In this study*, it was aimed to observe, genotoxic effects of antituberculosis drugs and combinations on rats. Animals were treated with 31.5 mg/kg isoniazid (INH), 54 mg/kg rifampicin (RIF), 189 mg/kg pyrazinamide (PYR), 100 mg/kg etham-butol(ETA), INH+RIF+PYR (MIX1) and INH+RIF+PYR+ETA (MIX2) mixtures applied via gavage for 90 days. At the end of the study, blood, liver and kidney samples were taken and evaluated by Comet and Micronucleus techniques. Compared to control group, head intensity decreased, tail intensity and tail migration increased on experiment groups in blood samples. Head intensity of PYR and mixture groups decreased, tail intensity of PYR and mixture groups increased and tail migration of PYR, ETA and mixture groups increased in liver samples. Head intensity decreased and tail intensity increased of INH, RIF, ETA and MIX1 group; tail migration increased of MIX1 group in kidney samples. Compared to control group, micronucleus rate of ETA, RIF and MIX 2 groups increased in experiment groups. In conclusion antituberculosis drugs and their mixtures applied for 90 days causes to double strand break of DNA damage at different degrees in blood, kidney and liver cells in rats.
We performed a retrospective, observational study among XDR-tuberculosis patients to identify hospital-associated epidemiologic links. We used spoligotyping, IS6110-based restriction fragment-length polymorphism analysis, and sequencing of resistance-determining regions to identify clusters. Social network analysis was used to construct transmission networks among genotypically clustered patients.
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A 29-year-old man with painless ulcers on the lumbar and inguinal regions associated with purulent discharge of 1.5 years' duration presented to our outpatient clinic. Dermatological examination revealed palpable nodules, discharging sinuses and scars on the left lumbar, gluteal and inguinal regions. According to the clinical, histopathological, scintigraphy, and magnetic resonance imaging findings as well as mycobacteriological examinations, the patient was diagnosed with Pott's disease with scrofuloderma and psoas abscess. Herein, we present an interesting case of Pott's disease with scrofuloderma and psoas abscess mistreated as hidradenitis suppurativa for a long time.
Our data suggests that techniques (including Xpert MTB/RIF assay) relying on rifampicin susceptibility as an indicator for initiating first line therapy will not detect patients infected with MTB strains resistant to other first line drugs (including isoniazid). The roll out of these techniques must therefore be accompanied by strict monitoring ensuring early resistance detection to increase chances of improved patient outcomes.
Renal transplant recipients receiving immunosuppression show an increased risk for developing opportunistic infections, such as tuberculosis (TB). TB represents the major cause of morbidity and mortality in the world, mainly in underdeveloped countries. The aim of this study was to analyze the incidence of TB and its presentation among renal transplant recipients over 20 years.
The pooled analysis showed that the risk of developing drug-resistant TB to at least one anti-TB drug was about 3 times higher in individuals who had a previous history of anti-TB treatment than new TB cases. The risk of having MDR-TB in previously anti-TB treated TB cases was more than 5-fold higher than that of new TB cases. Resistance to Ethambutol and Rifampicin was more than fivefold higher among the previously treated with anti-TB drugs. However, HIV infection was not associated with drug-resistant TB.
In a multicenter study involving three reference centers for mycobacteria, the reliability of the Mycobacteria Growth Indicator Tube (MGIT) for rapid antimicrobial susceptibility testing (AST) of Mycobacterium tuberculosis was evaluated and compared to the radiometric method (BACTEC 460TB). Test cultures for which the results of the MGIT and BACTEC 460TB tests were discordant were checked by the conventional proportion method on solid medium. Four hundred forty-one isolates have been tested for susceptibility to isoniazid (INH), rifampin (RMP), ethambutol (EMB), and streptomycin (SM). Discrepant results were obtained for three isolates (0.7%) with INH (susceptible by MGIT, resistant by BACTEC 460TB), for four isolates (0.9%) with RMP (susceptible by MGIT, resistant by BACTEC 460TB), for six isolates (1.9%) with EMB (four susceptible by MGIT, resistant by BACTEC 460TB; two resistant by MGIT, susceptible by BACTEC 460TB), and for four isolates (0.9%) with SM (two susceptible by MGIT, resistant by BACTEC 460TB; two resistant by MGIT, susceptible by BACTEC 460TB). When cultures with discordant results were tested by the conventional proportion method, about half of the cultures yielded results similar to the BACTEC 460TB results, while the other half yielded results similar to the MGIT results. Turnaround times were 3 to 14 days (median, 8.8 days) for MGIT and 3 to 15 days (median, 7.8 days) for BACTEC 460TB. There was no statistically significant difference between the susceptibility testing results of the two methods (P > 0.05). These data demonstrate that the MGIT system is an accurate, nonradiometric alternative to the BACTEC 460TB method for rapid susceptibility testing of M. tuberculosis.
One hundred clinical isolates of M. tuberculosis were tested for four first line antitubercular drugs by nitrate reductase assay (NRA) and were compared with standard proportion method. The bacteria were inoculated on Lowenstein-Jensen (LJ) medium with primary antitubercular drugs and potassium nitrate was incorporated. After incubation for 7- 14 days, nitrate reduction indicating growth could be detected by colour change when reagents were added.
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A 92-year-old female ex-smoker with chronic obstructive pulmonary disease (COPD) GOLD III, was admitted because of communitarian pneumonia in November 2013. She had been using inhaled corticosteroids and bronchodilators and presented five exacerbations of COPD due to pneumonia in the same year, with hospitalizations in March and September. The patient underwent the routine protocol for exacerbated COPD, and bacilloscopy for tuberculosis (TB) was negative. On admission, she had intense dyspnea and a productive cough that improved by administration of levofloxacin. Tests with Ziehll-Neelsen staining in bronchopulmonary secretions resulted negative. Notwithstanding, during actual admission, the culture in Lowenstein-Jensen medium seeded in September was found positive for M. tuberculosis susceptible to isoniazid, rifampin, streptomycin, and ethambutol. Therefore, the patient underwent the standard regimen for tuberculosis. Except in September, when she used piperacillin-tazobactam, all previous exacerbations of COPD were treated with levofloxacin. This effective drug against M. tuberculosis can hinder its growth in culture. The use of levofloxacin in unsuspected TB may constitute an additional diagnostic challenge, and risk of late diagnosis is increased in patients with COPD in use of inhaled corticosteroids. Case studies may contribute to increase the suspicion index about TB associated with COPD.
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Our results suggest that the mortality of tuberculosis is high in patients in the early phase of maintenance dialysis and delay in the disease treatment of tuberculosis. Because of their generally poor state of nutrition, and depressed cellular immunity, the mortality is high in patients in the early stage of maintenance hemodialysis. Therefore, if the diagnosis is delayed, mortality is higher. Tuberculosis should be considered strongly and treated promptly if suspected.
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The Etest method for susceptibility testing of Mycobacterium tuberculosis was compared to the agar proportion method using four first-line agents and two fluoroquinolones. Catergorical agreement between the methods was 100% for rifampin, ethambutol, streptomycin, and ofloxacin and 98% for isoniazid. Results were obtained in 6 to 10 days by Etest. The Etest method is suitable for testing the agents evaluated against M. tuberculosis.
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In order to study certain epidemiological features of multidrug-resistant tuberculosis (MDR-TB) carriers and their influence on the control and treatment, a group of patients was evaluated over a four-year period, selected by: Mycobacterium tuberculosis isolation from sputum; resistance to Rifampin, Isoniazid and one more drug, or, failure of reserve regimen, all cases were from a tuberculosis reference unit in the City of S o Paulo. A total of 182 patients were reviewed, with a mean age of 35.7 +/- 6.8 years and 112 (61.5%) were male. These patients was classified according to therapeutic history, as: primary MDR-TB (with initial sensitivity test) 11 (6%); post primary MDR-TB (after irregular use previous treatment) 134 (74%), and indeterminate MDR-TB (failure after regular use of initial and reserve regimens) 37 (20%). Contagion was identified in 41/170 patients, acquired through domiciliary rather than institutional transmission. There were four familial outbreaks and none were institutional. The most frequent condition associated with these cases was abandonment of therapy (45%) followed by alcoholism (27%), sequential failure in the treatment regimens (23%), MDR contagion (15%), drug reaction (6%), HIV positive (4%) and diabetes (3%). There was resistance to Rifampin+Isoniazid in 100%, Streptomycin in 83% and Ethambutol in 47%. Conventional X-ray revealed cavities in all, though only 35 (19%) were unilateral. These cases are discussed and some suggestions presented.
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The activity of ciprofloxacin against 42 clinical isolates of mycobacteria was studied in vitro by the 1% standard proportion method on Lowenstein-Jensen medium. Ciprofloxacin was found active against all strains of Mycobacterium tuberculosis sensitive to streptomycin, isoniazid, ethambutol and rifampicin. The MIC of ciprofloxacin was 3.2 mg/l. This concentration of ciprofloxacin was sufficient to inhibit almost all strains showing intermediate sensitivity or resistance to one or more of the above agents. The same phenomenon was also observed with the atypical isolates.
Two tuberculosis (TB) reference hospitals in Maputo, Mozambique.
A pilot evaluation of DST proficiency was conducted in 2006 and scaled up in 2007. A panel consisting of 20 Mycobacterium tuberculosis isolates was used. Accuracy of 95% in detecting resistance to both isoniazid (INH) and rifampicin (RMP), and 90% to both ethambutol (EMB) and streptomycin (SM), was used to define a competent laboratory.
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To assist implementation of tuberculosis (TB) control measures, knowledge of the disease characteristics in a community is essential. This study in Kumasi, Ghana, correlates the clinical presentation, microbiology, molecular epidemiology and clinical outcome of thirty consecutively diagnosed patients with new smear-positive pulmonary TB. Several important factors that potentially promote disease transmission in the community were identified: patients had prolonged duration of productive cough prior to diagnosis (mean=4.1 months; SD=2.1); the disease was typically advanced at presentation and Ziehl-Neelson sputum smears indicated a high bacterial load (80% graded > AFB++); home accommodation was overcrowded with a mean of 3.3 other persons sleeping in the same room as the patients at night. IS6110 restriction fragment length polymorphism (RFLP) fingerprinting of 25 isolated (23 Mycobacterium tuberculosis and 2 Mycobacterium africanum) from epidemiologically unrelated cases identified 3 identical strains and 3 clusters containing 2, 4 and 8 isolates of > or =80% similarity, suggesting high rates of disease transmission. A high prevalence of primary resistance to isoniazid was found (6 out 26; 23%) but resistance to rifampicin, pyrazinamide, ethambutol, streptomycin and ciprofloxacin was not detected. Smear coversion at 2 months and final outcome of treatment with short courses chemotherapy were independent of isoniazid resistance, but the rate of treatment default was unacceptably high (37%). High rates of disease transmission, primary isoniazid resistance and treatment default all indicate poor TB control. The use of rifampicin-containing short-course chemotherapy in this community must be accompanied by adequate resources and infrastructure to ensure very stringent treatment supervision to improve case-holding and reduce the risk of multi-drug resistance.
A total of 1091 patients were enrolled during a 17-month period starting in June 2003, of whom 935 (85.7%) were new cases and 121 (11.1%) previously treated cases. Resistance to any of the four drugs was seen in 20.4% (95%CI 18.1-22.9) of new cases, in 38.8% (95%CI 27.8-51.1) of previously treated cases and in 22.1% (19.7-24.9) of both new and previously treated cases combined. The prevalence of multidrug resistance was respectively 3.8% (95%CI 2.6-5.5), 20.9% (95%CI 13.0-32.0) and 5.7% (95%CI 4.3-7.5). The prevalence of drug resistance among new cases was higher than the global average and it was widespread throughout the country.
Of the 118 patients suffering from chronic pulmonary tuberculosis, living within the district of the Tîrgu Mureş Tuberculosis Dispensary, 100 accepted a strictly surveyed treatment and of these 90 continued for at least 6 months. The present paper reports on the immediate radiologic and bacteriological results and the factors influencing them. The following conclusions were drawn: 1) A 2/7 Rifampicin/Etambutol strictly supervised treatment is the most efficient method for neutralizing chronic bacillary sources. 2) The age and origin of the patients, the duration and extent of the pulmonary process, duration of the treatment and associated diseases are the factors that furnish the prognosis of the expected results. 3) Apart from the very good results obtained the method cannot solve all chronic cases and the classical antiepidemic measures must be applied in continuation.
Clinical microbiology laboratories should provide reliable results on susceptibility testing of Mycobacterium tuberculosis to different agents.
The expected and observed attendance of patients during the intensive phase of anti-tuberculosis treatment was measured daily at two out-patient clinics in Dar es Salaam. During the observation period, treatment was changed from a regimen containing streptomycin to an all-oral regimen, and attendance proportions were compared for the three periods during which patients always, sometimes or never received streptomycin during the intensive phase of treatment.
The ethambutol/rifampicin combination with clarithromycin or moxifloxacin had significant bactericidal activity against M. xenopi. The nude mouse, being highly susceptible to M. xenopi, can be utilized for in vivo chemotherapy studies for this infection.
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The study was designed to evaluate the toxicity of anti-TB drugs in male Wistar rats and possible ameliorative effects of kolaviron (KV), a biflavonoid from Garcinia kola seeds.
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All the 78 controls were negative for culture and RT-PCR. Among the 301 sputum specimens from patients, 231 (76.8%) were RT-PCR positive and 70 (23.2%) were negative. There were 166 M. tuberculosis isolates, of which 11 (2.9%) were MDR-TB, 33 (8.7%) were polyresistant, 31 (8.2%) were monoresistant and 91 (30.2%) were sensitive to all five first line anti-tuberculous drugs by phenotypic drug susceptibility testing. Monoresistance was higher with Z [20 (20.8%)], followed by S [6 (3%)].