The clinical manife stations and CT scans of 14 cases of intracerebral tuberculomas were reviewed. 9 cases were associated with tuberculous meningitis. The images of the tuberculomas on CT scans appeared to be disc-like, ring-like or irregular in shape. The irregular mass consisted of multiple discs or rings coalescing to produce such irregular contours. On the plain scans, fewer of the tuberculomas showed images of low density or isodenseimages they became clear images of high density on the enhanced scans. Of the 5 cases not associated with tuberculous meningitis, 3 had epilepsies. The experience obtained in recent years indicated that the majority of tuberculomas could decrease in size or completely reabsorbed with adequate antituberculous medications. For the treatment of intracerebral tuberulomas it was recommended to use regular doses of Isoniazid, Rifampin, Ethambutol and other antituberculous drugs in combination for one to one and half years. Surgery should be performed when necessary.
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We searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2013, Issue 1); MEDLINE; EMBASE; LILACS; Science Citation Index; Databases of Russian Publications; and metaRegister of Controlled Trials up to 6 March 2013.
Tuberculosis is one of the major public health problems worldwide. Modern antituberculous treatment can cure most patients; cure rates > 95% are achieved with standard short-course chemotherapy regimens containing isoniazid, rifampicin, pyrazinamide, and ethambutol among patients with drug-susceptible strains of tuberculosis; however, a small proportion do not respond to treatment or develop serious adverse events. Pharmacogenomic studies of drugs used in the treatment of tuberculosis could help us understand intersubject variations in treatment response. In this review, we compiled pharmacogenomic data on antituberculous drugs that were available from different settings that would give a better insight into the role of pharmacogenomics in the treatment of tuberculosis, thereby enhancing the efficacy and limiting the toxicity of existing antituberculosis medications.
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Overall, 49.6% of participants were infected with a Mycobacterium tuberculosis strain resistant to at least one prescribed anti-tuberculosis medication. PROMDR-TB and MDR-TB were prevalent in 17.2% and 13.1% of participants, respectively. Logistic regression modeling indicated that good residence (OR 3.1, 95%CI 1.4-6.9), treatment default (OR 4.4, 95%CI 2.1-9.3) and psychological disorder (OR 3.3, 95%CI 1.0-10.9) were associated with PROMDR-TB. Both good residence (OR 2.6, 95%CI 1.1-6.0) and treatment default (OR 5.3, 95%CI 2.4-11.6) were associated with MDR-TB. History of incarceration was not found to be significant.
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232 patients were found, from whom NTM were isolated from the respiratory tract in 91% of cases. Patients were mostly white men, with an average age of 60 years and pre-existing pulmonary disease. Fifty-three of 212 patients (25%) with pulmonary isolates met the ATS diagnostic criteria for pulmonary NTM disease; this percentage differed by species. Most patients were treated with rifampicin, ethambutol and clarithromycin. Treatment outcome for pulmonary NTM disease was suboptimal but differed by species: overall, improvement was seen in 67% of treated patients, but in only 50% of those with pulmonary M avium disease. Lymphadenitis was the most common extrapulmonary disease type.
A total of 100 isolates were tested for isoniazid, rifampin, streptomycin and ethambutol susceptibility using an indirect-proportion method as well as the E-test method.
We describe the first case, to our knowledge, of Mycobacterium brisbanense species nova with the type strain W6743T (=ATCC 49938T=DSM 44680T) isolated from the lungs of a man with a 6-month history of productive cough and intermittent fever presenting with acute hypoglycemia. A CT scan of the thorax revealed multiple small nodules and consolidation over both lungs with cavitation. Sputum culture repeatedly grew M brisbanense species nova, a novel species never before isolated in Malaysia. The case met the American Thoracic Society criteria for the diagnosis of nontuberculous mycobacterial infection. There was dramatic clinical and radiologic response to treatment with an empirical combination of rifampicin, ethambutol, and levofloxacin and subsequently clarithromycin and levofloxacin once sensitivity was known. This report is the first, to our knowledge, of the pathogen isolated in a patient with chronic cavitary lung infection since it was first identified from an antral sinus in Brisbane, Queensland, Australia, and the first time it is isolated from a human subject in Malaysia.
The HIV-TB co-infected children had a mean age of 105.9 months (standard deviation 43.1); there were 10 girls (41.7%). The maximum plasma concentration (Cmax), time taken to achieve Cmax, area under curve from 0-4 h and 2 h concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) were not affected by the HIV status of the children. Ethambutol (EMB) concentrations were lower in HIV-TB co-infected children. Inadequate 2 h concentrations of INH, RMP and EMB were found in the majority of the children in both groups. PZA concentrations were adequate in almost all children. Younger age and lower dose were associated with lower 2 h concentrations of INH and RMP.
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There are limited data on TB among prison inmates in Bangladesh. The aim of the study was to determine the prevalence of pulmonary tuberculosis (TB), its drug resistance and risk factors in Dhaka Central Jail, the largest prison in Bangladesh.
Report on 6,200 control examinations of patients treated with Ethambutol. Subjective troubles of vision do not influence continuation of therapy. In 8 patients (0,5%) symptoms of neuritis nervioptici accompanied with visus deterioration required to stop therapy (case reports on these 8 patients). Ophthalmologic control examinations are recommended before beginning therapy, during continuous therapy in hospital every eight week, and in case of ambulatory intermitting therapy every third to fourth month.
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Frequency of resistance-conferring mutations vary among isoniazid- and ethambutol-resistant Mycobacterium tuberculosis isolates obtained from patients of various ethnic groups. This study was aimed to determine the occurrence of specific rpoB mutations in rifampicin-resistant M. tuberculosis isolates from tuberculosis patients of various ethnic groups in Kuwait.
Taiwanese data on disease burden of TB and anti-microbial resistance of MTB identified from Annual Reports of Centre for Disease Control, Department of Health, Taiwan and from peer-reviewed publications from MEDLINE (1995-2004).
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The authors describe a rare case of rifampicin-induced skin toxicity and the related diagnostic and therapeutic difficulties.
To describe the prevalence and epidemiological-clinical characteristics of tuberculosis (TB) resistance to first-line drugs in Italian human immunodeficiency virus (HIV)-infected subjects.
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To study the laboratory diagnosis of tuberculosis (TB), and relate the findings to its epidemiology in Central Saudi Arabia.
A total of 254 Mycobacterium tuberculosis strains were used in the study. Among them, there were 183 ethambutol (EMB)-resistant strains, 13 multidrug resistant ones, but EMB-sensitive, and 39 strains sensitive to rifampicin (RIF), isoniazid (INZ), and EMB. All the strains were analyzed for genetic changes in three loci: embB306, rpoB, and katG/inhA promoter, which were associated with the formation of resistance to EMB, RIF, and INZ, respectively. The Mycobacterium tuberculosis strains were obtained from pulmonary tuberculosis patients living in the Central Region of the Russian Federation. Resistance to RIF, INZ, and EMB was revealed by the absolute concentration test. The inhibitory concentration (IC) of EMB was determined for all the strains. Genetic changes in the above loci were estimated by mini-sequencing, followed by mass-spectrometry recording MALDI-TOF products. The relative low frequency of embB306 mutations was observed among the EMB-resistant strains (about 41.5%). Mutations in codon 306 were detected only in strains with EMB IC > or = 2 mg/L. A statistical significant association was found between the frequency of embB306 mutations and the multidrug resistant phenotype. A combination of these mutations with the traditional genetic markers of multidrug resistance may be used for the more effective detection of multidrug-resistant strains.
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The potential of genetic testing to rapidly diagnose drug resistance has lead to the development of new diagnostic assays. However, prior to implementation in a given setting, the association of specific mutations with specific drug resistance phenotypes should be evaluated. The purpose of this study was to evaluate molecular markers in predicting drug resistance in the Central Region of Cameroon.
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The authors examined the efficacy of various chemotherapeutic regimes in the management of patients with tuberculosis of the prostate. The data of bacteriostatic secretion activity of the prostate showed that the most effective regimes were as follows: 1) isoniazid and ethambutol followed by galvanization of the prostatic region, then rifampicin suppository containing dimexid; 2) isoniazid and rifampicin suppository containing dimexid; oral ethambutol. Proper curative measures depending on the clinicomorphological types of the tuberculous prostate and their duration are also given. Using the proposed regimes in 68 patients provided 80.7-96.6% positive responses. The authors advise to carry out seasonal courses of chemotherapy using mainly the method of rectal administration of anti-tuberculous agents, dimexid and tissue electrophoresis.
A total of 95 drug-resistant M. tuberculosis isolates collected from three different centers were included in this study. Susceptibility testing of the isolates to four major antituberculous drugs was performed using proportion method on Löwenstein-Jensen medium and BACTEC 460-TB system. All clinical isolates were typed by using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) methods. Seventy-three of the 95 (76.8%) drug resistant M. tuberculosis isolates were isoniazid-resistant, 45 (47.4%) were rifampicin-resistant, 32 (33.7%) were streptomycin-resistant and 31 (32.6%) were ethambutol-resistant. The proportion of multidrug-resistant isolates (MDR) was 42.1%. By using spoligotyping, 35 distinct patterns were observed; 75 clinical isolates were grouped in 15 clusters (clustering rate of 79%) and 20 isolates displayed unique patterns. Five of these 20 unique patterns corresponded to orphan patterns in the SITVIT2 database, while 4 shared types containing 8 isolates were newly created. The most prevalent M. tuberculosis lineages were: Haarlem (23/95, 24.2%), ill-defined T superfamily (22/95, 23.2%), the Turkey family (19/95, 20%; previously designated as LAM7-TUR), Beijing (6/95, 6.3%), and Latin-America & Mediterranean (LAM, 5/95 or 5.3%), followed by Manu (3/95, 3.2%) and S (1/95, 1%) lineages. Four of the six Beijing family isolates (66.7%) were MDR. A combination of IS6110-RFLP and spoligotyping reduced the clustering rate from 79% to 11.5% among the drug resistant isolates.
Our findings support the hypothesis that drug-resistant disease among the Tomsk city population is not directly linked to history of incarceration, nor is it an extension of drug resistance in prisons. Rather, drug resistance in the civil sector reflects problems specific to the sector itself.
To evaluate the clinical presentation, biochemical (ascites and serum) and laparoscopic findings, and to assess the efficacy of triple antituberculous therapy without rifampicin for 6 months in patients with tuberculous peritonitis.
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Opportunist mycobacterial infections localised to the chest may be treated with combinations of standard antimycobacterial drugs. The combination of rifampicin and ethambutol seems to be particularly effective, both in vivo and in vitro. In vitro sensitivity testing with single drugs may have a role in the future when the levels of in vitro resistance compatible with the clinical response to treatment are eventually established. Sensitivity testing against drugs in combination may prove useful for modifying treatment regimens in those patients who either fail to respond to initial chemotherapy or relapse. Further evidence on this will, it is hoped, emerge from the prospective studies currently in progress.
Rifampin is frequently used in the treatment of mycobacterial infections. Intermittent or discontinuous therapy with rifampin has been associated with systemic symptoms referred to as the "flu syndrome" and, less frequently, acute hemolysis and acute renal failure. We report the case of a 73-year-old woman who experienced acute hemolysis and renal failure while being treated with rifampin and ethambutol for a respiratory infection caused by Mycobacterium fortuitum and M. avium-intracellulare. This patient had interrupted her therapy for periods of one week or more due to a rash and flu-like symptoms, which she ascribed to her medications. A review of the literature indicated that these adverse effects of rifampin appear to be immunologically mediated and that the symptoms of the flu syndrome may be due to mild intravascular hemolysis. Intermittent therapy with rifampin should be avoided and noncompliant patients should be given alternative treatment when possible.
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For the purpose to compare the effectiveness of SM and EB as a third drug in the standard regimens and to know whether the addition of SM twice weekly to INH and RFP could be acceptable for the treatment of pulmonary tuberculosis, the efficacy, adverse effects and results of long-term follow-up of the groups consisting of 105 patients treated with SM twice weekly for 6 months in addition to INH and RFP for 9 months (S2 group) and 107 patients treated with EB for 6 months in addition to INH and RFP for 9 months (E group) were observed. The speed of negative conversion of sputum and that of X-ray findings improvement were slightly faster in S2 group than E group but the difference was statistically not significant. The incidence of adverse effects such as elevation of serum transaminase values, gastrointestinal troubles, drug allergy and others was not similar in two groups. The relapse was observed in 2 cases of S2 group and 5 cases of E group. We concluded that SM twice weekly to INH and RFP is similarly effective as EB in combination with INH and RFP, and the this regimen could be used as standard regimen for pulmonary tuberculosis.
N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N and C terminal domains catalyzes uridyltransferase and acetyltransferase activities, respectively. Final product of GlmU catalyzed reaction, uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc), acts as sugar donor providing GlcNAc residues in the synthesis of peptidoglycan and a disaccharide linker (D-N-GlcNAc-1-rhamnose), the key structural components of Mycobacterium tuberculosis (M. tuberculosis) cell wall. In the present study, we have searched new inhibitors against acetyltransferase activity of M. tuberculosis GlmU. A subset of 1607 synthetic compounds, selected through dual approach i.e., in-silico and whole cell screen against 20,000 compounds from ChemBridge library, was further screened using an in-vitro high throughput bioassay to identify inhibitors of acetyltransferase domain of M. tuberculosis GlmU. Four compounds were found to inhibit GlmU enzyme specific to acetyltransferase activity, with IC50 values ranging from 9 to 70 μM. Two compounds (6624116, 5655606) also exhibited whole cell activity against drug susceptible as well as drug resistant M. tuberculosis. These two compounds also exhibited increased anti-TB activity when tested in combination with rifampicin, isoniazid and ethambutol, however 5655606 was cytotoxic to eukaryotic cell line. These results demonstrate that identified chemical scaffolds can be used as inhibitors of M. tuberculosis cell wall enzyme after optimizations for future anti-TB drug development program.
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Mycobacterium avium and M. intracellulare were isolated from the sputum of patients infected with atypical mycobacteria using 1% Ogawa medium and identified by the DNA probe test. Then the MICs of various kinds of drugs against these mycobacterial species were determined on Dubos agar medium, and the drug susceptibilities were also determined on 1% Ogawa medium in parallel. The drugs tested were new macrolides, such as clarithromycin (CAM) and roxithromycin (RXM), new quinolones, such as ofloxacin (OFLX) and ciprofloxacin (CPFX), and antituberculous drugs, such as isoniazid (INH), rifampicin (PFP), streptomycin (SM), and ethambutol (EB). The MICs of the drugs tested, especially those of CAM, OFLX, and RFP, when determined on Dubos agar medium, were generally lower against M. intracellulare than against M. avium. The susceptibilities of the mycobacterial isolates tested to RFP and SM determined on Dubos agar medium were markedly different from those determined on 1% Ogawa medium. Such discrepancies may be accounted for by absorption of these drugs to the egg medium and instability of RFP in the egg medium. Overall, our results indicate that the new macrolides and new quinolones are effective against atypical mycobacteria.