Model-based efficacy and toxicity comparisons of moxifloxacin for multi-drug-resistant tuberculosis

Background Moxifloxacin (MOX) is used as a first-choice drug to treat multi-drug-resistant tuberculosis (MDR-TB), however, evidence-based dosing optimization should be strengthened by integrative analysis. The primary goal of this study was to evaluate MOX efficacy and toxicity using integratvie model-based approaches in MDR-TB patients. Methods In total, 113 MDR-TB patients from five different clinical trials were analyzed for the development of a population pharmacokinetics (PK) model. A final population PK model was merged with a previously developed lung-lesion distribution and QT prolongation model. Monte Carlo simulation was used to calculate the probability target attainment (PTA) value based on concentration. An area under the concentration-time curve (AUC)-based target was identified as the minimum inhibitory concentration (MIC) of MOX isolated from MDR-TB patients. Results The presence of human immunodeficiency virus (HIV) increased clearance by 32.7% and decreased the AUC by 27.4%, compared with HIV-negative MDR-TB patients. A daily dose of 800 mg or a 400 mg twice daily dose of MOX is expected to be effective in MDR-TB patients with an MIC of ≤ 0.25 µg/mL, regardless of PK differences resulting from the presence of HIV. The effect of MOX in HIV-positive MDR-TB patients tended to be decreased dramatically from 0.5 µg/mL, in contrast to the findings in HIV-negative patients. A regimen of twice-daily doses of 400 mg should be considered safer than an 800 mg once-daily dosing regimen, because of the narrow fluctuation of concentrations. Conclusions Our results suggest that a 400 mg twice-daily dose of MOX is an optimal dosing regimen for MDR-TB patients because it provides superior efficacy and safety.

The Neglected Contribution of Streptomycin to the Tuberculosis Drug Resistance Problem

The airborne pathogen Mycobacterium tuberculosis is responsible for a present major public health problem worsened by the emergence of drug resistance. M. tuberculosis has acquired and developed streptomycin (STR) resistance mechanisms that have been maintained and transmitted in the population over the last decades. Indeed, STR resistant mutations are frequently identified across the main M. tuberculosis lineages that cause tuberculosis outbreaks worldwide. The spread of STR resistance is likely related to the low impact of the most frequent underlying mutations on the fitness of the bacteria. The withdrawal of STR from the first-line treatment of tuberculosis potentially lowered the importance of studying STR resistance. However, the prevalence of STR resistance remains very high, could be underestimated by current genotypic methods, and was found in outbreaks of multi-drug (MDR) and extensively drug (XDR) strains in different geographic regions. Therefore, the contribution of STR resistance to the problem of tuberculosis drug resistance should not be neglected. Here, we review the impact of STR resistance and detail well-known and novel candidate STR resistance mechanisms, genes, and mutations. In addition, we aim to provide insights into the possible role of STR resistance in the development of multi-drug resistant tuberculosis.

A simple HPLC-UV Method for Therapeutic Drug Monitoring of Linezolid in human Plasma in low-resourced settings

OBJECTIVE: A high-performance liquid chromatography method for the estimation of Linezolid in human plasma was developed and validated. METHODS: Samples (100µµL) were deproteinized with acetonitrile and analyzed using LiChrospher 100, RP18e column with PDA detection at 254 nm. The flow rate of the isocratic mobile phase comprising of 0.1% formic acid in 1000 ml of water and acetonitrile in the ratio of 60:40 (v/v) was set at 1.0 ml/min. RESULTS: The calibration curve ranged from 0.50 to 20.0 µg/ml and was linear. The recovery ranged from 96% to 101%. The accuracy ranged from 98 to 101% and intra- and inter-day relative standard deviation was <4.58%. The method reliably eliminated interfering materials from plasma and R2 was 0.9973. The method described was applied to the determination of plasma LZD concentration in multi-drug-resistant tuberculosis patients who are treated with a dose of 600 mg LZD once daily. CONCLUSIONS: The developed method is suitable for determination of plasma LZD in routine care and considered feasible in less-resourced settings

A TUBERCULOSE MULTIRRESISTENTE ASSOCIADA A ADMINISTRAÇÃO DE FÁRMACOS

Introdução: A tuberculose (TB), associada a infecção por micobactérias como os bacilos de Koch, não apresenta manifestações sintomáticas antes das primeiras 3 semanas de infecção. Após esse período sintomas como perda de peso acentuada, tosse com presença de inchaço nos gânglios e acometimento da região pulmonar começam a aparecer. Embora possua tratamento, administrado na comunidade pela equipe de saúde, a adesão dos pacientes tornou-se um problema de saúde pública, aumentando a mortalidade e morbidade dos pacientes se associado à administração irregular de fármacos para controle da infecção e a redução da condição imunológica do paciente por doenças oportunistas. Objetivos: Abordar as causas que podem levar ao desenvolvimento de tuberculose multirresistente associada a administração por fármacos. Material e métodos: Revisão da literatura de 2016 a 2021 com características descritivas, coletando produções por meio das bases de dados BVs e Scielo, com associação dos Descritores em Saúde (DECS) em inglês “Tuberculosis” e “Multi-drug resistant tuberculosis” e “Prevalence”. Resultados: Por meio das produções analisadas observou-se, o desenvolvimento em caráter resistente da tuberculose está relacionada a administração irregular de fármacos para combater infecções bacterianas, além das condições imunológicas do paciente, visto que indivíduos portadores do vírus da imunodeficiência adquirida (HIV/AIDS) possuem uma probabilidade maior de adquirir o bacilo resistente devido aos mecanismos de defesa imunológica debilitados por conta do tratamento da patologia. Ademais, pacientes com histórico hospitalar de tratamento de microbactérias ou de abandono do uso dos fármacos, são suscetíveis a desenvolverem a forma resistente da doença, devido ao contato prévio com os medicamentos e seu uso em dosagens incorretas. Esse mal-uso medicamentoso pode acarretar na seleção de cepas resistentes, deixando de ser eficaz ao tratamento inicial e contribuindo, assim, para a colonização e transmissão da sua forma resistente, reduzindo as chances de futuras intervenções. Conclusão: Dessa forma, percebe-se que a tuberculose multirresistente pode ser consequência do uso indevido de medicações que, associadas a fatores imunológicos, históricos patológicos, hospitalar e até mesmo fármacos bacteriostáticos, resultam no favorecimento da mutação do bacilo de Koch, selecionando cepas resistentes aos medicamentos utilizados no combate a TB.

Confronting and Coping with Multidrug-Resistant Tuberculosis: Life Experiences in Thailand

In this article, we aimed to understand the life experiences of Thai persons diagnosed with multi-drug-resistant tuberculosis (MDR-TB). A qualitative study using a face-to-face in-depth interview was conducted at a hospital in Thailand which has the highest prevalence of MDR-TB in the country between January and February 2019. Twenty persons living with MDR-TB in Thailand were purposively selected to represent a variety of experiences based on different gender, ages, and treatment phases. Qualitative data were transcribed and thematic analysis was applied to identify common themes and sub-themes. The results indicated that all participants faced emotional difficulties, such as fear of death, fear of stigmatization, confusion, and sadness when first knowing of their diagnosis. Family and social support were the main ways that the patients coped with difficult situations. Suicidal ideas were more prevalent among patients with poor family support. Screening for mental health problems should be routinely performed in MDR-TB patients. Proper health education should be provided to patients and families to reduce emotional difficulties and stigmatization.

Occupation and Treatment Outcome of Multi-drug resistant tuberculosis Patients

Background: Tuberculosis is a contagion from ancient times comprising around one 3rd of global population on the wedge of infection with Mycobacterium tuberculosis complex where under developed and developing countries is coping with high burden of the disease. Aim: To observe the most prevalent occupation and treatment outcome in both Genders of MDR TB patients. Methodology: Health Research Institute-National Institute of Health TB Research Centre in collaboration with Department of Pulmonology, King Edward Medical University/Mayo Hospital Lahore from january 2014 to December 2020. A pre-designed questionnaire was used to collect data from MDR Tb patients after verbal informed consent. Patients were followed to see the final outcome on completion of anti-tubercle treatment. Data was entered and analyzed by using SPSS. Results: Out of total 450 MDR TB patients analyzed in this study a higher proportion of 54.9% were males and 45.1% were females with an overall mean age of patients as 39.64±17.52 years. Most of 159(35.4%) patients had no skills and were labors whereas most of 145 (28.2%) females were house wives. Almost 71% of the patients successfully completed the treatment including 45% cured on the basis of availability of final smear and culture reports.. Conclusion: A high mortality rate of MDR TB patients was observed while most of the TB patients in this study belong to labor class while most of the women were housewives. Keywords: Tuberculosis, MDR TB, Occupation, Treatment outcome, loss to follow up.

The efficacy of bedaquiline versus kanamycin in multi-drug resistant tuberculosis: A systematic scoping review

Background: Drug-resistant tuberculosis (DR-TB) has become a serious cause of concern both on a global scale and in South Africa. It is associated with a lower successful treatment rate, thus creating a hurdle in achieving good treatment outcomes for patients.Aim: The aim of this study was to compare the efficacy of the drug kanamycin, an injectable aminoglycoside, to bedaquiline, a newer oral drug used to treat DR-TB.Methods: PubMed and Google Scholar, both of which are online databases, were extensively searched using the necessary keywords so that studies that were relevant to the scoping review were retrieved. A data-charting list was developed to extract the needed data for this scoping review.Results: The main findings of the scoping review showed that bedaquiline was highly efficacious in the treatment of DR-TB, and that it was a valuable addition in the treatment of DR-TB. The findings of the study also showed that kanamycin does not have good efficacy against DR-TB. and its use extends the treatment of DR˗TB.Conclusion: It stands to reason that bedaquiline replaces kanamycin in the DR-TB drug regimen as it was shown to be more efficacious and patients experienced better treatment outcomes in a shorter period of time. There were also fewer adverse effects associated with bedaquiline as compared to kanamycin.Contribution: Bedaquiline-based DR-TB therapy is more efficacious than aminoglycoside-based regimens which include kanamycin.

Drug Resistant Tuberculosis in the Northern Region of Zambia: A Retrospective Study

BackgroundZambia like many countries in sub-Saharan Africa is affected with drug resistant tuberculosis. However, the drug resistant tuberculosis situation over the years has not been described in various regions of the country. Consequently, this study aims to determine the drug resistant tuberculosis burden in northern regions of Zambia over a four-year period based on data generated from a Regional Tuberculosis Reference Laboratory.MethodTwo hundred and thirty two (232) Tuberculosis Drug Susceptibility Testing results over a four-year period (2016-2019) were reviewed. Data was collected from tuberculosis registers and patient request forms and entered into a pre-tested standardized checklist and later entered in Excel Computer software. Double blinded checking was done by two independent data clerks to minimize duplication of cases. Cleaned data was then imported in R programme for analysis. Bivariant and descriptive statistics were performed and reported.ResultsOf 232 Drug Susceptibility Testing results, 90.9% were drug resistant TB while 9% were drug susceptible. Fifty three percent (53%) of these were multi-drug resistant Tuberculosis and 32% were confirmed as Rifampicin Mono-resistance. Only 1.7% of the Multi-drug resistant Tuberculosis patients were Pre-extensively drug-resistant Tuberculosis. Copperbelt province had the largest proportion (46.0%) of multi-drug resistant tuberculosis patients followed by Luapula (8.1%) and North-Western (4.7%) provinces. In new and previously treated patients, the proportion of Multi-drug resistant tuberculosis was 71.8% and 28.7% respectively. History of previous anti-tuberculosis treatment and treatment failure were associated with multi-drug resistance TB.Conclusion and RecommendationThis study has shown a small increase in the proportions of drug resistant tuberculosis cases over the four years under review with high rates being recorded on the Copperbelt Province. Previous treatment to first line TB treatment and treatment failure were associated with development of Multi-drug resistance. We therefore recommend strengthened routine laboratory surveillance and improved case management of multi-drug resistant tuberculosis patients in the region.