Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-spe...Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.展开更多
Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection mice.Methods:BALB/c mice were used as experimental ...Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection mice.Methods:BALB/c mice were used as experimental animals,multidrug-resistant Mycobacterium tuberculosis infection models were built,randomly divided into model group,moxifloxacin group,thymopentin group and combined treatment group and given corresponding drug intervention,and then colony numbers in the spleen and lung,T lymphocyte subset contents and programmed death-1(PD-1) expression levels in peripheral blood were detected.Results:Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group:contents of CD3^+CD4^+T cells,Thl and Thl7 in peripheral blood of moxifloxacin group and thymopentin group were higher than dtose of model group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of model group;contents of CD3^+CD4^+T cells.Th 1 and Th 17 in peripheral blood of combined treatment group were higher than those of moxifloxacin group and thymopentin group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of moxifloxacin group and thymopentin group:PD-I expression levels on T lymphocyte,B lymphocyte and monocyte surface in peripheral blood of moxifloxacin group and thymopentin group were lower than those of model group,and PD-I expression levels on T lymphocyte.B lymphocyte and monocyte surface in peripheral blood of combined treatment group were lower than those of moxifloxacin group and thymopentin group.Conclusions:Immune formulation thymopentin can enhance the anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice,decrease bacterial load in lung and spleen,and enhance immune function.展开更多
We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. ...We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment;the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on antiretroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted.展开更多
Background:Tuberculosis remains a major public-health problem in the world, despite several efforts to improve case identification and treatment. Particularly multidrug-resistant tuberculosis is becoming a major threa...Background:Tuberculosis remains a major public-health problem in the world, despite several efforts to improve case identification and treatment. Particularly multidrug-resistant tuberculosis is becoming a major threat to tuberculosis control programs in Ethiopia which seriously threatens the control and prevention efforts and is associated with both high death rates and treatment costs. Methods: A case-control study was conducted to assess risk factors and characteristics of MDR-TB cases at ALERT Hospital, Addis Ababa, Ethiopia, where cases were 167 MDR-TB patients, while controls were newly diagnosed and bacteriologically confirmed pulmonary TB cases of similar number, who were matched by sex and age of 5-years interval. Results: The socio-demographic characteristics of the participants indicated that majority (53.3%) were males and 46.7% females;a little over half of cases (55.1%) were in the age group 26 - 45 years, whereas 46.7% of controls were in this age group. According to the multivariable logistic regression analysis, previous history of hospital admission was the only factor that was identified as predictor which increased risk to develop MDR-TB by almost twenty times (AOR = 19.5;95% CI: 9.17 - 41.62) and P-value of <0.05. All other studied factor such as being unemployed, family size, having member of household member with TB, and history of visiting hospital in past 12 months etc., didn’t show any statistically significant association. Conclusion: The study identified previous history of hospital admission as independent predictors for the occurrence of MDR-TB, while other studied variables didn’t show any strong association. The findings added to the pool of knowledge emphasizing the need for instituting strong infection control practice at health care facilities to prevent nosocomial transmission of MDR-TB.展开更多
Multidrug resistant tuberculosis (MDR-TB) is an emerging challenge for TB control programs globally. Ethiopia ranks 7<sup>th</sup> among the world’s 22 high TB burden countries. According to report of WHO...Multidrug resistant tuberculosis (MDR-TB) is an emerging challenge for TB control programs globally. Ethiopia ranks 7<sup>th</sup> among the world’s 22 high TB burden countries. According to report of WHO (2017), TB is one of the leading infectious causes of death in Ethiopia claiming the life of more than 30 thousand people annually. The surge of MDR-TB has been compounding the problem further. Facility-based MDR-TB researches have not been generated in equal pace with community-based ones. The aim of this study was to assess the prevalence of MDR-TB using clinical records of MDR-TB patients in Adama Hospital Medical College (AHMC) from 2014 to 2018. All clinical data of MDR-TB from 2014-2018 was collected from AHMC TB department. Socio-demographic and risk factor data were collected from patients using semi-structured questionnaire. Data were analyzed using Microsoft excel and SPSS version 20. Out of a total 2332 TB suspected cases admitted to AHMC from 2014 to 2018, 175 (7.5%) were confirmed MDR-TB cases or confirmed Rifampicin resistant cases. In particular, 97 (4.2%) presented presumptive MDR-TB alone and 78 (3.3%) showed confirmed Rifampicin resistance alone. Comparison among age groups showed the highest prevalence for 24 - 44 years with 1.8% and 1.5% confirmed MDR-TB and Rifampicin resistance. The overall prevalence of MDR-TB was moderate indicating for possible rise of the problem due to course of time. Further study combining both community and health facility based is recommended to highlight the need to make useful strategies for testing, surveillance and effective clinical management of MDR-TB cases.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
Objective:To systematically review the influencing factors of the treatment outcome of multidrug-resistant pulmonary tuberculosis and provide reference for the prevention and treatment of multidrug-resistant pulmonary...Objective:To systematically review the influencing factors of the treatment outcome of multidrug-resistant pulmonary tuberculosis and provide reference for the prevention and treatment of multidrug-resistant pulmonary tuberculosis.Method:Case control studies on the factors influencing the treatment outcome of multidrug-resistant pulmonary tuberculosis in Chinese databases(CNKI,VIP,Wanfang,Sinomed)and English databases(Pubmed,Web of science,Medline,Embase,Scopus)were searched and collected by computer.The search period was from the establishment of the database to January 2023.After screening and quality evaluation,RevMan5.4 was used for meta-analysis.Result:Totally 18 articles were ultimately included,with a sample size of 7328 people.The results showed that retreatment,complications,adverse reactions,and gender were related to the treatment outcome of multidrug-resistant pulmonary tuberculosis.The OR values and 95%CI of each factor were 0.22(0.17-0.29),0.38(0.32-0.46),0.27(0.17-0.44),and 0.43(0.33-0.56),respectively.Conclusion:Complications,retreatment,adverse reactions,and male gender are effective risk factors for the treatment outcome of multidrug-resistant pulmonary tuberculosis.In clinical practice,more targeted measures are needed for different types of patients.Due to the limitations of the number of studies,the above conclusions require more research to support them.展开更多
Background: For countries with limited resources such as the Democratic Republic of the Congo (DRC), the diagnosis of Multidrug-resistant tuberculosis (MDR-TB) is still insufficient. The MDR-TB identification is done ...Background: For countries with limited resources such as the Democratic Republic of the Congo (DRC), the diagnosis of Multidrug-resistant tuberculosis (MDR-TB) is still insufficient. The MDR-TB identification is done primarily among at-risk groups. The knowledge of the true extent of the MDR-TB remains a major challenge. This study tries to determine the proportion of MDR-TB in each group of presumptive MDR-TB patients and to identify some associated factors. Methods: This is an analysis of the DRC surveillance between 2007 and 2016. The proportions were expressed in Percentage. The logistic regression permits to identify the associated factors with the RR-/MDR-TB with adjusted Odds-ratio and 95% CI. Significance defined as p ≤ 0.05. Results: Overall, 83% (5407/6512) of the MDR-TB presumptive cases had each a TB test. 86.5% (4676/5407) had each a culture and drug sensitive testing (DST) on solid medium, and 24.3% (1312/5407) had performed an Xpert MTB/RIF test. The proportion of those with at least one first-line drug resistance was 59.3% [95% CI 57.2 - 61.4] among which 50.1%, [95% CI 47.9 - 52.3] for the isoniazid, 45.6% [95% CI 43.4 - 47.8] for the rifampicin, 49.9% [95% CI 47.8 - 52.1] for ethambutol and 35.8% [95% CI 33.7 - 37.9] for streptomycin. The confirmation of MDR-TB was 42.8% [95% CI 38.4 - 47.8]. Combining both tests, the proportion of RR-/MDR-TB was 49.6% [95% CI 47.9 - 51.4] for all presumptives. This proportion was 60.0% for failures, 40.7% for relapses and 34.7% for defaulters. Associated factors with the diagnosis of MDR-TB were: aged less than 35 years;prior treatment failure;defaulters;the delay between the collection of sputum and the test completion. Conclusion: The proportion of RR-/MDR-TB among the presumptives has been higher than those estimated generally. The National tuberculosis programme (NTP) should improve patient follow-up to reduce TB treatment failures and defaulting. Moreover, while increasing the use of molecular tests, they should reduce sample delivery times when they use culture and DST concomitantly.展开更多
Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. B...Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. Because of the ototoxic effects of AGs, the World Health Organization (WHO) has recommended the introduction of the bedaquiline regimen. However, very few data are available regarding the susceptibility of bedaquiline to induce hearing loss, hence the present study set out to compare the AG-based regimen and the bedaquiline-based regimen in the occurrence of hearing loss in MDR-TB patients. Methods: This is a prospective multicenter cohort study that included 335 MDR-TB patients, performed in Kinshasa (DRC) during the period from January 2020 to January 2021. Sociodemographic, clinical, biological and audiometric data were analyzed using Stata 17. Repeated-measures analysis of variance was used to compare changes in the degree of hearing loss over time between the two groups of patients on AG and bedaquiline regimens. The double-difference method was estimated using regression with fixed-effects. A p value < 0.05 was considered the threshold for statistical significance. Results: The degree of hearing loss was similar between the two groups at the first month [AGs (28 dB) vs BDQ (30 dB);p = 0.298]. At six months, the mean degree of hearing loss was significantly greater in the aminoglycoside regimen group [AGs (60.5 dB) vs BDQ (44 dB);p < 0.001]. The double difference was significant, with a greater increase in hearing loss in the AGs group (diff-in-diff 18.3;p < 0.001). After adjustment for age and serum albumin, the group receiving the AG-based regimen had a 2-point greater worsening than those with bedaquiline at the sixth month (diff-in-diff 19.8;p Conclusion: Hearing loss is frequent with both treatment regimens, but more marked with the Aminoglycoside-based regimen. Thus, bedaquiline should also benefit for audiometric monitoring in future MDR-TB patients.展开更多
Revised national tuberculosis control programme in India has limited co-hort-wise information about what happens to patients diagnosed with multidrug resistant TB (MDR-TB). We determined the pre-treatment loss to foll...Revised national tuberculosis control programme in India has limited co-hort-wise information about what happens to patients diagnosed with multidrug resistant TB (MDR-TB). We determined the pre-treatment loss to follow-up (non-initiation of treatment by programme within 6 months of diagnosis) and time from diagnosis to treatment initiation in Bhopal district, central India (2014). Pre-treatment loss to follow-up was 13% (0.95 CI: 7%, 23%), not significantly different from the national estimates (18%) and median time to initiate treatment was seven days, lower than that reported elsewhere in the country. Bhopal was performing well with reference to time to treatment initiation in programmatic settings.展开更多
Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic...Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic sensorineural hearing loss. Research on risk factors is essential to enable high-risk individuals to benefit from preventive measures in settings with limited resources. Objective: This study aimed to assess the determinants of the hearing loss in patients with MDR-TB. Methods: This prospective multicenter cohort study included 337 patients with MDR-TB. It was performed in Kinshasa (Democratic Republic of the Congo) between January 2020 and January 2021. Sociodemographic, clinical, biological, therapeutic, and audiometric data were exported and analyzed using Stata 17 and MedCalc. The fixed-effect linear regression panel model was used to assess the degree of the hearing loss over time according to the following covariates: therapeutic regimen (aminoglycosides, bedaquiline, or alternate), stage of chronic kidney disease (CKD), age at inclusion, body mass index, serum albumin level, HIV status, alcohol intake, hypertension, and hemoglobin level. The Hausman test was used to select between fixed- and random-effect estimators. The threshold for statistical significance was set at p Result: A total of 236 patients (70%) received an aminoglycoside-based regimen, 61 (18%) received a bedaquiline-based regimen, and 40 (12%) received aminoglycosides relayed by bedaquiline. The frequency of the hearing loss increased from 62% to 96.3% within six months for all therapeutic regimens. The Hearing loss worsened, with moderate (72.4%) and profound (16%) deafness being predominant. An Exposure to the treatment for more than one month (β coeff: 27.695, Se: 0.793, p β coeff: 6.102, Se: 1.779, p β coeff: 5.610, Se: 1.682, p = 0.001), and an eGFR β coeff: 6.730, Se: 2.70, p = 0.013) were the independent risk factors associated with the hearing loss in patients with MDR-TB. Conclusions: The Hearing loss was more prevalent and worsened during the treatment of the patients with MDR-TB. An Exposure for more than one month, AG-based regimens, advanced age, hypoalbuminemia, and CKD have emerged as the main determinants of the worsening of the hearing loss.展开更多
AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, labor...AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm<sup>3</sup>. In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.展开更多
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 eff...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.展开更多
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 exte...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.展开更多
Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis (MDR-TB) remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patien...Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis (MDR-TB) remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. Methods We used 12-locus mycobactedal interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects' medical records. Results All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR (DTM-PCR) identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit (MIRU) pattern (232225172531) and the same MIRU pattern (3677235). Strains from family-2 had the same MIRU pattern (2212261553323) and the same MIRU pattern (3685134). Strains from family-3 did not have the same MIRU pattern and they differed at only one locus (223326173533, 223325173533), and did not have the same VNTR pattern with two locus differed (3667233, 3677234). Conclusions Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a familv. Household tuberculosis transmission could be prevented with adequate treatment of source Patients.展开更多
Background:Multidrug drug resistant Tuberculosis(MDR-TB)and extensively drug resistant Tuberculosis(XDR-TB)have emerged as significant public health threats worldwide.This systematic review and meta-analysis aimed to ...Background:Multidrug drug resistant Tuberculosis(MDR-TB)and extensively drug resistant Tuberculosis(XDR-TB)have emerged as significant public health threats worldwide.This systematic review and meta-analysis aimed to investigate the effects of community-based treatment to traditional hospitalization in improving treatment success rates among MDR-TB and XDR-TB patients in the 27 MDR-TB High burden countries(HBC).Methods:We searched PubMed,Cochrane,Lancet,Web of Science,International Journal of Tuberculosis and Lung Disease,and Centre for Reviews and Dissemination(CRD)for studies on community-based treatment and traditional hospitalization and MDR-TB and XDR-TB from the 27 MDR-TB HBC.Data on treatment success and failure rates were extracted from retrospective and prospective cohort studies,and a case control study.Sensitivity analysis,subgroup analyses,and meta-regression analysis were used to explore bias and potential sources of heterogeneity.Results:The final sample included 16 studies involving 3344 patients from nine countries;Bangladesh,China,Ethiopia,Kenya,India,South Africa,Philippines,Russia,and Uzbekistan.Based on a random-effects model,we observed a higher treatment success rate in community-based treatment(Point estimate=0.68,95%CI:0.59 to 0.76,p<0.01)compared to traditional hospitalization(Point estimate=0.57,95%CI:0.44 to 0.69,p<0.01).A lower treatment failure rate was observed in community-based treatment 7%(Point estimate=0.07,95%CI:0.03 to 0.10;p<0.01)compared to traditional hospitalization(Point estimate=0.188,95%CI:0.10 to 0.28;p<0.01).In the subgroup analysis,studies without HIV co-infected patients,directly observed therapy short course-plus(DOTS-Plus)implemented throughout therapy,treatment duration>18 months,and regimen with drugs>5 reported higher treatment success rate.In the meta-regression model,age of patients,adverse events,treatment duration,and lost to follow up explains some of the heterogeneity of treatment effects between studies.Conclusion:Community-based management improved treatment outcomes.A mix of interventions with DOTSPlus throughout therapy and treatment duration>18 months as well as strategies in place for lost to follow up and adverse events should be considered in MDR-TB and XDR-TB interventions,as they influenced positively,treatment success.展开更多
Objective To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Methods Biapenem/clavulanate(BP/CL) was evaluated for in vitro activity against Myc...Objective To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Methods Biapenem/clavulanate(BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis(Mtb) multidrug-resistant(MDR) isolates, extensively drug-resistant(XDR) isolates, and the H37 RV strain. BP/CL activity against the H37 Rv strain was assessed in liquid cultures, in macrophages, and in mice. Results BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units(CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment(isoniazid + rifampin + pyrazinamide) after 2 months of treatment. Conclusion BP/CL may provide a new option to clinically treat MDR tuberculosis.展开更多
Background: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in Coastal region. This...Background: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in Coastal region. This is a major challenge in tuberculosis control. Diagnosis is based on Ziel-Neelsen staining alone and patients are treated without information on sensitivity patterns. Aim: This study aimed to determine drug susceptibility patterns of Mycobacterium tuberculosis in Coastal Kenya. Study Design: Hospital and laboratory based cross-sectional study was carried between April 2015 and July 2016 at Coast General Referral hospital;Tudor, Port-Reitz, Likoni Sub-County hospitals;Mlaleo, Kongowea and Mikindani health centers. Methodology: Sputum samples from patients with bacteriological confirmed TB on microscopy were cultured on Lowenstein Jensen (LJ) media. Strains of MTB complex from Lowenstein Jensen (LJ) slopes were subjected to drug susceptibility testing (DST) to first-line drugs including isoniazid (H), rifampicin (R), streptomycin (S) and Ethambutol (E) using proportional method on the Mycobacterium Growth Indicator Tube (MGIT) conventional method. Participants were offered diagnostic testing and counselling for HIV testing. Results: Drug sensitivity test was performed for a total of 210 Mycobacterium tuberculosis isolates for the first line anti-TB drugs. About seventy eight percent and twenty nine percent of the strains from new patients and previously treated patients were fully sensitive to all the drugs tested respectively. Prevalence of any resistance to one drug was 102 (48.6%, 95% CI: 20.45 - 28.23). Any single drug resistance was most frequent in isoniazid 30 (16.0%), Ethambutol 20 (10.0%), Streptomycin 18 (18.3%) and Rifampicin 4 (2.1%) in newly diagnosed patients. Among previously treated patients any resistance to streptomycin, ethambutol, isoniaziad and rifampicin was 10 (58.8%), 9 (52.9%), 7 (41.2%) and 4 (23.5%) respectively. Prevalence of MDR-TB defined as resistant to at least both isoniazid and rifampicin was 10 (4.8%) among new and previously treated patients respectively. Conclusion: The current study reveals that the overall resistance to first line anti-TB drugs was high. Although the rate of MDR-TB was relatively low, this signifies that conditions favouring the spread of MDR-TB are on high rise. Therefore, it is essential to address the problems of development of drug re-sistant strains of TB by establishing good TB programmes (DOTS). Patients’ adherence to anti-TB drugs and introducing drug sensitivity testing (DST) services at County level hospitals will minimize occurrence of drug resistant.展开更多
<b><span>Introduction:</span></b><span></span><b> </b><span>Multidrug</span><span><span><span style="font-family:;" "="&qu...<b><span>Introduction:</span></b><span></span><b> </b><span>Multidrug</span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span>resistant tuberculosis (MDR-TB) is treated with second</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "=""><span>line antituberculosis drugs. These drugs are notorious for inflicting serious adverse drug reactions (ADRs), which many studies have shown causes a wide range of economic and health problems including death. <b></b></span><b><b><span>Aim:</span></b><span></span></b></span><b> </b><span>The study examined the prevalence of ADRs, associated risk factors, socio</span></span></span><span><span><span>-</span></span></span><span><span><span style="font-family:;" "=""><span>demographic association and outcomes among patients treated for MDR-TB at a comprehensive tuberculosis treatment center in Nigeria. <b></b></span><b><b><span>Method:</span></b><span></span></b> The study was conducted at the Government Chest Hospital, Jericho, Ibadan. We applied a </span></span></span><span><span><span>retrospective </span></span></span><span><span><span>assessment of patient treatment data and ADRs reports stored at the study site from March 2013 and February 2016. Subsequently, a prospective study of ADRs was conducted on patients admitted into the same hospital. Causality relationship between the drugs and the reported ADRs was determined with a special</span></span></span><span><span><span>l</span></span></span><span><span><span>y validated</span></span></span><span><span><span> tool. The outcomes assessed include recovery from the ADRs, death </span></span></span><span><span><span>and</span></span></span><span><span><span style="font-family:;" "=""><span> permanent deafness from the ADRs. Extracted data were analyzed using SPSS version 22.0. Risk Ratio was calculated for the influence of risk factors for adverse drug reactions. Logistic regression was performed to test for the strength of relationships between risk factors and incidence of ADRs among patients. <b></b></span><b><b><span>Result:</span></b><span></span></b> Almost all the participants in this study reported adverse drug reaction [99% (118/119)]. However, ototoxicity was the most prevalent ADR (35.3%), followed by electrolyte imbalance (12.6%)</span></span></span><span><span><span>,</span></span></span><span><span><span> gastrointestinal track (10.1%) and psychiatric disorders (10.1%). Being older than 35 years and HIV negative or having a healthy BMI were not significant risk factors for developing ADRs. </span></span></span><span><span><span>D</span></span></span><span><span><span style="font-family:;" "=""><span>uration of ADR above one month was significantly associated with the outcome of ADR. <b></b></span><b><b><span>Conclusion:</span></b><span></span></b> Ototoxicity, electrolyte imbalance, psychiatric disorders and gastrointestinal tract problems were the most frequently reported ADRs. </span></span></span><span><span><span>Healthcare providers,</span></span></span><span><span><span> government</span></span></span><span><span><span> and</span></span></span><span><span><span> donor agencies supporting the treatment should ensure that hearing aids and other forms of support are readily made available for the affected patients.</span></span></span>展开更多
Background:Anti-tuberculosis drug resistance is a major public health problem that threatens the progress made in tuberculosis care and control worldwide.Treatment success rates of multidrug-resistant tuberculosis(MDR...Background:Anti-tuberculosis drug resistance is a major public health problem that threatens the progress made in tuberculosis care and control worldwide.Treatment success rates of multidrug-resistant tuberculosis(MDR-TB)is a key issue that cannot be ignored.There is a paucity of evidence that assessed studies on the treatment of MDR-TB,which focus on the effectiveness of the directly observed treatment,short-course(DOTS)-Plus program.Therefore,it is crucial to assess and summarize the overall treatment outcomes for MDR-TB patients enrolled in the DOTS-Plus program in recent years.The purpose of this study was to thus assess and summarize the available evidence for MDR-TB treatment outcomes under DOTS-Plus.Methods:A systematic review and meta-analysis of published literature was conducted.Original studies were identified using the databases MEDLINE®/PubMed®,Hinari,and Google Scholar.Heterogeneity across studies was assessed using the Cochran’s Q test and I2 statistic.Pooled estimates of treatment outcomes were computed using the random effect model.Results:Based on the 14 observational studies included in the meta-analysis,it was determined that 5047 patients reported treatment outcomes.Of these,the pooled prevalence,63.5%(95%CI:58.4-68.5%)successfully completed full treatment(cured or treatment completed)with a pooled cure rate of 55.6%,whereas 12.6%(95%CI:9.0-16.2%)of the patients died,14.2%(95%CI:11.6-16.8%)defaulted from therapy,and 7.6%(95%CI:5.6-9.7%)failed therapy.Overall 35.4%(95%CI:30-40.8%)of patients had unsuccessful treatment outcomes.An unsatisfactorily high percentage 43%(95%CI:32-54%)of unsuccessful treatment outcomes was observed among patients who were enrolled in standardized treatment regimens.Conclusion:This study revealed that patients with MDR-TB exhibited a very low treatment success rate compared to the World Health Organization 2015 target of at least 75 to 90%.The high default rate observed by conducting this literature review could possibly explain the spread of the MDR-TB strain in various populations.A better treatment success rate was observed among patients in individualized treatment regimens than in standardized ones.Conducting further individual-based meta-analysis is recommended to identify potential factors for defaulting treatment using large-scale and multi-center studies.展开更多
基金supported by the Beijing Municipal Science&Technology Commission(Z191100006619077).
文摘Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.
基金Science and Technology Development Program of Linyi City(No:201113018)
文摘Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection mice.Methods:BALB/c mice were used as experimental animals,multidrug-resistant Mycobacterium tuberculosis infection models were built,randomly divided into model group,moxifloxacin group,thymopentin group and combined treatment group and given corresponding drug intervention,and then colony numbers in the spleen and lung,T lymphocyte subset contents and programmed death-1(PD-1) expression levels in peripheral blood were detected.Results:Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group:contents of CD3^+CD4^+T cells,Thl and Thl7 in peripheral blood of moxifloxacin group and thymopentin group were higher than dtose of model group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of model group;contents of CD3^+CD4^+T cells.Th 1 and Th 17 in peripheral blood of combined treatment group were higher than those of moxifloxacin group and thymopentin group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of moxifloxacin group and thymopentin group:PD-I expression levels on T lymphocyte,B lymphocyte and monocyte surface in peripheral blood of moxifloxacin group and thymopentin group were lower than those of model group,and PD-I expression levels on T lymphocyte.B lymphocyte and monocyte surface in peripheral blood of combined treatment group were lower than those of moxifloxacin group and thymopentin group.Conclusions:Immune formulation thymopentin can enhance the anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice,decrease bacterial load in lung and spleen,and enhance immune function.
文摘We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment;the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on antiretroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted.
文摘Background:Tuberculosis remains a major public-health problem in the world, despite several efforts to improve case identification and treatment. Particularly multidrug-resistant tuberculosis is becoming a major threat to tuberculosis control programs in Ethiopia which seriously threatens the control and prevention efforts and is associated with both high death rates and treatment costs. Methods: A case-control study was conducted to assess risk factors and characteristics of MDR-TB cases at ALERT Hospital, Addis Ababa, Ethiopia, where cases were 167 MDR-TB patients, while controls were newly diagnosed and bacteriologically confirmed pulmonary TB cases of similar number, who were matched by sex and age of 5-years interval. Results: The socio-demographic characteristics of the participants indicated that majority (53.3%) were males and 46.7% females;a little over half of cases (55.1%) were in the age group 26 - 45 years, whereas 46.7% of controls were in this age group. According to the multivariable logistic regression analysis, previous history of hospital admission was the only factor that was identified as predictor which increased risk to develop MDR-TB by almost twenty times (AOR = 19.5;95% CI: 9.17 - 41.62) and P-value of <0.05. All other studied factor such as being unemployed, family size, having member of household member with TB, and history of visiting hospital in past 12 months etc., didn’t show any statistically significant association. Conclusion: The study identified previous history of hospital admission as independent predictors for the occurrence of MDR-TB, while other studied variables didn’t show any strong association. The findings added to the pool of knowledge emphasizing the need for instituting strong infection control practice at health care facilities to prevent nosocomial transmission of MDR-TB.
文摘Multidrug resistant tuberculosis (MDR-TB) is an emerging challenge for TB control programs globally. Ethiopia ranks 7<sup>th</sup> among the world’s 22 high TB burden countries. According to report of WHO (2017), TB is one of the leading infectious causes of death in Ethiopia claiming the life of more than 30 thousand people annually. The surge of MDR-TB has been compounding the problem further. Facility-based MDR-TB researches have not been generated in equal pace with community-based ones. The aim of this study was to assess the prevalence of MDR-TB using clinical records of MDR-TB patients in Adama Hospital Medical College (AHMC) from 2014 to 2018. All clinical data of MDR-TB from 2014-2018 was collected from AHMC TB department. Socio-demographic and risk factor data were collected from patients using semi-structured questionnaire. Data were analyzed using Microsoft excel and SPSS version 20. Out of a total 2332 TB suspected cases admitted to AHMC from 2014 to 2018, 175 (7.5%) were confirmed MDR-TB cases or confirmed Rifampicin resistant cases. In particular, 97 (4.2%) presented presumptive MDR-TB alone and 78 (3.3%) showed confirmed Rifampicin resistance alone. Comparison among age groups showed the highest prevalence for 24 - 44 years with 1.8% and 1.5% confirmed MDR-TB and Rifampicin resistance. The overall prevalence of MDR-TB was moderate indicating for possible rise of the problem due to course of time. Further study combining both community and health facility based is recommended to highlight the need to make useful strategies for testing, surveillance and effective clinical management of MDR-TB cases.
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.
基金Major Science and Technology Projects in Hainan Province(ZDKJ2016008‑02)。
文摘Objective:To systematically review the influencing factors of the treatment outcome of multidrug-resistant pulmonary tuberculosis and provide reference for the prevention and treatment of multidrug-resistant pulmonary tuberculosis.Method:Case control studies on the factors influencing the treatment outcome of multidrug-resistant pulmonary tuberculosis in Chinese databases(CNKI,VIP,Wanfang,Sinomed)and English databases(Pubmed,Web of science,Medline,Embase,Scopus)were searched and collected by computer.The search period was from the establishment of the database to January 2023.After screening and quality evaluation,RevMan5.4 was used for meta-analysis.Result:Totally 18 articles were ultimately included,with a sample size of 7328 people.The results showed that retreatment,complications,adverse reactions,and gender were related to the treatment outcome of multidrug-resistant pulmonary tuberculosis.The OR values and 95%CI of each factor were 0.22(0.17-0.29),0.38(0.32-0.46),0.27(0.17-0.44),and 0.43(0.33-0.56),respectively.Conclusion:Complications,retreatment,adverse reactions,and male gender are effective risk factors for the treatment outcome of multidrug-resistant pulmonary tuberculosis.In clinical practice,more targeted measures are needed for different types of patients.Due to the limitations of the number of studies,the above conclusions require more research to support them.
文摘Background: For countries with limited resources such as the Democratic Republic of the Congo (DRC), the diagnosis of Multidrug-resistant tuberculosis (MDR-TB) is still insufficient. The MDR-TB identification is done primarily among at-risk groups. The knowledge of the true extent of the MDR-TB remains a major challenge. This study tries to determine the proportion of MDR-TB in each group of presumptive MDR-TB patients and to identify some associated factors. Methods: This is an analysis of the DRC surveillance between 2007 and 2016. The proportions were expressed in Percentage. The logistic regression permits to identify the associated factors with the RR-/MDR-TB with adjusted Odds-ratio and 95% CI. Significance defined as p ≤ 0.05. Results: Overall, 83% (5407/6512) of the MDR-TB presumptive cases had each a TB test. 86.5% (4676/5407) had each a culture and drug sensitive testing (DST) on solid medium, and 24.3% (1312/5407) had performed an Xpert MTB/RIF test. The proportion of those with at least one first-line drug resistance was 59.3% [95% CI 57.2 - 61.4] among which 50.1%, [95% CI 47.9 - 52.3] for the isoniazid, 45.6% [95% CI 43.4 - 47.8] for the rifampicin, 49.9% [95% CI 47.8 - 52.1] for ethambutol and 35.8% [95% CI 33.7 - 37.9] for streptomycin. The confirmation of MDR-TB was 42.8% [95% CI 38.4 - 47.8]. Combining both tests, the proportion of RR-/MDR-TB was 49.6% [95% CI 47.9 - 51.4] for all presumptives. This proportion was 60.0% for failures, 40.7% for relapses and 34.7% for defaulters. Associated factors with the diagnosis of MDR-TB were: aged less than 35 years;prior treatment failure;defaulters;the delay between the collection of sputum and the test completion. Conclusion: The proportion of RR-/MDR-TB among the presumptives has been higher than those estimated generally. The National tuberculosis programme (NTP) should improve patient follow-up to reduce TB treatment failures and defaulting. Moreover, while increasing the use of molecular tests, they should reduce sample delivery times when they use culture and DST concomitantly.
文摘Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. Because of the ototoxic effects of AGs, the World Health Organization (WHO) has recommended the introduction of the bedaquiline regimen. However, very few data are available regarding the susceptibility of bedaquiline to induce hearing loss, hence the present study set out to compare the AG-based regimen and the bedaquiline-based regimen in the occurrence of hearing loss in MDR-TB patients. Methods: This is a prospective multicenter cohort study that included 335 MDR-TB patients, performed in Kinshasa (DRC) during the period from January 2020 to January 2021. Sociodemographic, clinical, biological and audiometric data were analyzed using Stata 17. Repeated-measures analysis of variance was used to compare changes in the degree of hearing loss over time between the two groups of patients on AG and bedaquiline regimens. The double-difference method was estimated using regression with fixed-effects. A p value < 0.05 was considered the threshold for statistical significance. Results: The degree of hearing loss was similar between the two groups at the first month [AGs (28 dB) vs BDQ (30 dB);p = 0.298]. At six months, the mean degree of hearing loss was significantly greater in the aminoglycoside regimen group [AGs (60.5 dB) vs BDQ (44 dB);p < 0.001]. The double difference was significant, with a greater increase in hearing loss in the AGs group (diff-in-diff 18.3;p < 0.001). After adjustment for age and serum albumin, the group receiving the AG-based regimen had a 2-point greater worsening than those with bedaquiline at the sixth month (diff-in-diff 19.8;p Conclusion: Hearing loss is frequent with both treatment regimens, but more marked with the Aminoglycoside-based regimen. Thus, bedaquiline should also benefit for audiometric monitoring in future MDR-TB patients.
文摘Revised national tuberculosis control programme in India has limited co-hort-wise information about what happens to patients diagnosed with multidrug resistant TB (MDR-TB). We determined the pre-treatment loss to follow-up (non-initiation of treatment by programme within 6 months of diagnosis) and time from diagnosis to treatment initiation in Bhopal district, central India (2014). Pre-treatment loss to follow-up was 13% (0.95 CI: 7%, 23%), not significantly different from the national estimates (18%) and median time to initiate treatment was seven days, lower than that reported elsewhere in the country. Bhopal was performing well with reference to time to treatment initiation in programmatic settings.
文摘Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic sensorineural hearing loss. Research on risk factors is essential to enable high-risk individuals to benefit from preventive measures in settings with limited resources. Objective: This study aimed to assess the determinants of the hearing loss in patients with MDR-TB. Methods: This prospective multicenter cohort study included 337 patients with MDR-TB. It was performed in Kinshasa (Democratic Republic of the Congo) between January 2020 and January 2021. Sociodemographic, clinical, biological, therapeutic, and audiometric data were exported and analyzed using Stata 17 and MedCalc. The fixed-effect linear regression panel model was used to assess the degree of the hearing loss over time according to the following covariates: therapeutic regimen (aminoglycosides, bedaquiline, or alternate), stage of chronic kidney disease (CKD), age at inclusion, body mass index, serum albumin level, HIV status, alcohol intake, hypertension, and hemoglobin level. The Hausman test was used to select between fixed- and random-effect estimators. The threshold for statistical significance was set at p Result: A total of 236 patients (70%) received an aminoglycoside-based regimen, 61 (18%) received a bedaquiline-based regimen, and 40 (12%) received aminoglycosides relayed by bedaquiline. The frequency of the hearing loss increased from 62% to 96.3% within six months for all therapeutic regimens. The Hearing loss worsened, with moderate (72.4%) and profound (16%) deafness being predominant. An Exposure to the treatment for more than one month (β coeff: 27.695, Se: 0.793, p β coeff: 6.102, Se: 1.779, p β coeff: 5.610, Se: 1.682, p = 0.001), and an eGFR β coeff: 6.730, Se: 2.70, p = 0.013) were the independent risk factors associated with the hearing loss in patients with MDR-TB. Conclusions: The Hearing loss was more prevalent and worsened during the treatment of the patients with MDR-TB. An Exposure for more than one month, AG-based regimens, advanced age, hypoalbuminemia, and CKD have emerged as the main determinants of the worsening of the hearing loss.
文摘AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm<sup>3</sup>. In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.
文摘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.
基金Fundamental Research Program of Shanxi province(No.202103021223339,20210302124435)Shanxi Scholarship Council of China(No.2022-175)+1 种基金Fundamental Research Program of Shanxi Datong University(No.2019Q2,2019Q4)Doctoral Scientific Research Foundation of Shanxi Datong University(No.2018-B-13,2018-B-28)。
文摘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.
文摘Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis (MDR-TB) remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. Methods We used 12-locus mycobactedal interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects' medical records. Results All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR (DTM-PCR) identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit (MIRU) pattern (232225172531) and the same MIRU pattern (3677235). Strains from family-2 had the same MIRU pattern (2212261553323) and the same MIRU pattern (3685134). Strains from family-3 did not have the same MIRU pattern and they differed at only one locus (223326173533, 223325173533), and did not have the same VNTR pattern with two locus differed (3667233, 3677234). Conclusions Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a familv. Household tuberculosis transmission could be prevented with adequate treatment of source Patients.
文摘Background:Multidrug drug resistant Tuberculosis(MDR-TB)and extensively drug resistant Tuberculosis(XDR-TB)have emerged as significant public health threats worldwide.This systematic review and meta-analysis aimed to investigate the effects of community-based treatment to traditional hospitalization in improving treatment success rates among MDR-TB and XDR-TB patients in the 27 MDR-TB High burden countries(HBC).Methods:We searched PubMed,Cochrane,Lancet,Web of Science,International Journal of Tuberculosis and Lung Disease,and Centre for Reviews and Dissemination(CRD)for studies on community-based treatment and traditional hospitalization and MDR-TB and XDR-TB from the 27 MDR-TB HBC.Data on treatment success and failure rates were extracted from retrospective and prospective cohort studies,and a case control study.Sensitivity analysis,subgroup analyses,and meta-regression analysis were used to explore bias and potential sources of heterogeneity.Results:The final sample included 16 studies involving 3344 patients from nine countries;Bangladesh,China,Ethiopia,Kenya,India,South Africa,Philippines,Russia,and Uzbekistan.Based on a random-effects model,we observed a higher treatment success rate in community-based treatment(Point estimate=0.68,95%CI:0.59 to 0.76,p<0.01)compared to traditional hospitalization(Point estimate=0.57,95%CI:0.44 to 0.69,p<0.01).A lower treatment failure rate was observed in community-based treatment 7%(Point estimate=0.07,95%CI:0.03 to 0.10;p<0.01)compared to traditional hospitalization(Point estimate=0.188,95%CI:0.10 to 0.28;p<0.01).In the subgroup analysis,studies without HIV co-infected patients,directly observed therapy short course-plus(DOTS-Plus)implemented throughout therapy,treatment duration>18 months,and regimen with drugs>5 reported higher treatment success rate.In the meta-regression model,age of patients,adverse events,treatment duration,and lost to follow up explains some of the heterogeneity of treatment effects between studies.Conclusion:Community-based management improved treatment outcomes.A mix of interventions with DOTSPlus throughout therapy and treatment duration>18 months as well as strategies in place for lost to follow up and adverse events should be considered in MDR-TB and XDR-TB interventions,as they influenced positively,treatment success.
基金supported by the Beijing Medical Award Foundation [YJHYXKYJJ-104]
文摘Objective To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Methods Biapenem/clavulanate(BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis(Mtb) multidrug-resistant(MDR) isolates, extensively drug-resistant(XDR) isolates, and the H37 RV strain. BP/CL activity against the H37 Rv strain was assessed in liquid cultures, in macrophages, and in mice. Results BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units(CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment(isoniazid + rifampin + pyrazinamide) after 2 months of treatment. Conclusion BP/CL may provide a new option to clinically treat MDR tuberculosis.
文摘Background: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in Coastal region. This is a major challenge in tuberculosis control. Diagnosis is based on Ziel-Neelsen staining alone and patients are treated without information on sensitivity patterns. Aim: This study aimed to determine drug susceptibility patterns of Mycobacterium tuberculosis in Coastal Kenya. Study Design: Hospital and laboratory based cross-sectional study was carried between April 2015 and July 2016 at Coast General Referral hospital;Tudor, Port-Reitz, Likoni Sub-County hospitals;Mlaleo, Kongowea and Mikindani health centers. Methodology: Sputum samples from patients with bacteriological confirmed TB on microscopy were cultured on Lowenstein Jensen (LJ) media. Strains of MTB complex from Lowenstein Jensen (LJ) slopes were subjected to drug susceptibility testing (DST) to first-line drugs including isoniazid (H), rifampicin (R), streptomycin (S) and Ethambutol (E) using proportional method on the Mycobacterium Growth Indicator Tube (MGIT) conventional method. Participants were offered diagnostic testing and counselling for HIV testing. Results: Drug sensitivity test was performed for a total of 210 Mycobacterium tuberculosis isolates for the first line anti-TB drugs. About seventy eight percent and twenty nine percent of the strains from new patients and previously treated patients were fully sensitive to all the drugs tested respectively. Prevalence of any resistance to one drug was 102 (48.6%, 95% CI: 20.45 - 28.23). Any single drug resistance was most frequent in isoniazid 30 (16.0%), Ethambutol 20 (10.0%), Streptomycin 18 (18.3%) and Rifampicin 4 (2.1%) in newly diagnosed patients. Among previously treated patients any resistance to streptomycin, ethambutol, isoniaziad and rifampicin was 10 (58.8%), 9 (52.9%), 7 (41.2%) and 4 (23.5%) respectively. Prevalence of MDR-TB defined as resistant to at least both isoniazid and rifampicin was 10 (4.8%) among new and previously treated patients respectively. Conclusion: The current study reveals that the overall resistance to first line anti-TB drugs was high. Although the rate of MDR-TB was relatively low, this signifies that conditions favouring the spread of MDR-TB are on high rise. Therefore, it is essential to address the problems of development of drug re-sistant strains of TB by establishing good TB programmes (DOTS). Patients’ adherence to anti-TB drugs and introducing drug sensitivity testing (DST) services at County level hospitals will minimize occurrence of drug resistant.
文摘<b><span>Introduction:</span></b><span></span><b> </b><span>Multidrug</span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span>resistant tuberculosis (MDR-TB) is treated with second</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "=""><span>line antituberculosis drugs. These drugs are notorious for inflicting serious adverse drug reactions (ADRs), which many studies have shown causes a wide range of economic and health problems including death. <b></b></span><b><b><span>Aim:</span></b><span></span></b></span><b> </b><span>The study examined the prevalence of ADRs, associated risk factors, socio</span></span></span><span><span><span>-</span></span></span><span><span><span style="font-family:;" "=""><span>demographic association and outcomes among patients treated for MDR-TB at a comprehensive tuberculosis treatment center in Nigeria. <b></b></span><b><b><span>Method:</span></b><span></span></b> The study was conducted at the Government Chest Hospital, Jericho, Ibadan. We applied a </span></span></span><span><span><span>retrospective </span></span></span><span><span><span>assessment of patient treatment data and ADRs reports stored at the study site from March 2013 and February 2016. Subsequently, a prospective study of ADRs was conducted on patients admitted into the same hospital. Causality relationship between the drugs and the reported ADRs was determined with a special</span></span></span><span><span><span>l</span></span></span><span><span><span>y validated</span></span></span><span><span><span> tool. The outcomes assessed include recovery from the ADRs, death </span></span></span><span><span><span>and</span></span></span><span><span><span style="font-family:;" "=""><span> permanent deafness from the ADRs. Extracted data were analyzed using SPSS version 22.0. Risk Ratio was calculated for the influence of risk factors for adverse drug reactions. Logistic regression was performed to test for the strength of relationships between risk factors and incidence of ADRs among patients. <b></b></span><b><b><span>Result:</span></b><span></span></b> Almost all the participants in this study reported adverse drug reaction [99% (118/119)]. However, ototoxicity was the most prevalent ADR (35.3%), followed by electrolyte imbalance (12.6%)</span></span></span><span><span><span>,</span></span></span><span><span><span> gastrointestinal track (10.1%) and psychiatric disorders (10.1%). Being older than 35 years and HIV negative or having a healthy BMI were not significant risk factors for developing ADRs. </span></span></span><span><span><span>D</span></span></span><span><span><span style="font-family:;" "=""><span>uration of ADR above one month was significantly associated with the outcome of ADR. <b></b></span><b><b><span>Conclusion:</span></b><span></span></b> Ototoxicity, electrolyte imbalance, psychiatric disorders and gastrointestinal tract problems were the most frequently reported ADRs. </span></span></span><span><span><span>Healthcare providers,</span></span></span><span><span><span> government</span></span></span><span><span><span> and</span></span></span><span><span><span> donor agencies supporting the treatment should ensure that hearing aids and other forms of support are readily made available for the affected patients.</span></span></span>
基金The authors declare that they did not receive funding for this research from any source.
文摘Background:Anti-tuberculosis drug resistance is a major public health problem that threatens the progress made in tuberculosis care and control worldwide.Treatment success rates of multidrug-resistant tuberculosis(MDR-TB)is a key issue that cannot be ignored.There is a paucity of evidence that assessed studies on the treatment of MDR-TB,which focus on the effectiveness of the directly observed treatment,short-course(DOTS)-Plus program.Therefore,it is crucial to assess and summarize the overall treatment outcomes for MDR-TB patients enrolled in the DOTS-Plus program in recent years.The purpose of this study was to thus assess and summarize the available evidence for MDR-TB treatment outcomes under DOTS-Plus.Methods:A systematic review and meta-analysis of published literature was conducted.Original studies were identified using the databases MEDLINE®/PubMed®,Hinari,and Google Scholar.Heterogeneity across studies was assessed using the Cochran’s Q test and I2 statistic.Pooled estimates of treatment outcomes were computed using the random effect model.Results:Based on the 14 observational studies included in the meta-analysis,it was determined that 5047 patients reported treatment outcomes.Of these,the pooled prevalence,63.5%(95%CI:58.4-68.5%)successfully completed full treatment(cured or treatment completed)with a pooled cure rate of 55.6%,whereas 12.6%(95%CI:9.0-16.2%)of the patients died,14.2%(95%CI:11.6-16.8%)defaulted from therapy,and 7.6%(95%CI:5.6-9.7%)failed therapy.Overall 35.4%(95%CI:30-40.8%)of patients had unsuccessful treatment outcomes.An unsatisfactorily high percentage 43%(95%CI:32-54%)of unsuccessful treatment outcomes was observed among patients who were enrolled in standardized treatment regimens.Conclusion:This study revealed that patients with MDR-TB exhibited a very low treatment success rate compared to the World Health Organization 2015 target of at least 75 to 90%.The high default rate observed by conducting this literature review could possibly explain the spread of the MDR-TB strain in various populations.A better treatment success rate was observed among patients in individualized treatment regimens than in standardized ones.Conducting further individual-based meta-analysis is recommended to identify potential factors for defaulting treatment using large-scale and multi-center studies.