MDR/XDR TB

Tuberculosis (TB) is one of the world’s deadliest diseases. TB has never spread as today do. Population size growth and other factors, particularly HIV, contribute to TB incidence. Multidrug-resistant tuberculosis (MDR-TB) defined as Mycobacterium tuberculosis
resistant to at least isoniazid (INH) and rifampicin (RMP) (the two most powerful anti-TB drugs), is a rapidly emerging disease characterized by difficulties in treatment (longer, more expensive and with toxic drugs) and high rates of morbidity and mortality.

According to the data from MOJ the prevalence of hepatitis infection is very high among the prisoners and growths up to 60%. The importance of the research has been determined by the lack of knowledge about the role of co-infection and other risk factors in MDR-TB treatment, particularly in prison, where the prevalence rate of HIV and hepatitis C&B co-infection was higher than among the general population due to some social, environmental features of detainers life However, the information about impact of co-infection alone and in cooperation with other risk factors on MDR-TB treatment outcome is limited.

Objective: The aim of operational research is to analyze the poor results of treatment of MDR-TB and define risk factors.

Results: Out of 268 patients completed treatment with second line medicine 18.3% (49) had poor outcome (treatment failure or dead), while 81.7% (219) of patients had success.

ABSTRACT

Background: There is a global epidemic of Tuberculosis with over 1.9 million deaths Results: One hundred and fifty MDR-TB MDR TB be- came a major concern in Sub1
patients were enrolled in the study of which Saharan Africa
67% were male and 33% were female. About 92% were retreatment cases, 32% had clinical anaemia, and 13% were HIV positive. 47%.% of patients had normal BMI during admission, globally per annum. Over the past decade, which increased to 59. % by 4 months of
genomic studies have been conducted in an treatment 92% had successful outcome while
attempt to elucidate the functionality of the 8% were unsuccessful. Study showed that there
genome of TB. Nigeria is one of the 14 countries is a significant association between the baseline
with a significant MDR-TB burden, there is an PCV, HIV status, and history of hypertension
increased focus on MDR TB disease control and and treatment outcome of the MDR-TB patient
prevention at 4 months. FGDs of 16 male and 8 female
Methods: The study was a descriptive MDR TB patients suggested Oral medication
retrospective study of 150 patients who were enhances better adherence and a better
diagnosed using the GeneXpert and referred to treatment outcome by majority of the MDR TB
the Osun state DR-TB treatment centre at Iwo. patients.
Data were collected from the patients' case files Conclusion Public Health Policy can be
which include information like age, sex, weight changed to reflect the new Oral medications for
on admission, weight on discharge, height, MDR TB patients to enhance good adherence
results of baseline investigations like PCV, HIV, on treatment, this will encourage good cure rate
co-morbidities like diabetes mellitus, and prevent retreatment as much as possible.
hypertension were also collated. Data were Keywords: Policy Implication, Oral
analyzed using IBM (SPSS) version 25 and a Drugs,drug resistant tuberculosis, treatment
test of significance were taken at P<0.05. Focus centre, Outcome.
Group Discussion for patients on admission on
possible change from injectable to oral INTRODUCTION
medication for MDR TB patients. Altas.ti a MDR TB is tuberculosis disease caused by
qualitative research tool was used for coding Mycobacterium. Tuberculosis that is resistant
and analyzing transcripts after back translation to the two most effective and important TB
and content analysis drugs, Isoniazid (INH) and Rifampin (RIF).

Al día de hoy se sabe que en la génesis y mantenimiento efectivo de una célula tumoral participan el mantenimiento de señales de proliferación celular, la evasión de los mecanismos supresores, resistencia a la apoptosis, replicación ilimitada, inducción de la angiogénesis, invasión y metástasis. Recientemente se han postulado también las alteraciones al equilibrio energético celular y la expresión de genes de resistencia a múltiples fármacos. La metformina, un medicamento prescrito durante más de 50 años, es en la actualidad el patrón de referencia en el tratamiento de pacientes diabéticos no insulinodependientes debido a
que tiene mecanismos de acción capaces de regular los mecanismos de obtención de energía. A partir de la administración tan difundida de este fármaco en todo el mundo, surgieron diversas cohortes que apuntaban a que metformina era un factor protector contra el cáncer. Esta teoría
se ha trasladado de manera exitosa a experimentos in vitro e in vivo, confirmándose las propiedades antitumorales, al parecer, mediadas por la inhibición de la vía LBK1/AMPK/mTOR y del IGF-1R. Por esta razón, en apenas menos de una década es posible encontrar ensayos clínicos de la adición de metformina a los esquemas de quimioterapia contra casi todos los tipos de cáncer. Sin duda alguna, se seguirán generando y consolidando los conocimientos de los efectos de metformina descritos e incluso de otros más inesperados, como los efectos sinérgicos que parece tener con los antibióticos en el tratamiento de la tuberculosis multirresistente.

Background Among the resistant isolates of MTB, multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) have been the areas of growing concern. The genomic analysis showed that the respective genomic pool of the XDR-MTB proteome contains more than 30% of the hypothetical proteins for which no functions have been annotated yet. This class of proteins presumably have their own importance to complete genome and proteome information. The bioinformatics advancements have helped to annotate those hypothetical proteins by using various computational tools and have potential to classify them functionally. Objective The objective of this study was to propose a new and unique drug target against the deadly Mycobacterium tuberculosis using Bioinformatics approaches to characterize the hypothetical proteins. Results We stepwise reduced the hypothetical proteins (total number: 1256) out of the complete proteome to only 26 essential hypothetical proteins. Out of those 26 proteins, the protein WP_003401246.1 was computationally characterized as the druggable target. Conclusion The study proposed a hypothetical protein from complete proteome of the XDR-MTB as a new drug target against which new drug candidates can be proposed. Hence, the study opens up the new avenues in the areas of drug discovery against deadly M. tuberculosis.

Background: The global pandemic of tuberculosis has left everlasting scars on people’s lives. Drug-resistant tuberculosis is becoming an increasingly serious hazard to public health. With over 240,000 fatalities due to drug-resistant tuberculosis (DR-TB) worldwide, and Nigeria is one of the 14 nations with a significant multi-drug resistant TB burden, increased focus on dis-ease control is needed. Methods: The study was a retrospective cohort study. A total of 149 patients diagnosed using the gene Xpert machine and referred to the DR-TB treatment centers in University College Hospital and Government Chest Hospital were recruited. Data were collected from the patients’ case files and analyzed using Statistical Package for Social Sciences (SPSS) version 25. Results: One hundred and forty-nine MDR-TB patients were enrolled in the study, of which 12.75% were new cases while 130 (87.2%) were on retreatment. The prevalence of MDR TB mortality was 4%. However, 30.9% had normal PCV at basel...

Adherence to antiretroviral therapy (ART) and second-line antituberculosis medications is essential to achieve successful outcomes among individuals co-infected with HIV and multi or extensively drug-resistant TB (M/XDR-TB). In 2012–2013, we designed a qualitative study to explore barriers to adherence in KwaZulu-Natal, South Africa. We conducted six focus groups comprising 23 adults receiving treatment for either MDR-TB (n = 2) or XDR-TB (n = 21); 17 were on concurrent ART. Participants expressed a preference for ART over M/XDR-TB treatment as a result of greater tolerability, lower pill burden and a commitment to ART. Treatment outcomes and the social morbidity associated with M/XDR-TB, characterised by public notification, stigma and social isolation, were perceived to be worse than with HIV. Poor communication, low patient involvement and provider supervision of treatment exacerbated participants’ negative experiences with TB care. To improve adherence, it is critical that new r...

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p&lt;0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6–9) versus 5 (4–6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49–156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and w...

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/ clavulanate to treat multidrug-and extensively drug-resistant tuberculosis (MDR-and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR-and XDR-TB cases. Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6–9) versus 5 (4–6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49–156) days. No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment). The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR-and XDR-TB cases. @ERSpublications Meropenem/clavulanate is effective and safe to treat MDR-and XDR-TB in comparison with controls http://ow.ly/XG75j

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p&lt;0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6–9) versus 5 (4–6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49–156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and w...

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Adherence to antiretroviral therapy (ART) and second-line antituberculosis medications is essential to achieve successful outcomes among individuals co-infected with HIV and multi or extensively drug-resistant TB (M/XDR-TB). In 2012–2013, we designed a qualitative study to explore barriers to adherence in KwaZulu-Natal, South Africa. We conducted six focus groups comprising 23 adults receiving treatment for either MDR-TB (n = 2) or XDR-TB (n = 21); 17 were on concurrent ART. Participants expressed a preference for ART over M/XDR-TB treatment as a result of greater tolerability, lower pill burden and a commitment to ART. Treatment outcomes and the social morbidity associated with M/XDR-TB, characterised by public notification, stigma and social isolation, were perceived to be worse than with HIV. Poor communication, low patient involvement and provider supervision of treatment exacerbated participants’ negative experiences with TB care. To improve adherence, it is critical that new regimens for drug-resistant TB be developed with better efficacy, lower pill burden and fewer adverse effects. For the first time, such improved regimens are on the horizon. In parallel and equally important is the implementation of a cohesive approach that promotes patient involvement, empowerment and treatment literacy for HIV and for TB.