Background & Objectives: Emergence of drug resistant Tuberculosis (TB) is a major obstacle in the TB control programme of Bangladesh. This study was carried out to detect pre-extensively drug resistant TB (pre-XDR...Background & Objectives: Emergence of drug resistant Tuberculosis (TB) is a major obstacle in the TB control programme of Bangladesh. This study was carried out to detect pre-extensively drug resistant TB (pre-XDR-TB) cases among the multidrug resistant TB (MDR-TB) patients in Bangladesh, as the early detection of pre-XDR-TB can guide clinicians in the appropriate modification of MDR-TB treatment regimen with effective drugs to prevent treatment failure. Methodology: A total of 68 MDR-TB cases were enrolled in this study. Multiplex Real-time PCR was done to detect pre-XDR-TB cases directly from sputum samples of MDR-TB patients. Results: Out of 68 MDR-TB cases 11 (16.18%) cases were detected as pre-XDR-TB. The resistant profile of the 11 pre-XDR-TB revealed 9 (81.82%) cases of fluoroquinolone (FLQ) resistant pre-XDR-TB and 2 (18.18%) cases of injectable second line (ISL) agent resistant pre-XDR-TB. Out of 11 pre-XDR-TB cases 7 (63.64%) cases had history of taking treatment for MDR-TB regularly, 1 (9.09%) case had history of taking treatment for MDR-TB irregularly and 3 (27.27%) cases had no history of taking treatment for MDR-TB. Conclusion: This study encountered a high rate of pre-XDR-TB cases along with a significant number of primarily resistant bacilli which is of concern in the management of MDR-TB. It is evident that Bangladesh is in urgent need to device strategies for rapid and early detection of pre-XDR-TB in order to prevent treatment failure of MDR-TB cases and also to halt the progression of MDR-TB cases to extensively drug resistant TB (XDR-TB), which is not only difficult but also very expensive to treat.展开更多
We combined the new SensititreTM MYCOTB test with the MODS assay for detection of MDR- and XDR-TB. Categorical agreement of the MODS assay with the critical concentrations at 3 days of incubation was highest for INH (...We combined the new SensititreTM MYCOTB test with the MODS assay for detection of MDR- and XDR-TB. Categorical agreement of the MODS assay with the critical concentrations at 3 days of incubation was highest for INH (91.4%) and RIF (100%) and at 5 days 86.7% and 94.6% for the fluoroquinolones and aminoglycosides, respectively. By combining these two methods, it is possible to identify MDR-TB in as little as 3 days and XDR- or pre-XDR-TB within 5 days.展开更多
Background: Molecular diagnosis based on the detection of mutations conferring genetic drug resistance is useful for early diagnosis and treatment of Pre-XDR and XDR-TB patients. However, the study of mutation as a ma...Background: Molecular diagnosis based on the detection of mutations conferring genetic drug resistance is useful for early diagnosis and treatment of Pre-XDR and XDR-TB patients. However, the study of mutation as a marker to predict Pre-XDR and XDR-TB is rare. Methods: Thirty-four Mycobacterium tuberculosis (MTB) isolates from MDR, Pre-XDR and XDR-TB patients in the upper north of Thailand, who had been identified for drug susceptibility using the indirect agar proportion method from 2005-2012, were examined for genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug resistance, rpoB for rifampicin (RIF) drug resistance, gyrA for ofloxacin (OFX), and rrs for kanamycin (KAN). Associations between resistant genes and Pre-XDR and XDR-TB in the MDR patients were performed using exact probability tests. Univariable logistic regression was used to quantify the strength of association between the gene mutation with Mycobacterium tuberculosis and the prevalence of Pre-XDR and XDR-TB in the MDR patients. Results: The mutations in the region of the rpoB gene at codon 445 (C445T) in the Pre-XDR or XDR-TB patients were significantly 20.6 times more prevalent among the MDR-TB patients. The inhA gene mutation at codon 114 (T114G) was also significantly 8.1 times more prevalent. Conclusion: The findings can be used to predict the odds of Pre-XDR and XDR-TB in MDR-TB patients, as a guide for prevention and treatments.展开更多
在2010年美国、瑞典、以色列、希腊、荷兰、瑞士、澳大利亚等国的一些专家共同提出的关于MDR（multidrug resistant）、XDR（extensively drug resistant）、PDR （pandrug resistant）术语国际标准化建议（草案）的基础（见本刊2011年1...在2010年美国、瑞典、以色列、希腊、荷兰、瑞士、澳大利亚等国的一些专家共同提出的关于MDR（multidrug resistant）、XDR（extensively drug resistant）、PDR （pandrug resistant）术语国际标准化建议（草案）的基础（见本刊2011年10卷3期238-240页）上, Magiorakos等专家于2012年在〈Clinical Microbiology and Infection〉杂志上正式发表了MDR、XDR、PDR耐药菌暂行标准定义.与2010版相比,增加或删除了一些耐药菌判断的代表性抗菌药物,修改了部分肠杆菌科细菌中的固有耐药菌.现将主要部分摘译如下.展开更多
Purpose: The drug resistance pattern in tuberculosis (TB) is still under investigated. We analyzed the clinical data from the patients with smear positive TB and applied the model to predict the patients with smear-po...Purpose: The drug resistance pattern in tuberculosis (TB) is still under investigated. We analyzed the clinical data from the patients with smear positive TB and applied the model to predict the patients with smear-positive TB. Materials and Methods: Medical records information of 6977 cases was included from 11,950 inpatients from January 2009 to November 2013. The cases data were divided into a training set, test set and prediction set. Logistic regression analysis was applied to the training set data to establish a prediction classification model, the effect of which was then evaluated using the test set by receiver operating characteristic (ROC) analysis. The model was then applied to the prediction set to identify incidence of snMDR-TB. Results: Sixteen factors which correlate with MDR-TB-including frequency of hospitalization, province of origin, anti-TB drugs, and complications, were identified from the comparison between SP-TB and spMDR-TB. The area under the ROC curve (AUC) of the prediction model was 0.752 (sensitivity = 61.3%, specificity = 83.3%). The percentage of all inpatients with snMDR-TB (snMDR-TB/Total) was 28.7% ± 0.02%, while that of all SN-PTB with snMDR-TB (snMDR-TB/SN-PTB) was 26.5% ± 0.03%. The ratio of snMDR-TB to MDR-TB (snMDR-TB/MDR-TB) was 2.09 ± 0.33. Conclusion: snMDR-TB as an important source of MDR-TB is a significant hidden problem for MDR-TB control and can be identified by the prediction model. A kind of vicious circle with a certain delay effect exists between snMDR-TB and MDR-TB. To better control MDR-TB, it is necessary to pay greater attention to snMDR-TB, conduct further research and develop targeted therapeutic strategies.展开更多
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 devel...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.展开更多
Background: Extensively drug resistant tuberculosis (XDR-TB) is a serious problem in public health and XDR-TB patients usually develop from multi-drug resistance tuberculosis (MDR-TB) and pre-XDR-TB. The rapid molecul...Background: Extensively drug resistant tuberculosis (XDR-TB) is a serious problem in public health and XDR-TB patients usually develop from multi-drug resistance tuberculosis (MDR-TB) and pre-XDR-TB. The rapid molecular test for drug susceptibility testing (DST) can be used for early detection to prevent XDR-TB. Methods: We examined 34 clinical Mycobacterium tuberculosis (M. tuberculosis) isolates from MDR/XDR-TB patients in the upper north of Thailand that were identified with drug susceptibility profiles by indirect agar proportion method from 2005-2012. Our study investigated the genetic mutations in gyrA for ofloxacin resistance and rrs for kanamycin resistance. The genetic mutations and drug susceptibility test results were analyzed using the exact test. Results: The majority of the ofloxacin resistance was detected in gyrA 21, gyrA 70, gyrA 87, gyrA 102, gyrA 162, and gyrA 187 were at 0%, 12.5%, 37.5%, 0%, 50.0% and 25.0% sensitivity, respectively, and at 96.2, 96.2%, 20.1%, 96.2%, 57.7% and 61.5% specificity, respectively. Kanamycin resistance was found in rrs 512, rrs 241, rrs 223, rrs 414 and rrs 408 at 16.7%, 0%, 0%, 16.7% and 16.7% sensitivity, respectively, and at 96.4%, 92.9%, 82.1%, 82.1% and 71.4% specificity, respectively. This study found no significant correlation between gyrA mutations and ofloxacin resistance and also no correlation between the rrs gene and kanamycin resistance. Conclusion: These primer sequences and PCR products in our study such as gyrA and rrs might be unsuitable to detect ofloxacin and kanamycin resistance in the upper north of Thailand.展开更多
<b>Objective:</b> Almost all year round occurrence of typhoid fever remains a major public health issue in Bangladesh. In recent years, there has been a significant rise in the prevalence of multi-drug res...<b>Objective:</b> Almost all year round occurrence of typhoid fever remains a major public health issue in Bangladesh. In recent years, there has been a significant rise in the prevalence of multi-drug resistance <i>Salmonella typhi</i> in Dhaka city. The major objective of this study was to observe the prevalence of multi-drug and Extended drug-resistant patterns of typhoidal <i>Salmonella typhi</i> among the patients attending a tertiary medical center by conventional culture and serologic test. <b>Materials and Methods:</b> Blood was collected by syringe and equally divided between aerobic & anaerobic BacT Alert bottle, 10 mL for paediatrics. Post isolation <i>Salmonella</i> strains were identified and were tested for antibiotic resistance. <b>Results:</b> A total of 600 blood samples of typhoid suspected patients were tested, where 32.5% came out positive, which were identified as <i>Salmonella typhi</i>. These isolates were susceptible to carbapenem drugs but highly resistant to Fluoroquinolones and Aminoglycosides antibiotics. <b>Discussion:</b> It was seen that 73.23% of isolates among male patients were extensively drug-resistant (XDR) meaning that isolates were sensitive against only one or two antibiotics while in the female it was 58.46%. Isolates from Female patients showed higher multi-drug resistant (MDR) (26.15%) isolates resistance to multiple antibiotics in comparison to isolates from the male (16.54%). 87.19% of the strains showed high drug resistance (XDR and MDR). <b>Conclusion:</b> The emergence of XDR and MDR strains of <i>S. typhi</i> in recent years is becoming a significant threat. Although no PAN-Drug resistance (resistant against all tested drugs) was observed in the current study, a high level of XDR and MDR isolates are indicating that the scenario might take place sooner than later.展开更多
Background: The number of reported MDR-TB cases has been increasing in recent years. Objectives: To describe the epidemiological profile of MDR-TB cases in Bangladesh. Design: This was a descriptive cross-sectional st...Background: The number of reported MDR-TB cases has been increasing in recent years. Objectives: To describe the epidemiological profile of MDR-TB cases in Bangladesh. Design: This was a descriptive cross-sectional study. Settings: The study was conducted among the multi drug resistant tuberculosis patient admitted in the National Institute of Diseases of the Chest and Hospital (NIDCH) Dhaka, Bangladesh. Samples: 148 confirmed cases of MDR-TB. Materials and Methods: Hospital admitted MRD-TB cases were randomly chosen from the above mentioned hospital. Semi-structured and pretested questionnaire were introduced by researcher. Clinical and treatment data i.e. duration of TB drug intake, report of sputum, X-ray and blood test etc. were extracted from the hospital record. Results: Study found, majority of the participants (56.1%) were in the age group of 16 - 30 years. 64.2% of the study subjects were married. Majority of the participants education were whether under primary or primary level. 24.3% participant’s family member and 14.5% of neighbor were having TB. Most common comorbidity were diabetes, pulmonary infection, hearing loss, psychiatric symptoms, chest pain, joint pain etc. 63.5% respondent had high degree of AFB for sputum positivity and more than 98% had positive finding in X-ray chest. On an average ESR was low and also few cases of extremely low ESR were found. 71.6% were under twenty four months regimen. Conclusion: We can conclude that, many possible factors for MDR-TB. There is an urgent need for further study to confirm the exact factors in Bangladesh and address those immediately.展开更多
Background: Tuberculosis remains a very common infectious disease in Democratic Republic of Congo (DRC). The resistance to drugs worsens the prognosis and the outcome of patients affected tuberculosis and increase the...Background: Tuberculosis remains a very common infectious disease in Democratic Republic of Congo (DRC). The resistance to drugs worsens the prognosis and the outcome of patients affected tuberculosis and increase their mortality. Objective: To identify factors associated with death among Multidrugs resistant tuberculosis (MDR/RR TB) patients referred to the referential hospital, Centre d’Excellence Damien (CEDA). Materials and Methods: A retrospective cohort study of patients attending health care to the Center CEDA, a referral center for management of MDR/RR-TB in DR Congo. This study included all MDR/RR-TB patients referred from February 1st, 2015 to February 29th, 2017. A multivariate COX regression was performed to identify factors associated with mortality in the target population. Kaplan Meier method described the survival of patients and the comparison of curves was performed by the test of log Rank. Results: 199 patients were included in our study. Male gender was predominant with a sex ratio of 1.3. The mean age of patients was 35.8 ± 13.9 years. Among them, 18 (15.1%) were died. The major complications were Chronicles pulmonary Heart failure (p = 0.035), Chronic respiratory insufficiency (p = 0.004), depression (p = 0.044), undernutrition (p = 0.033), alcohol addiction (p = 0.006) and high smoking (p = 0.019). In multivariated analysis, factors associated to the death were alcohol addiction (HRa = 12.64, 95% CI 2.36 - 14.55, p = 0.003), asthenia (HRa = 4.75, 95% CI 1.56 - 14.50, p < 0.001), pulmonary consolidation (HRa = 10.01 95% CI 2.34 - 12.86, p = 0.02), some chest X-ray abnormalities such as signs of pulmonary fibrosis (HR = 4.7, 95% CI 2.78 - 28.94, p = 0.002) and the Chronic respiratory insufficiency (HRa = 3.77, 95% CI 1.37 - 10.43, p = 0.010). Conclusion: The present retrospective cohort study revealed that structural and functional pulmonary alteration emerged as the main factors associated with mortality among MDR/RR TB patients in Kinshasa. National Tuberculosis Programs should take into account those parameters while defining mortality reduction strategy.展开更多
Setting: Four decentralised sites are located in rural areas and one centralised hospital in KwaZulu-Natal province, South Africa. Objective: To analyse risk factors associated with multidrug-resistant tuberculosis (M...Setting: Four decentralised sites are located in rural areas and one centralised hospital in KwaZulu-Natal province, South Africa. Objective: To analyse risk factors associated with multidrug-resistant tuberculosis (MDR-TB) using competing risks analysis. Understanding factors associated with MDR-TB and obtaining valid parameter estimates could help in designing control and intervention strategies to lower TB mortality. Method: A prospective study was performed using a competing risk analysis in patients receiving treatment for MDR-TB. The study focused on 1542 patients (aged 18 years and older) who were diagnosed of MDR-TB between July 2008 and June 2010. Time to cure MDR-TB was used as the dependent variable and time to death was the competing risk event. Results: The Fine-Gray regression model indicated that baseline weight was highly significant with sub-distribution hazard ration (SHR) = 1.02, 95% CI: 1.01 - 1.02. This means that weight gain in a month increased chances of curing MDR-TB by 2%. Results show that lower chances to cure MDR-TB were among patients between 41 to 50 years compared to those patients who were between 18 to 30 years old (SHR = 0.80, 95% CI: 0.61 - 1.06). The chances of curing MDR-TB in female patients were low compared to male patients (SHR = 0.84, 95% CI = 0.68 - 1.03), however this was not significant. Furthermore, HIV negative patients had higher chances to cure MDR-TB (SHR = 1.07, 95% CI: 0.85 - 1.35) compared to HIV positive patients. Patients who were treated in the decentralised sites had lower chances to be cured of MDR-TB (SHR = 0.19, 95% CI: 0.07 - 0.54) as compared to patients who were treated in the centralised hospital. Conclusion: Identifying key factors associated with TB and specifying strategies to prevent them can reduce mortality of patients due to TB disease, hence positive treatment outcomes leading to the goal of reducing or end TB deaths. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people with drug-resistant TB.展开更多
文摘Background & Objectives: Emergence of drug resistant Tuberculosis (TB) is a major obstacle in the TB control programme of Bangladesh. This study was carried out to detect pre-extensively drug resistant TB (pre-XDR-TB) cases among the multidrug resistant TB (MDR-TB) patients in Bangladesh, as the early detection of pre-XDR-TB can guide clinicians in the appropriate modification of MDR-TB treatment regimen with effective drugs to prevent treatment failure. Methodology: A total of 68 MDR-TB cases were enrolled in this study. Multiplex Real-time PCR was done to detect pre-XDR-TB cases directly from sputum samples of MDR-TB patients. Results: Out of 68 MDR-TB cases 11 (16.18%) cases were detected as pre-XDR-TB. The resistant profile of the 11 pre-XDR-TB revealed 9 (81.82%) cases of fluoroquinolone (FLQ) resistant pre-XDR-TB and 2 (18.18%) cases of injectable second line (ISL) agent resistant pre-XDR-TB. Out of 11 pre-XDR-TB cases 7 (63.64%) cases had history of taking treatment for MDR-TB regularly, 1 (9.09%) case had history of taking treatment for MDR-TB irregularly and 3 (27.27%) cases had no history of taking treatment for MDR-TB. Conclusion: This study encountered a high rate of pre-XDR-TB cases along with a significant number of primarily resistant bacilli which is of concern in the management of MDR-TB. It is evident that Bangladesh is in urgent need to device strategies for rapid and early detection of pre-XDR-TB in order to prevent treatment failure of MDR-TB cases and also to halt the progression of MDR-TB cases to extensively drug resistant TB (XDR-TB), which is not only difficult but also very expensive to treat.
文摘We combined the new SensititreTM MYCOTB test with the MODS assay for detection of MDR- and XDR-TB. Categorical agreement of the MODS assay with the critical concentrations at 3 days of incubation was highest for INH (91.4%) and RIF (100%) and at 5 days 86.7% and 94.6% for the fluoroquinolones and aminoglycosides, respectively. By combining these two methods, it is possible to identify MDR-TB in as little as 3 days and XDR- or pre-XDR-TB within 5 days.
文摘Background: Molecular diagnosis based on the detection of mutations conferring genetic drug resistance is useful for early diagnosis and treatment of Pre-XDR and XDR-TB patients. However, the study of mutation as a marker to predict Pre-XDR and XDR-TB is rare. Methods: Thirty-four Mycobacterium tuberculosis (MTB) isolates from MDR, Pre-XDR and XDR-TB patients in the upper north of Thailand, who had been identified for drug susceptibility using the indirect agar proportion method from 2005-2012, were examined for genetic site mutations of katG, inhA, and ahpC for isoniazid (INH) drug resistance, rpoB for rifampicin (RIF) drug resistance, gyrA for ofloxacin (OFX), and rrs for kanamycin (KAN). Associations between resistant genes and Pre-XDR and XDR-TB in the MDR patients were performed using exact probability tests. Univariable logistic regression was used to quantify the strength of association between the gene mutation with Mycobacterium tuberculosis and the prevalence of Pre-XDR and XDR-TB in the MDR patients. Results: The mutations in the region of the rpoB gene at codon 445 (C445T) in the Pre-XDR or XDR-TB patients were significantly 20.6 times more prevalent among the MDR-TB patients. The inhA gene mutation at codon 114 (T114G) was also significantly 8.1 times more prevalent. Conclusion: The findings can be used to predict the odds of Pre-XDR and XDR-TB in MDR-TB patients, as a guide for prevention and treatments.
文摘在2010年美国、瑞典、以色列、希腊、荷兰、瑞士、澳大利亚等国的一些专家共同提出的关于MDR（multidrug resistant）、XDR（extensively drug resistant）、PDR （pandrug resistant）术语国际标准化建议（草案）的基础（见本刊2011年10卷3期238-240页）上, Magiorakos等专家于2012年在〈Clinical Microbiology and Infection〉杂志上正式发表了MDR、XDR、PDR耐药菌暂行标准定义.与2010版相比,增加或删除了一些耐药菌判断的代表性抗菌药物,修改了部分肠杆菌科细菌中的固有耐药菌.现将主要部分摘译如下.
文摘Purpose: The drug resistance pattern in tuberculosis (TB) is still under investigated. We analyzed the clinical data from the patients with smear positive TB and applied the model to predict the patients with smear-positive TB. Materials and Methods: Medical records information of 6977 cases was included from 11,950 inpatients from January 2009 to November 2013. The cases data were divided into a training set, test set and prediction set. Logistic regression analysis was applied to the training set data to establish a prediction classification model, the effect of which was then evaluated using the test set by receiver operating characteristic (ROC) analysis. The model was then applied to the prediction set to identify incidence of snMDR-TB. Results: Sixteen factors which correlate with MDR-TB-including frequency of hospitalization, province of origin, anti-TB drugs, and complications, were identified from the comparison between SP-TB and spMDR-TB. The area under the ROC curve (AUC) of the prediction model was 0.752 (sensitivity = 61.3%, specificity = 83.3%). The percentage of all inpatients with snMDR-TB (snMDR-TB/Total) was 28.7% ± 0.02%, while that of all SN-PTB with snMDR-TB (snMDR-TB/SN-PTB) was 26.5% ± 0.03%. The ratio of snMDR-TB to MDR-TB (snMDR-TB/MDR-TB) was 2.09 ± 0.33. Conclusion: snMDR-TB as an important source of MDR-TB is a significant hidden problem for MDR-TB control and can be identified by the prediction model. A kind of vicious circle with a certain delay effect exists between snMDR-TB and MDR-TB. To better control MDR-TB, it is necessary to pay greater attention to snMDR-TB, conduct further research and develop targeted therapeutic strategies.
文摘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.
文摘Background: Extensively drug resistant tuberculosis (XDR-TB) is a serious problem in public health and XDR-TB patients usually develop from multi-drug resistance tuberculosis (MDR-TB) and pre-XDR-TB. The rapid molecular test for drug susceptibility testing (DST) can be used for early detection to prevent XDR-TB. Methods: We examined 34 clinical Mycobacterium tuberculosis (M. tuberculosis) isolates from MDR/XDR-TB patients in the upper north of Thailand that were identified with drug susceptibility profiles by indirect agar proportion method from 2005-2012. Our study investigated the genetic mutations in gyrA for ofloxacin resistance and rrs for kanamycin resistance. The genetic mutations and drug susceptibility test results were analyzed using the exact test. Results: The majority of the ofloxacin resistance was detected in gyrA 21, gyrA 70, gyrA 87, gyrA 102, gyrA 162, and gyrA 187 were at 0%, 12.5%, 37.5%, 0%, 50.0% and 25.0% sensitivity, respectively, and at 96.2, 96.2%, 20.1%, 96.2%, 57.7% and 61.5% specificity, respectively. Kanamycin resistance was found in rrs 512, rrs 241, rrs 223, rrs 414 and rrs 408 at 16.7%, 0%, 0%, 16.7% and 16.7% sensitivity, respectively, and at 96.4%, 92.9%, 82.1%, 82.1% and 71.4% specificity, respectively. This study found no significant correlation between gyrA mutations and ofloxacin resistance and also no correlation between the rrs gene and kanamycin resistance. Conclusion: These primer sequences and PCR products in our study such as gyrA and rrs might be unsuitable to detect ofloxacin and kanamycin resistance in the upper north of Thailand.
文摘<b>Objective:</b> Almost all year round occurrence of typhoid fever remains a major public health issue in Bangladesh. In recent years, there has been a significant rise in the prevalence of multi-drug resistance <i>Salmonella typhi</i> in Dhaka city. The major objective of this study was to observe the prevalence of multi-drug and Extended drug-resistant patterns of typhoidal <i>Salmonella typhi</i> among the patients attending a tertiary medical center by conventional culture and serologic test. <b>Materials and Methods:</b> Blood was collected by syringe and equally divided between aerobic & anaerobic BacT Alert bottle, 10 mL for paediatrics. Post isolation <i>Salmonella</i> strains were identified and were tested for antibiotic resistance. <b>Results:</b> A total of 600 blood samples of typhoid suspected patients were tested, where 32.5% came out positive, which were identified as <i>Salmonella typhi</i>. These isolates were susceptible to carbapenem drugs but highly resistant to Fluoroquinolones and Aminoglycosides antibiotics. <b>Discussion:</b> It was seen that 73.23% of isolates among male patients were extensively drug-resistant (XDR) meaning that isolates were sensitive against only one or two antibiotics while in the female it was 58.46%. Isolates from Female patients showed higher multi-drug resistant (MDR) (26.15%) isolates resistance to multiple antibiotics in comparison to isolates from the male (16.54%). 87.19% of the strains showed high drug resistance (XDR and MDR). <b>Conclusion:</b> The emergence of XDR and MDR strains of <i>S. typhi</i> in recent years is becoming a significant threat. Although no PAN-Drug resistance (resistant against all tested drugs) was observed in the current study, a high level of XDR and MDR isolates are indicating that the scenario might take place sooner than later.
文摘Background: The number of reported MDR-TB cases has been increasing in recent years. Objectives: To describe the epidemiological profile of MDR-TB cases in Bangladesh. Design: This was a descriptive cross-sectional study. Settings: The study was conducted among the multi drug resistant tuberculosis patient admitted in the National Institute of Diseases of the Chest and Hospital (NIDCH) Dhaka, Bangladesh. Samples: 148 confirmed cases of MDR-TB. Materials and Methods: Hospital admitted MRD-TB cases were randomly chosen from the above mentioned hospital. Semi-structured and pretested questionnaire were introduced by researcher. Clinical and treatment data i.e. duration of TB drug intake, report of sputum, X-ray and blood test etc. were extracted from the hospital record. Results: Study found, majority of the participants (56.1%) were in the age group of 16 - 30 years. 64.2% of the study subjects were married. Majority of the participants education were whether under primary or primary level. 24.3% participant’s family member and 14.5% of neighbor were having TB. Most common comorbidity were diabetes, pulmonary infection, hearing loss, psychiatric symptoms, chest pain, joint pain etc. 63.5% respondent had high degree of AFB for sputum positivity and more than 98% had positive finding in X-ray chest. On an average ESR was low and also few cases of extremely low ESR were found. 71.6% were under twenty four months regimen. Conclusion: We can conclude that, many possible factors for MDR-TB. There is an urgent need for further study to confirm the exact factors in Bangladesh and address those immediately.
文摘Background: Tuberculosis remains a very common infectious disease in Democratic Republic of Congo (DRC). The resistance to drugs worsens the prognosis and the outcome of patients affected tuberculosis and increase their mortality. Objective: To identify factors associated with death among Multidrugs resistant tuberculosis (MDR/RR TB) patients referred to the referential hospital, Centre d’Excellence Damien (CEDA). Materials and Methods: A retrospective cohort study of patients attending health care to the Center CEDA, a referral center for management of MDR/RR-TB in DR Congo. This study included all MDR/RR-TB patients referred from February 1st, 2015 to February 29th, 2017. A multivariate COX regression was performed to identify factors associated with mortality in the target population. Kaplan Meier method described the survival of patients and the comparison of curves was performed by the test of log Rank. Results: 199 patients were included in our study. Male gender was predominant with a sex ratio of 1.3. The mean age of patients was 35.8 ± 13.9 years. Among them, 18 (15.1%) were died. The major complications were Chronicles pulmonary Heart failure (p = 0.035), Chronic respiratory insufficiency (p = 0.004), depression (p = 0.044), undernutrition (p = 0.033), alcohol addiction (p = 0.006) and high smoking (p = 0.019). In multivariated analysis, factors associated to the death were alcohol addiction (HRa = 12.64, 95% CI 2.36 - 14.55, p = 0.003), asthenia (HRa = 4.75, 95% CI 1.56 - 14.50, p < 0.001), pulmonary consolidation (HRa = 10.01 95% CI 2.34 - 12.86, p = 0.02), some chest X-ray abnormalities such as signs of pulmonary fibrosis (HR = 4.7, 95% CI 2.78 - 28.94, p = 0.002) and the Chronic respiratory insufficiency (HRa = 3.77, 95% CI 1.37 - 10.43, p = 0.010). Conclusion: The present retrospective cohort study revealed that structural and functional pulmonary alteration emerged as the main factors associated with mortality among MDR/RR TB patients in Kinshasa. National Tuberculosis Programs should take into account those parameters while defining mortality reduction strategy.
文摘Setting: Four decentralised sites are located in rural areas and one centralised hospital in KwaZulu-Natal province, South Africa. Objective: To analyse risk factors associated with multidrug-resistant tuberculosis (MDR-TB) using competing risks analysis. Understanding factors associated with MDR-TB and obtaining valid parameter estimates could help in designing control and intervention strategies to lower TB mortality. Method: A prospective study was performed using a competing risk analysis in patients receiving treatment for MDR-TB. The study focused on 1542 patients (aged 18 years and older) who were diagnosed of MDR-TB between July 2008 and June 2010. Time to cure MDR-TB was used as the dependent variable and time to death was the competing risk event. Results: The Fine-Gray regression model indicated that baseline weight was highly significant with sub-distribution hazard ration (SHR) = 1.02, 95% CI: 1.01 - 1.02. This means that weight gain in a month increased chances of curing MDR-TB by 2%. Results show that lower chances to cure MDR-TB were among patients between 41 to 50 years compared to those patients who were between 18 to 30 years old (SHR = 0.80, 95% CI: 0.61 - 1.06). The chances of curing MDR-TB in female patients were low compared to male patients (SHR = 0.84, 95% CI = 0.68 - 1.03), however this was not significant. Furthermore, HIV negative patients had higher chances to cure MDR-TB (SHR = 1.07, 95% CI: 0.85 - 1.35) compared to HIV positive patients. Patients who were treated in the decentralised sites had lower chances to be cured of MDR-TB (SHR = 0.19, 95% CI: 0.07 - 0.54) as compared to patients who were treated in the centralised hospital. Conclusion: Identifying key factors associated with TB and specifying strategies to prevent them can reduce mortality of patients due to TB disease, hence positive treatment outcomes leading to the goal of reducing or end TB deaths. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people with drug-resistant TB.
