistance pattern to first line anti-TB drugs among newly diagnosed and previously treated PTB patients in Ghana. Methods: Two sputum samples from consented new smear positive PTB patients who had never been treated for TB or had been on anti-TB treatment for less than a month and patients who had been treated for TB previously for more than a month in selected diagnostic centres nationwide were collected for culture, identification and drug susceptibility test. Culture positive isolates were tested against streptomycin (S), isoniazid (H), rifampicin (R) and ethambutol (E) using the simplified proportion method and line probe assay (LPA). The LPA was performed in mid-2017. Results: Among 410 samples, 345 positive cultures were obtained and identified as Mycobacterium tuberculosis complex (MTBC). Of the 345 isolates, 133 were further differentiated by GenoType MTBC&reg;as M. tuberculosis, 126 (94.7%) and M. africanum 7 (5.3%). The overall drug resistance patterns were as follows: 43/345 (12.5%), 6/345 (1.7%), 9/345 (2.6%) and 71/345 (20.6%) were resistant to H, R, E and S respectively and 5/345 (1.4%) were multi-drug resistant (MDR). Conclusion: The results indicate high levels of resistance to S and H among new and previously treated TB patients. We recommend adequate surveillance systems including periodic national anti-TB drug resistance surveys.

Low Doses of Rifampicin Used in New Tuberculosis Patients Correlated to Increased Frequency of Rifampicin-Resistance and Poorer Treatment Outcomes

The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.

Tuberculosis of the spine

Pott’s spine,commonly known as spinal tuberculosis(TB),is an extrapulmonary form of TB caused by Mycobacterium TB.Pott’s paraplegia occurs when the spine is involved.Spinal TB is usually caused by the hematogenous spread of infection from a central focus,which can be in the lungs or another location.Spinal TB is distinguished by intervertebral disc involvement caused by the same segmental arterial supply,which can result in severe morbidity even after years of approved therapy.Neurological impairments and spine deformities are caused by progressive damage to the anterior vertebral body.The clinical,radiographic,microbiological,and histological data are used to make the diagnosis of spinal TB.In Pott’s spine,combination multidrug antitubercular therapy is the basis of treatment.The recent appearance of multidrug-resistant/extremely drug-resistant TB and the growth of human immunodeficiency virus infection have presented significant challenges in the battle against TB infection.Patients who come with significant kyphosis or neurological impairments are the only ones who require surgical care.Debride-ment,fusion stabilization,and correction of spinal deformity are the cornerstones of surgical treatment.Clinical results for the treatment of spinal TB are generally quite good with adequate and prompt care.

Prevalence of Mycobacterium tuberculosis Strains Isolated from Both Pulmonary and Extra Pulmonary Samples and Their Resistance to Rifampicin: A Study from Kolkata and Surrounding Suburbs

Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. In India, nearly 1.8 million new cases of TB are reported annually, which accounts for a fifth of new cases in the world—greater than in any other country. Anti-tubercular drugs (ATDs) have been used for decades, and widespread resistance to them is a very serious public health concern in any part of the world. Aim of this study was to determine the prevalence of Rifampicin (the first line Anti-TB drug) resistance among both pulmonary and extra-pulmonary samples tested positive for Mycobacterium tuberculosis and thereby predict the prevalence of Multi-drug resistant (MDR) tuberculosis in Kolkata and its Suburban regions. All 331 randomly collected clinical samples (both Pulmonary and Extra Pulmonary) were initially screened by Zeihl-Neelsen AFB staining followed by culture on BacT/Alert 3D system and on Lowenstein-Jensen medium and the positive samples were subjected to detection of Mycobacterium tuberculosis complex (MTBC) and simultaneous analysis of Rifampicin resistance by Xpert MTB/RIF assay. Out of the 51 (15.40%) culture positive samples, 13.7% of pulmonary samples and 9.09% of extra-pulmonary samples were Rifampicin resistant. The prevalence of Rifampicin resistant TB in our study is high and the possible reasons can be mixing of new as well as retreatment cases and smaller sample size but, yet it can help Government and public health regulatory bodies to formulate adequate strategies to fight against drug resistant tuberculosis, especially in this part of the world.

Mutation Characteristics of inhA and katG Genes in Isoniazid-Resistant Mycobacterium Tuberculosis Patients in Xinjiang

Objective:To analyze the mutation characteristics of inhA and katG genes in isoniazid-resistant Mycobacterium tuberculosis in Xinjiang.Methods:The katG and inhA in 148 strains of isoniazid-resistant Mycobacterium tuberculosis were amplified through fluorescence quantitative PCR,and the amplified products were sequenced and compared.Results:The inhA gene mutation rate of 148 strains of isoniazid-resistant mycobacterium tuberculosis was 13.51%(20/148),among which the inhA gene mutation rate among patients of Han,Uygur,and Kazakh ethnicity were 15.87%,13.21%,and 17.65%,respectively.There was no significant difference in the inhA mutation rate among nationalities(c^(2)=2.897,P>0.05).The mutation rate of the katG gene was 84.46%(125/148),among which the mutation rates of patients of Han,Uyghur,and Kazak ethnicities were 82.54%,84.91%,and 76.47%,respectively.The Hui and other ethnic groups were all affected by the katG gene mutation.There was no significant difference in the mutation rate of the katG gene among different ethnicities(c^(2)=3.772,P>0.05).The mutation rates of the inhA gene in southern Xinjiang,northern Xinjiang,and other provinces were 18.60%,9.28%,and 37.50%,respectively.The mutation rates of the inhA gene in different regions were statistically different(c^(2)=6.381,P<0.05).There was no significant difference in the inhA mutation rate between patients from southern and northern Xinjiang(c^(2)=2.214,P>0.05)and between southern Xinjiang and other provinces(c^(2)=1.424,P>0.05).However,the mutation rate of the inhA gene in patients from other provinces was higher than that in northern Xinjiang(c^(2)=5.539,P<0.05).The mutation rates of the katG gene in southern Xinjiang,northern Xinjiang,and other provinces were 81.40%,87.63%,and 62.50%,respectively.There was no significant difference in the mutation rates of the katG gene among different regions(c^(2)=3.989,P>0.05).Conclusion:katG gene mutation was predominant in isoniazid-resistant tuberculosis patients in Xinjiang Uygur Autonomous Region,and inhA and katG gene mutation were no different among different ethnic groups.

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China

Objective To investigate the prevalence of primary drug-resistant tuberculosis（TB） and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis（MDR-TB）. Methods A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. Results Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75（80.6%） isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65（69.9%） isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine（31.2%） primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531 L rpoB mutation. Conclusion This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.

Clinical Response to Treatment of Central Nervous System Tuberculosis in Non-Human Immunodeficiency Virus-Infected Adolescents and Adults

Introduction: More than half of patients with central nervous system tuberculosis (CNS TB) die or are left with severe neurological deficits despite receiving anti-TB treatment. Aims of the study: This study examined risk factors associated with poor response to initial treatment with four anti-TB drug regimens or three drug regimens with steroids as adjuvant therapy. Methods: This study analyzed medical records from two tertiary hospitals in Busan, Korea, between January 2009 and March 2012. The subjects were non-human immunodeficiency virus (HIV)-infected patients aged ≥16 years with clinical CNS TB. The subjects were divided into two groups according to response to treatment. Results: In totally, 52 patients with CNS TB were included. Of these, 14 (26%) and 38 (73%) showed poor and good responses, respectively. Of the patients with poor response, nine had stage III disease (64.3%) according to the British Medical Research Council (BMRC) staging system. A significantly higher proportion was seen in the good response group (p < 0.05). Patients with positive cerebrospinal fluid (CSF) acid-fast bacillus (AFB) culture, positive sputum AFB culture, positive CSF TB polymerase chain reaction (PCR) results, and brain tuberculoma had poorer responses (p < 0.05). Multivariate analysis to determine risk factors associated with poor response to anti-TB therapy revealed that a poor response was associated with stage III clinical signs upon diagnosis (odds ratio [OR] 32.122;95% confidence interval [CI] 2.221 - 464.605), positive sputum AFB culture (OR 13.624;95% CI 1.066 - 174.149), and tuberculoma on brain images (OR 45.714;95% CI 1.893 - 1104.018). Conclusions: The results demonstrate the importance of identifying the severity of CNS TB and promptly administering anti-TB drugs. It is necessary to perform drug susceptibility testing for anti-TB drugs. Further studies are needed to confirm the correlations between risk factors associated with poor response and anti-TB drug resistance and the other risk factors.

Natural Remedies against Multi-Drug Resistant <i>Mycobacterium tuberculosis</i>

Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications are described for the treatment of TB. Regardless of availability of several drugs to treat TB, the causative agent, M. tuberculosis is nowadays getting resistant toward the conventional drugs and leading to conditions known as Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). This situation has terrified the global health community and raised a demand for new anti-tuberculosis drugs. Medicinal plants have been used to cure different common as well as lethal diseases by ancient civilizations due to its virtue of variety of chemical compounds which may have some important remedial properties. The aim of the present review is to focus the anti-tubercular medicinal plants native to India as well as the plants effective against MDR or XDR-TB across the globe. In the present review, we have addressed 25 medicinal plants for TB and 16 plants effective against MDR-TB testified from India and 23 herbal plants described for MDR-TB across the world during 2011-2015. These herbal plants can serve as promising candidates for developing novel medications to combat multidrug resistant M. tuberculosis.

Drug resistance pattern of Mycobacterium tuberculosis isolates from patients of five provinces of Iran

Objective:To determine the patterns of resistance to first line anti-tuberculosis(TB)drugs among a collection of Mycobacterium tuberculosis(MTB)isolates from 5 provinces of Iran.Methods:A total of the 6 426 clinical specimens from patients suspected of active TB were collected from March 2010 to June 2012.All specimens were subjected for microscopy and culture tests in the TB centers of studies provinces.Drug susceptibility testing to the first line anti-TB drugs for culture positive MTB was performed on Lwenstein-Jensen(LJ)medium using proportion method.Results:Of 6 426 clinical specimens,261 were culture positive for mycobacteria,of which 252 were MTB and 9 were MOTT(mycobacteria other than tuberculosis).Of 252 MTB isolates.211(83.7%)were pan-susceptible and 41(16.3%)were resistant to at least one drug.Resistance was most common to streptomycin.30 isolates(12.0%),followed by isoniuzid,20isolates(8.0%),rifampin,15 isolates(6.0%)and ethambutol,14 isolates(5.5%).Sixteen(6.3%)MTB isolates were MDR.A clear evidence of heterogeneity amongst the 5 provinces in the proportions with resistance to one or more drugs was observed[χ~2=12.209(4 degrees of freedom),P values=0.015 9].Conclusions:The prevalence of drug resistance in this study area underscoring the need for further enforcement of TB control strategies in the Iran.Drug susceptibility testing for all TB cases to provide optimal treatment,establishing advanced diagnostic facilities for rapid detection of MDR-TB and continuous monitoring of drug resistance are recommended for prevention and control of drug-resistant TB.

Adverse Drug Reactions in Patients on Second Line Anti-Tubercular Drugs for Drug Resistant Tuberculosis in Rural Tertiary Care Hospital in North India

Introduction: The adverse drug events (ADEs) to second-line anti-TB drugs are one of the major reasons for the patients default on treatment. A general awareness of various adverse drug events (ADE) and their management is essential for the effective management of tuberculosis. Identification of adverse drug reaction profile of patients can be useful for the early detection, management and prevention of adverse drug events. Material and methods: It was a prospective observational study conducted after approved Institutional Ethics Committee. A total of 104 drug resistant tuberculosis patients registered from 1st November 2012 to 31st October 2013 started with second line anti-tubercular drugs under PMDT-RNCP after taking written informed consent. Adverse drug reaction during treatment recorded and assessed by Hart wig and WHO scale. Results: 87% patients experienced adverse drug reactions. Total 346 ADR were reported. Most common were gastritis (65%) and arthralgia (60.6%), others were nausea (35.6%), vomiting (32.7%), hyperuricemia (30.8%), giddiness (27%), anorexia (17.3), generalized weakness (15.4), insomnia (10.6%), psychosis (8.6%), hearing impairment (6.7%), hypersensitivity reaction (5.8%), peripheral neuropathy (4.8%), visual disturbance (3.8%), nephrotoxicity (2.9%), forgetfulness (2.9%), gynaecomastia (1.9%), hypothyroidism (1%), seizure (1%), and thrombocytopenia (1%). Conclusion: Majority of patients experienced wide range adverse drug reactions. Most of patients faced the problem within 2 - 3 months of initiation of treatment and managed by symptomatic. Early identification, prompt management and standardized reporting adverse drug reactions at all the level of healthcare are needed.

Drug Resistance Trends and Patterns of Mycobacterium Tuberculosis Isolates from Pulmonary Tuberculosis Patients at a Tertiary Care Hospital in Turkey

Background: We aim to determine the proportions and patterns of resistance to first-line drugs: isoniazid (H), rifampicin (R), ethambutol (E) and streptomycin (S) among pulmonary tuberculosis patients. Methods: Strains were obtained from 1584 culture positive pulmonary tuberculosis patients. All specimens were inoculated into L?wenstein-Jensen media (LJ) and TK selective;drug susceptibility tests (DST) were performed for first-line drugs. Results: Multidrug resistant (MDR) were detected in 146 (9.2%) isolates. Three hundred (18.9%) isolates were resistant to H;220 (13.9%) to R;168 (10.6%) to S;137 (8.6%) to E. Any drug resistance was detected in 442 (27.9%) isolates. MDR rate was higher in male patients than females (P = 0.006). MDR rates were different according to the age groups (P = 0.02). The highest rate was in 35 - 44 years and the lowest rate was in 15 - 24 years. Conclusions: We found an association between middle age and male gender and MDR tuberculosis.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

Review: The Molecular Basis of Resistance in <i>Mycobaterium tuberculosis</i>

Tuberculosis is a serious global public health problem and its high prevalence is strongly associated with the increase of drug resistance. This steady increase in the frequency of M. tuberculosis strains resistant to one or more agents commonly used to treat tuberculosis has drawn worldwide attention to understanding the molecular basis of resistance in M. tuberculosis. TB resistance is a great concern in the antibiotic resistance pandemic due to the high risk of death, as patients can remain infected for months or years and also because of the difficulty of the treatment. A molecular understanding of the series of events that render M. tuberculosis multi-drug resistant is very important in order to find a fast and appropriated diagnosis as well as a new target for new drugs.

Tuberculosis treatment-new approach to an old problem

Chronic mycobacterium infections are major causes of disease burden of 20%in a tropical country like India. The inflammatory cascade following these bacterial infections often leads to tissue damage and perpetuates necrosis, fibrosis and the disease process.Pulmonary tuberculosis,multi-drug resistant tuberculosis not only affects individuals but society at large.Current remedial measures using various technology platforms singularly did not produce effective and appreciable reduction in global disease burden.On the contrary,the conventional chemotherapeutic chemical moieties have demonstrated variable pharmacogenomic expression,increased drug resistance,non compliance of strict prolonged drug regimens with debilitating side effects and contraindications. Furthermore,secreted inflammatory cytokines results in chronic infection,immune deviation,and immunopathology in the lungs.Hence,identification of immune escape mechanisms leading to chronic mycobacterial infections is crucial for development of new treatments.The review would dwell into the basic pathogenic mechanism and the newer approaches that may need to be considered for developing novel therapeutic strategies.