Factors associated with sputum conversion time among patients with drug-resistant tuberculosis in Kenya

Background: Drug-resistant tuberculosis (DR-TB) is a form of antimicrobial resistance that is difficult and costly to treat. It is caused by TB bacteria that are resistant to at least one of the first-line existing TB medications, resulting in fewer treatment options and increasing mortality rates. Treatment for this form of TB, known as DR-TB, requires a minimum of 18-24 months of treatment with drugs that are less effective, more toxic, and more expensive than those needed for drug-susceptible TB. Methods: This was a retrospective review of secondary data for patients diagnosed with DR-TB in Kenya from 2014 to 2019. Each patient had a two-year follow-up period to monitor sputum conversion time and the associated factors. The enrolled patients comprised all patients diagnosed with DR-TB within the 47 counties in Kenya and enrolled at any drug-resistant registered treatment center. Results: A total of 2674 patients were enrolled for review to establish factors associated with conversion and we only found out that the type of resistance a patient enrolled on gender, intensive phase regiment, modification of intensive phase, and waiting time before treatment initiation were the only significant factors that would influence when a patient would convert from being sputum positive to negative. Conclusions: Patients with resistant TB require correct diagnosis and timely start of medication with good follow-up to avoid being lost to follow-up or failing on the medication started. Additionally, healthcare workers need continuous training to gain more knowledge in case of detection for patients coming to hospitals.

Impact of adverse drug reaction on quality of life in drug resistant tuberculosis

Background: India has largest population of drug resistant tuberculosis, the treatment of which is long and full of adverse drug reactions. Despite the ongoing research in clinical and pharmacological aspects, quality of life in drug-resistant tuberculosis remains less explored. This study aims to study the quality of life in drug-resistant tuberculosis patients before and after treatment of the adverse drug reactions. Methods: This hospital based cross-sectional study done in the at tertiary care center in Surat, from January 2019 to February 2020, enrolling patients above 18 years, with multi-drug/ extensively drug resistant tuberculosis, who suffered > 1 adverse drug reaction after commencing treatment. SF-36 was administered at start of treatment and after treatment of first adverse drug reaction, and scores compared. Paired Student T Test was used for comparison of pre - post scores. p -value < 0.05 is considered statistically significant. Results: Among the 120 patients studied, majority (87.5%) were had pulmonary tuberculosis. 92.5% and 7.2% were multi-drug resistant and extensively drug resistant respectively. A significant improvement in QOL scores was seen in all 3 domains post treatment of adverse drug reaction- physical domain: After vs. Before: 55.2�8 vs. 25.2�2; (p-value < 0.0001), mental domain: After vs. Before: 66.8�7 vs. 39.4�1; (p-value < 0.0001) and social domain After vs. Before: 65.4�5 vs. 39.7�0; p-value < 0.0001). Conclusions: Drug-resistant tuberculosis along with its associated adverse drug reactions greatly impacts the quality of life in all domains. However, prevention and effective treatment of such adverse effects, especially in systematic protocolised manner can do wonders in improving the life of these patients.

Obstacles in combating multidrug resistant tuberculosis in pediatric patients: a scope review / Obstáculos no combate à tuberculose multidroga resistente em pacientes pediátricos: uma revisão de escopo

Abstract Objectives: to identify the scientific evidence on excessively resistant and multidrug resistant tuberculosis in pediatric patients. Methods: this is a scope review of the literature, with a guiding question: "What is the scientific evidence on multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis in pediatric patients?". The research used the descriptors: "extensively drug-resistant tuberculosis" OR "multidrug-resistant tuberculosis" AND "pediatrics". The research was carried out in a double-blind manner in the following databases of the Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier and International Clinical Trials Registry Platform, with a temporal cut-off from 2011 to 2021, sending a final synthesized sample of 18 articles, which evaluated the methodological content through the level of evidence. Results: the results show the lack of research with a high level of evidence related to MDR-TB in children, the lack of adequate dosage of second-line drugs for the pediatric population and the importance of drug sensitivity testing for the cases of treatment Conclusions: it was identified that the obstacles to MDR-TB treatment were concentrated in the lack of detailed protocols, safe drug dosages with a low side effect, and mainly in the social health determinants and disease process involving MDR-TB.

Resumo Objetivos: identificar as evidências científicas sobre tuberculose excessivamente resistente e multidroga resistente em pacientes pediátricos. Métodos: trata-se de uma revisão de escopo da literatura, tendo como questão norteadora: "Quais as evidências científicas sobre tuberculose multidroga-resistente (TB-MDR) e tuberculose extensivamente resistente em pacientes pediátricos?" A pesquisa usou os descritores: "tuberculose extensivamente resistente a medicamentos" OR "tuberculose resistente a múltiplos medicamentos" AND "pediatria". A pesquisa foi realizada de modo duplo-cego nas bases de dados Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier e International Clinical Trials Registry Platform, com um corte temporal de 2011 a 2021, sendo a amostra final sintetizada de 18 artigos, nos quais avaliou-se o conteúdo metodológico por meio do nível de evidência. Resultados: os resultados mostraram a escassez de pesquisas de alto nível de evidência relacionadas à TB-MDR em crianças, ausência de posologia adequada das drogas de segunda linha para o público pediátrico e a importância do teste de sensibilidade a drogas para o tratamento dos casos. Conclusões: identificou-se que os obstáculos do tratamento TB-MDR se concentraram na ausência de protocolos detalhados, de dosagens medicamentosas seguras e com menor efeito colateral, e, principalmente, nos determinantes sociais do processo saúde e doença que envolvem a TB-MDR.

The performance of Xpert MTB/RIF and MTBDRplus within a Programmatic setting at TB Laboratory in Rio de Janeiro, Brazil

ABSTRACT Background: Few studies in routine settings have confirmed the high accuracy of the Xpert MTB/RIF assay for detecting rifampicin resistance (RR) and the first-line probe assay (FL-LPA) for detecting both RR and isoniazid resistance (INHR). Methods: The performance of Xpert MTB/RIF and MTBDRplus VER 2.0 LPA was evaluated in 180 Mycobacterium tuberculosis samples collected from January 2018 to December 2019 in Rio de Janeiro, Brazil. The results were compared with those from BACTEC MGIT 960 culture and drug susceptibility testing (DST). Whole-genome sequencing was performed on the samples with discordant results. Results: The Xpert MTB/RIF assay showed a sensitivity (Se) of 93.3% and a specificity (Sp) of 97.6%, detecting RR. The performance of FL-LPA to identify RIF and INH resistance was, respectively, (Se) 100% and 83.3% and (Sp) 98.8% and 100%. Among 18 clinical isolates with INHR detected by FL-LPA, mutations in the katG gene were observed in 100% of samples, of which only two (11.1%) had mutations in both katG and inhA genes. Overall, the discordant results were identified in 9 (5%) samples. Among the four Xpert RIF-resistant and DST-sensitive, two harbored mutations in rpoB Leu430Pro. Among the four FL-LPA-sensitive and DST-resistant, one had a mutation in inhA 17G>T. FL-LPA showed high accuracy in detecting RR and INHR. Conclusions: The MTBDRplus test demonstrated excellent performance in detecting RR, and INHR in clinical isolates under routine conditions at a reference laboratory in Rio de Janeiro, Brazil. Incorporating both tests can improve drug-resistant tuberculosis treatment outcomes and monitor the INHR incidence.

Discordancia entre pruebas de susceptibilidad genotípicas y fenotípicas para tuberculosis en Cali, Colombia: un reto en la práctica clínica / Discordance between genotypic and phenotypic susceptibility tests for tuberculosis in Cali, Colombia: a challenge in the clinical practice

INTRODUCCIÓN: La detección de patrones de resistencia de Mycobacterium tuberculosis se basa en pruebas de susceptibilidad fenotípicas y genotípicas. Los resultados discordantes entre ellas son un desafío clínico para el manejo de pacientes con tuberculosis resistente a fármacos. OBJETIVO: Evaluar la concordancia entre pruebas fenotípicas y moleculares en pacientes con tuberculosis resistente a fármacos atendidos en una institución de Cali, Colombia. MATERIALES Y MÉTODOS: Se realizó un estudio transversal en el que se obtuvo el perfil de sensibilidad fenotípico de cultivos de micobacterias y la susceptibilidad genotípica con las pruebas moleculares Xpert-MTB/ RIF® o Genotype-MDRTBplus ®. Se evaluó el porcentaje de resistencia y porcentaje de acuerdo entre los resultados de las pruebas fenotípicas y genotípicas. Se estimó un coeficiente de kappa de Cohen (κ) para cada tipo de resistencia según la prueba utilizada. RESULTADOS: Se incluyeron 30 casos con resultados de pruebas genotípicas y fenotípicas. Las pruebas fenotípicas detectaron resistencia a fármacos de primera línea en 29/30 casos, mientras que las moleculares detectaron la resistencia en todos los casos evaluados. El porcentaje de resistencia a rifampicina detectado entre la prueba fenotípica y Genotype-MDRTBplus ® &e 61,5% (acuerdo global 41,1%, κ = 0,40, p = 0,96), mientras que el porcentaje de resistencia detectado con Xpert-MTB/RIF® fue 100% (acuerdo global 81,82%, κ: 0,00, p < 0,001) para este mismo medicamento. El porcentaje de resistencia a isoniacida detectado entre la prueba fenotípica y Genotype-MDRTBplus ® fue 94,4% (acuerdo global 89,47%, κ: -0,055 p = 0,59). CONCLUSIONES: La discordancia entre los resultados de las pruebas genotípicas y fenotípicas es posible, por lo que es importante usar e interpretar ambos tipos de pruebas de manera complementaria en el diagnóstico de la resistencia a fármacos de primera línea en la infección por M. tuberculosis.

BACKGROUND: The detection of Mycobacterium tuberculosis resistance patterns is based on phenotypic and genotypic susceptibility tests. The discordant results between them are a clinical challenge for the management of patients with drug-resistant tuberculosis. Aim: To evaluate the concordance between phenotypic and molecular tests in patients with drug-resistant tuberculosis treated in an institution in Cali, Colombia. METHODS: A cross-sectional study was conducted. A phenotypic sensitivity profile was obtained from mycobacterial cultures. The genotypic susceptibility was obtained with Xpert-MTB/ RIF® or Genotype-MDRTBplus ®. The percentage of resistance and percentage of agreement between the results of the phenotypic and genotypic tests were evaluated. A Cohen's kappa coefficient (κ) was estimated for each type of resistance according to the test used. RESULTS: A total of 30 cases with both genotypic and phenotypic testing were included. The phenotypic tests detected resistance to first-line drugs in 29/30 cases, while the molecular tests detected resistance in all the cases evaluated. The percentage of resistance detected between Genotype-MDRTBplus® and the phenotypic test for rifampicin was 61.5% (overall agreement 41.1%, κ = 0.40, p = 0.96), while the percentage of resistance detected with XpertMTB/RIF® was 100% (overall agreement 81.82%, κ: 0.00, p < 0.001) for this same drug. Resistance to isoniazid detected by both types of tests was 94.4% (overall agreement 89.47%, κ: -0.055 p = 0.59). CONCLUSIONS: Discordance between the results of genotypic and phenotypic tests is possible, so it is important to use and interpret both types of tests in a complementary way in the diagnosis of resistance to first-line drugs in M. tuberculosis infection.

Factores asociados a tuberculosis pre extensamente resistente en pacientes del Hospital Nacional Dos de Mayo, Lima, Perú / Factors associated with pre-extensively drug-resistant tuberculosis in patients at Dos de Mayo National Hospital, Lima - Perú

INTRODUCCIÓN: La resistencia a fármacos antituberculosos está influenciada por las características personales y las condiciones de salud de países en vías de desarrollo. OBJETIVO: Determinar los factores asociados a TB-pre extensamente resistente (TB-PRE XDR) en pacientes del Hospital Nacional Dos de Mayo (HNDM) entre 2017 y 2019. PACIENTES Y MÉTODO: Se desarrolló un estudio caso control no pareado, definiendo como caso al paciente con TB- PRE XDR y como control al paciente con TB-S. Se recolectaron variables epidemiológicas, clínicas y radiológicas. RESULTADOS: Se analizaron 51 casos y 102 controles. El análisis bivariado determinó como factores con p 51 años (OR: 0,17, IC95%: 0,05-0,51), uso de drogas (OR:2,5, IC95%: 1,1-5,4), antecedente de TB (OR: 20, IC95%: 8,4-47), reclusión previa (OR: 8, IC95%: 2,7-23,8), infección por VIH (OR: 0,2, IC95%: 0,08-1) y uso previo de fármacos antituberculosos (OR: 21, IC95%: 8,8-50). El análisis de regresión logística identificó como factores asociados a TB-PRE XDR al contacto de TB, antecedente de TB, tiempo de enfermedad y uso previo de fármacos antituberculosos. CONCLUSIÓN: Las medidas para limitar el desarrollo de TB-PRE XDR en pacientes con TB-S deben incidir sobre el antecedente de TB, contacto con TB, tiempo de enfermedad y uso previo de anti-TB no controlados; sin embargo, existen resultados no concluyentes sobre el hábito nocivo y la comorbilidad, siendo necesario más estudios para determinar su influencia como factores asociados identificables.

BACKGROUND: Resistance to anti-TB drugs is influenced by personal characteristics and health conditions in developing countries. AIM: To determine the factors associated with pre-extensively drug-resistant tuberculosis (PRE XDR-TB) at Hospital Nacional Dos de Mayo (HNDM) in patients between the 2017 and 2019. METHODS: An unpaired case control study was developed; defining as case PRE XDR-TB patient and as control S-TB patient. Epidemiological, clinical and radiological variables were collected. RESULTS: We analyzed 51 cases and 102 controls. The bivariate analysis showed as factors with p 51 years (OR: 0.17, 95% CI: 0.05-0.51), drug use (OR: 2.5, 95% CI: 1.1-5.4), previous history of TB (OR: 20, 95% CI: 8.4-47), previous confinement (OR: 8, 95% CI: 2.7-23.8), HIV infection (OR: 0.2, 95% CI: 0.08-1) and previous use of antiTB drugs (OR: 21, 95% CI: 8.8-50). The logistic regression analysis identified as associated factors with PRE XDR-TB the previous contact with TB, a history of TB, length of illness and previous use of tuberculosis antibiotics. CONCLUSION: The measures to limit the development of TB-PRE XDR in patients with TB-S must include the previous history of TB, TB contact, length of illness and previous use of uncontrolled antibiotics against TB; however, there are inconclusive results about the harmful habits and comorbidity, requiring more studies to determine their influence as identifiable associated factors.

Factores de riesgo asociados a la farmacorresistencia y al tratamiento no exitoso de la tuberculosis en Chile 2014-2018 / Risk factors and predictors of drug resistance in tuberculosis: A comprehensive analysis of cases in Chile (2014-2018)

OBJETIVOS: Determinar los factores de riesgos asociados a la farmacorresistencia y al tratamiento no exitoso de tuberculosis en Chile durante el 20142018. METODOLOGÍA: Estudio transversal observacional analítico que incluye los pacientes notificados con tuberculosis (TB) que ingresaron a tratamiento durante el 2014-2018 en Chile, contenidos en el registro nacional TB. Se determinaron variables demográficas, clínicas y grupos de riesgos asociados a la farmacorresistencia y al tratamiento no exitoso en pacientes con TB mediante regresión logística. RESULTADOS: Entre los años 2014-2018 se notificaron 13.1761 pacientes con TB en Chile, de los cuales 3,4% (n = 445) son farmacorresistentes. El 43,1% de estos son TB resistente a rifampicina (TB-RR), multidrogorresistente (TB-MDR) y extensamente resistente (TB-XDR). Los factores de riesgo que generaron mayor probabilidad de presentar farmacorresistencia fueron la recaída (OR: 4,27; IC 95% 2,94; 6,20), extranjero (OR: 3,97; IC 95% 2,86; 5,52), TB pulmonar (OR: 2,92; IC 95% 1,71; 4,99) y VIH (OR: 1,97; IC 95% 1,33; 2,90). Frente a la probabilidad de generar un tratamiento no exitoso, las variables que presentaron mayor probabilidad fueron situación de calle (OR: 3,33; IC 95% 2,45; 4,52), drogadicción (OR: 1,91; IC 95% 1,52; 2,41), extranjero (OR: 1,51; IC: 95% 1,25; 1,83), farmacorresistencia (OR: 2,81; IC 95% 1,87; 4,20), VIH (OR: 3,24; IC: 95% 2,61; 4,02), no pertenecer a un pueblo indígena (OR: 1,43; IC: 95% 1,00; 2,06) alcoholismo (OR: 1,25; IC 95% 1,01; 1,54), TB pulmonar (OR: 1,43; IC 95% 1,20; 1,70) y sexo masculino (OR: 1,44; IC 95% 1,25; 1,65). CONCLUSIONES: Los factores de riesgo identificados como la recaída y la coinfección con VIH como predictores de farmacorresistencia destaca la complejidad del manejo de la enfermedad. Asimismo, la presencia de situaciones de calle, drogadicción y alcoholismo resalta la necesidad de enfoques específicos y personalizados para abordar la tuberculosis en distintos grupos poblacionales. Estos resultados subrayan la importancia de abordar estos factores de riesgo en la gestión y tratamiento de la tuberculosis en Chile, sugiriendo la necesidad de estrategias específicas y personalizadas.

OBJECTIVE: Determine the risk factors associated with drug resistance and unsuccessful treatment of tuberculosis in Chile between 2014 and 2018. METHODOLOGY: Analytical observational cross-sectional study including patients diagnosed with Tuberculosis (TB) who entered treatment during 2014-2018, contained in the national TB records. Demographic, clinical variables, and risk groups associated with drug resistance and unsuccessful treatment in TB patients were determined using logistic regression. RESULTS: Between 2014 and 2018, 13,1761 TB patients were reported in Chile, of whom 3.4% (n = 445) were drug-resistant. From this, 43.1% are rifampicin-resistant TB (RR-TB), multidrug-resistant (MDR-TB), and extensively drug-resistant (XDR-TB). The risk factors that generated the highest probability of drug resistance were relapse (OR: 4.27; CI95% 2.94; 6.20), foreigner (OR: 3.97; CI95% 2.86; 5.52), pulmonary TB (OR: 2.92; CI95% 1.71; 4.99) and HIV (OR: 1.97; CI: 95% 1.33; 2.90). Regarding the probability of unsuccessful treatment against TB, the highest probability were street situation (OR: 3.33; CI: 95% 2.45; 4.52), drug addiction (OR: 1.91; CI 95% 1.52; 2.41), foreigner (OR: 1.51; CI 95% 1.25; 1.83), drug resistance (OR: 2.81; CI 95% 1.87; 4.20), HIV (OR: 3.24; CI: 95% 2.61; 4.02), not belonging to an indigenous people (OR: 1.43; CI 95% 1.00; 2.06) alcoholism (OR: 1.25; CI 95% 1.01; 1.54), pulmonary TB (OR: 1.43; CI 95% 1.20; 1.70) and male sex (OR: 1.44; CI 95% 1.25; 1.65). CONCLUSIONS: The risk factors identified as relapse and coinfection with HIV as predictors of drug resistance highlight the complexity of disease management. Likewise, the presence of street situations, drug addiction, and alcoholism highlights the need for specific approaches to address tuberculosis in different population groups, suggesting the need for personalized strategies.

Comparación de regímenes de linezolid, en adición a bedaquilina y pretomanida, para el manejo de tuberculosis farmacorresistente (estudio ZeNix): Lectura crítica / Comparison of linezolid regimens, in addition to bedaquiline and pretomanid, for the management of drug-resistant tuberculosis (the ZeNix study): Critical reading

RESUMEN Presentación: En el presente artículo exponemos nuestra valoración crítica de un ensayo clínico aleatorizado publicado en la revista New England Journal of Medicine el año 2022. Conclusiones del estudio: El estudio compara cuatro regímenes de linezolid (en adición a bedaquilina y pretomanid) para el manejo de tuberculosis farmacorresistente. Finalmente, se demuestra que el régimen de 600 mg de linezolid durante 26 semanas tuvo menos frecuencia de falla terapéutica y eventos adversos (en comparación con darlo por menos semanas o a más dosis). Comentario crítico: El artículo es relevante porque aún no es clara la dosis adecuada de linezolid y la duración del tratamiento con este agente para minimizar los efectos adversos y mantener la eficacia contra la tuberculosis altamente resistente. A pesar de algunas limitaciones como el bajo número de participantes, la alta pérdida al seguimiento, y el no realizar comparaciones estadísticas entre grupos; los resultados son relativamente confiables para la toma de decisiones.

ABSTRACT Presentation: In this article we present our critical appraisal of a randomized clinical trial published in the New England Journal of Medicine in 2022. Study conclusions: The study compares four linezolid regimens (in addition to bedaquiline and pretomanid) for the management of drug-resistant tuberculosis. Finally, it shows that the regimen of 600 mg of linezolid for 26 weeks had less frequency of therapeutic failure and adverse events (compared to giving it for fewer weeks or at higher doses). Critical comment: The article is relevant because the appropriate dose of linezolid and duration of treatment with this agent to minimize adverse effects and maintain efficacy against highly resistant tuberculosis is still unclear. Despite some limitations such as low number of participants, high loss to follow-up, and no statistical comparisons between groups, the results are relatively reliable for decision making.

Study of side effect profile of bedaquiline containing regimen among patients with extensively drug-resistant tuberculosis at a nodal drug-resistant center

Background: Extensively drug-resistant tuberculosis (XDR TB) is a type of tuberculosis (TB) characterized by resistance to isoniazid and rifampicin, along with resistance to one of the fluoroquinolones and at least one of the second line injectable drugs. Bedaquiline is a diarylquinoline antimycobacterial agent approved for the treatment of adults with pulmonary multidrug-resistant TB (MDR-TB) and XDR-TB by the food and drug administration. Aim and Objective: The aim of this study was to study the side effect profile of bedaquiline containing regimen among XDR TB patients. Materials and Methods: This study was conducted at outpatient and wards of nodal drug-resistant TB Center, Department of Pulmonary Medicine, SVRRGGH, Tirupati, for a period of 1 year. Forty patients of more than 18 years age and diagnosed with XDR TB were included in the study. Bedaquiline was started and daily monitoring was done with ECG and all organ function tests were repeated every 15 days. Results: All 40 cases were retreatment cases; no new XDR TB case was reported in study period. Most common age group of presentation in our study was 46 to 55 years (32.5%). Gastrointestinal adverse drug reactions were found to be more common (37.5%), cardiovascular QTc changes were observed in 10% of patients, 5% of patients had neurological reactions (Headache), 2.5% of patients had peripheral neuropathy, and 2.5% of patients had arthralgia. Conclusions: Bedaquiline containing regimen is very effective for the treatment of XDR TB cases. The study shows that compliance with this regimen is very good. Bedaquiline has minimal adverse reactions and even these are easily manageable. Bedaquiline has good safety profile and patients have improved quality of life.

Development of a novel luminescence reporter mycobacteriophage for rapid drug susceptibility testing of Mycobacterium tuberculosis / 中华微生物学和免疫学杂志

Objective:To construct a new reporter mycobacteriophage, ΦFN, based on a nanoluciferase (Nluc) reporter system, and to analyze its ability to detect drug resistance in Mycobacterium tuberculosis ( Mtb). Methods:A Nluc reporter system controlled by P furAma promoter was constructed and integrated into Mycobacterium smegmatis ( Msm) genome to assess its reporting ability in mycobacteria. Then the P furAma- nluc reporter system was integrated into TM4 mycobacteriophage genome to construct a new phage termed ΦFN. A rapid procedure for detecting drug resistance in mycobacteria using ΦFN was established by adjusting conditions such as drug exposure time and time of infection. The susceptibility of 52 clinical isolates of Mtb with known drug resistance to three first-line anti-tuberculosis drugs were tested in 96-well plates. Results:The recombinant Msm mc 2155 expressing P furAma- nluc repoerter system could generate luminescence signal at a low limit of 100 colony-forming unit (CFU), which was lower than the previously reported nluc system controlled by Pleft promoter. The detection limit of ΦFN for mycobacteria reached 100 CFU within 24 h by luminescent microplate reader. After 48 h of antibiotic exposure and 24 h of phage incubation, no luminescence signal could be detected when susceptible strains were below 10 5 CFU, which could effectively distinguish susceptible strains and rapidly detect drug resistance. The drug susceptibility of 52 clinical isolates of Mtb to rifampin, isoniazid and streptomycin was tested using ΦFN, and the accuracy was 51/52, 48/52 and 49/52, respectively, by using the conventional drug susceptibility test, Lwenstein-Jensen culture medium assay, as reference. Conclusions:The new recombinant luminescent reporter phage, ΦFN, showed high accuracy in detecting the drug susceptibility of Mtb to rifampicin, isoniazid and streptomycin and it only took three days. It is expected to be a new simple assay for the rapid detection of drug susceptibility of Mtb.

Risk factors of drug resistance in diabetes mellitus complicated by pulmonary tuberculosis / 中国基层医药

Objective:To investigate the risk factors of diabetes mellitus complicated by pulmonary tuberculosis.Methods:The clinical data of 83 patients with diabetes mellitus complicated by pulmonary tuberculosis who received treatment in Taiyuan Fourth People's Hospital from March 2020 to March 2022 were collected. These patients were divided into sensitive group ( n = 45) and resistant group ( n = 38 ) according to the results of drug sensitivity test. Univariate and multivariate non-conditional logistic regression was performed to analyze the influential factors of drug resistance. Results:Univariate logistic regression results revealed that there were significant differences in blood CD4 +T lymphocyte count ( χ2 = 11.73, P = 0.001) and diabetic complications ( χ2 = 4.94, P = 0.026). Multivariate non-conditional logistic regression analysis was performed taking whether blood CD4 +T lymphocyte count was lower than the average level and whether patients with diabetes mellitus had complications as independent variables, and taking whether drug resistance was a dependent variable. The results showed that the OR (95% CI) value of the decreased blood CD4 +T lymphocyte count was 4.909 (1.926-12.514). It is a risk factor for drug resistance of diabetes mellitus complicated by pulmonary tuberculosis. Conclusion:The decrease of blood CD4 +T lymphocyte count is a risk factor of drug resistance in diabetes mellitus complicated by pulmonary tuberculosis, and it should be intervened early in the clinic.

Efficacy and safety evaluation of the regimen containing Bedaquiline in elderly patients with drug-resistant pulmonary tuberculosis / 中华老年医学杂志

Objective:To evaluate the efficacy and adverse reactions of the regimen containing Bedaquiline in elderly patients with multi-drug resistant tuberculosis.Methods:From March 2019 to June 2022, patients with multi-drug resistant pulmonary tuberculosis admitted to Anhui Chest Hospital were randomly divided into two groups: the observation group was given a treatment containing Bedaquiline, and the control group was given a treatment without Bedaquiline.Patients were also divided into elderly patients(age ≥60 years old)and non-elderly patients(age <60 years old)according to age.Sputum culture conversion, lesion absorption and adverse reactions were compared between the observation group and the control group in general, elderly and non-elderly patients, respectively.Results:A total of 170 cases were collected, including 79 in the observation group and 91 in the control group.Sputum culture conversion: The sputum culture conversion rates of observation groups in general, non-elderly and elderly patients were better than that of control groups at the 3rd month after treatment(the general, 96.2% vs.75.8%, χ2=14.001, P<0.001; the non-elderly, 94.9% vs.82.1%, χ2=4.675, P=0.031; the elderly, 100.0% vs. 65.7%, χ2=8.771, P=0.003), and at the 6th month, the rates of overall observation group was better than that of control group(98.7% vs.92.3%, χ2=3.895, P=0.048); the rates of non-elderly and elderly observation group and control group were all greater than 90%, with no statistical significance( P>0.05). Lesion absorption: Overall and non-elderly observation groups were better than control group in lesion absorption at the 3rd month(the general, 84.8% vs.68.1%, χ2=12.962, P=0.002; the non-elderly, 88.1% vs.71.4%, χ2=9.832, P=0.007; and the 6th month(the general, 88.6% vs.76.9%, χ2=14.888, P=0.001; the non-elderly, 89.8% vs.82.1%, χ2=8.618, P=0.013). The focal absorptivity of senile observation group at the end of March and June were 75.0% and 85.0%, respectively, both better than control group, but the difference was not statistically significant( P>0.05). Adverse reactions: Overall and non-senile observation groups had longer QT interval than control groups( P<0.05), but no patients stopped bedaquiline because of this, and there was no significant difference in QT interval between the two groups( P>0.05). Conclusions:In elderly patients with multi-drug resistant pulmonary tuberculosis, early sputum culture conversion turns fast after treatment with Bedaquiline, which has good therapeutic effect, good tolerance and controllable adverse reactions.

Prevalence of new defined extensive drug resistant tuberculosis in Xi'an / 中国热带医学

@#Abstract: Objective　To collect extensively drug-resistant tuberculosis (XDR-TB) Mycobacterium tuberculosis strains isolated from Xi'an City between 2019 and 2020, and analyze the drug resistance patterns of XDR-TB strains to second-line anti-tuberculosis drugs and the occurrence of new defined extensively drug-resistant tuberculosis in Xi'an, in order to provide evidence for guiding clinical drug use of multidrug-resistant tuberculosis (MDR-TB) patients. Methods A total of 3 088 strains of Mycobacterium tuberculosis that underwent phenotypic drug susceptibility testing at Xi'an Chest Hospital from January 2019 to December 2020 were retrospectively selected to analyze the resistance of anti-tuberculosis drug. Among the stored MDR-TB strains, 114 strains of preserved multidrug-resistant Mycobacterium tuberculosis were randomly selected for bedaquiline and linezolid susceptibility testing. Combined with the results of previous second-line drug susceptibility testing, the incidence of newly defined extensive drug resistance was analyzed. Results Among the 3 088 Mycobacterium tuberculosis strains analyzed, 411 strains (14.3%) showed resistance to isoniazid, 347 strains (11.2%) showed resistance to rifampicin, 142 strains (4.6%) showed resistance to ethambutol, 550 strains (17.8%) showed resistance to streptomycin, and 237 strains (7.6%) exhibited multidrug resistance. Of 237 MDR-TB strains, the resistance rates of ethambutol, moxifloxacin, rifampicin, sodium para-aminosalicylate, prothioconazole, capreomycin, amikacin, and clofazimine were 44.3%, 26.6%, 33.3%, 24.1%, 5.1%, 4.2%, 3.0%, and 2.5%, respectively. Among the randomly selected 114 MDR-TB strains, none showed resistance to bedaquiline, three showed resistance to linezolid, and one strain met the new definition for extensively drug-resistant tuberculosis. Conclusion In Xi'an City, high rates of resistance among MDR-TB strains are observed for ethambutol, quinolone and sodium para-aminosalicylate, and the drug susceptibility tests should be obtained as much as possible when using these drugs. The incidence of new definition extensively drug-resistant tuberculosis is low, and bedaquiline and linezolid remain effective drugs for the treatment of multidrug-resistant tuberculosis even without drug susceptibility testing results.

New insights on tuberculosis transmission dynamics and drug susceptibility profiles among the prison population in Southern Brazil based on whole-genome sequencing

ABSTRACT Background: The rate of tuberculosis (TB) infection among the prison population (PP) in Brazil is 28 times higher than that in the general population, and prison environment favors the spread of TB. Objective: To describe TB transmission dynamics and drug resistance profiles in PP using whole-genome sequencing (WGS). Methods: This was a retrospective study of Mycobacterium tuberculosis cultivated from people incarcerated in 55 prisons between 2016 and 2019; only one isolate per prisoner was included. Information about movement from one prison to another was tracked. Clinical information was collected, and WGS was performed on isolates obtained at the time of TB diagnosis. Results: Among 134 prisoners included in the study, we detected 16 clusters with a total of 58 (43%) cases of M. tuberculosis. Clusters ranged from two to seven isolates with five or fewer single nucleotide polymorphism (SNP) differences, suggesting a recent transmission. Six (4.4%) isolates were resistant to at least one anti-TB drug. Two of these clustered together and showed resistance to rifampicin, isoniazid, and fluoroquinolones, with 100% concordance between WGS and phenotypic drug-susceptibility testing. Prisoners with clustered isolates had a high amount of movement between prisons (two to eight moves) during the study period. Conclusions: WGS demonstrated the recent transmission of TB within prisons in Brazil. The high movement among prisoners seems to be related to the transmission of the same M. tuberculosis strain within the prison system. Screening for TB before and after the movement of prisoners using rapid molecular tests could play a role in reducing transmission.

Drug-Resistant Tuberculosis and COVID-19: A Scoping Review on a New Threat to Antimicrobial Resistance / Tuberculosis Resistente a Medicamentos y COVID-19: Una Revisión de Alcance de una Nueva Amenaza a la Resistencia Antimicrobiana / Tuberculose droga-resistente e COVID-19: revisão de escopo de uma nova ameaça à resistência microbiana a medicamentos

ABSTRACT Objective: To assess the impact of COVID-19 on the morbidity and mortality associated with drug-resistant tuberculosis (DR-TB). Methods: A comprehensive review of articles published in international databases since December 2019 was conducted. The findings are presented in a narrative format, supplemented with tables, diagrams, and a map created using ArcGIS software. Results: Thirty-five studies were selected, highlighting the significant consequences of COVID-19 on TB and DR-TB treatment progress. Four main thematic areas were identified: Clinical and epidemiological aspects of the interaction between COVID-19 and DR-TB; Management of physical resources and the team; Challenges and circumstances; Perspectives and possibilities. Conclusions: This study revealed that the COVID-19 pandemic significantly negatively impacted the control of long-standing diseases like TB, particularly in the context of morbidity and mortality related to DR-TB.

RESUMEN Objetivo: Evaluar el impacto de COVID-19 en la morbilidad y mortalidad asociada con la tuberculosis resistente a medicamentos (DR-TB). Métodos: Se realizó una revisión integral de artículos publicados en bases de datos internacionales desde diciembre de 2019. Los hallazgos se presentaron de forma narrativa, complementados con tablas, diagramas y un mapa creado con el software ArcGIS. Resultados: Se seleccionaron 35 estudios que destacaron las consecuencias significativas de COVID-19 en el progreso del tratamiento de la TB y la DR-TB. Se identificaron cuatro áreas temáticas principales: "Aspectos clínicos y epidemiológicos de la interacción entre COVID-19 y DR-TB", "Gestión de recursos físicos y del equipo", "Desafíos y circunstancias" y "Perspectivas y posibilidades". Conclusiones: Este estudio reveló que la pandemia de COVID-19 tuvo un impacto negativo significativo en el progreso del control de enfermedades antiguas como la TB, especialmente en el contexto de la morbilidad y mortalidad relacionada con la DR-TB.

RESUMO Objetivo: Avaliar o impacto da COVID-19 na morbimortalidade associada à tuberculose resistente a medicamentos (DR-TB). Métodos: Realizou-se uma revisão abrangente de artigos publicados em bases de dados internacionais a partir de dezembro de 2019. As evidências foram apresentadas de maneira narrativa, com o suporte de tabelas, diagramas e um mapa elaborado no software ArcGIS. Resultados: Foram selecionados 35 estudos que destacaram as consequências significativas da COVID-19 nos avanços no tratamento da TB e da DR-TB. Quatro áreas temáticas foram identificadas: "Aspectos clínicos e epidemiológicos da interação entre COVID-19 e DR-TB", "Gestão de recursos físicos e da equipe", "Desafios e circunstâncias" e "Perspectivas e potencialidades". Conclusões: Este estudo evidenciou que a pandemia de COVID-19 teve um impacto negativo significativo na progressão do controle de uma doença ancestral como a TB, especialmente no contexto da morbimortalidade por DR-TB.

The first successful cochlear implant in Latin America after severe aminoglycoside-induced ototoxicity in a Peruvian patient cured of extensively drug-resistant tuberculosis

Introduction: Multidrug-resistant tuberculosis is a significant public health problem for which drugs are used with many adverse effects. Among the devastating consequences of these diseases, there is a wide variation in the incidence of ototoxicity and hearing loss in patients with multidrug-resistant and extremely resistant tuberculosis. Cochlear implants may be indicated in patients with unilateral/severe bilateral hearing loss with no benefit from conventional hearing aids, but their use in patients with tuberculosis is rare. Case report: We present the first case of a right unilateral cochlear implant performed on a 34-year-old Peruvian patient who presented profound sensorineural hearing loss of cochlear origin. Conclusion: Cochlear implant surgery is an essential milestone in the treatment of patients with auditory sequelae of tuberculosis treatment. Close monitoring of possible complications of tuberculosis treatment should be strengthened in countries with a high incidence of multidrug-resistant and extremely resistant tuberculosis.

Introducción: La tuberculosis multidrogorresistente es un importante problema de salud pública para el que se utilizan fármacos con múltiples efectos adversos. Entre las devastadoras consecuencias de estas enfermedades, existe una amplia variación en la incidencia de ototoxicidad y pérdida auditiva en pacientes con tuberculosis multirresistente y extremadamente resistente. Los implantes cocleares pueden estar indicados en pacientes con pérdida auditiva unilateral/bilateral severa sin beneficio de los audífonos convencionales, pero su uso en pacientes con tuberculosis es raro. Reporte de un caso: Presentamos el primer caso de implante coclear unilateral derecho realizado a un paciente peruano de 34 años que presentaba hipoacusia neurosensorial profunda de origen coclear. Conclusión: La cirugía de implante coclear es un hito fundamental en el tratamiento de los pacientes con secuelas auditivas del tratamiento de la tuberculosis. Se debe fortalecer la vigilancia estrecha de las posibles complicaciones del tratamiento de la tuberculosis en los países con una alta incidencia de tuberculosis multirresistente y extremadamente resistente.

Review on Drug Resistant Tuberculosis

Introduction: An estimated 9.9 million people fell ill with tuberculosis globally in 2020 with India and China contribu?ng a major percentage to the burden of TB. India is grouped under high TB, high HIV associated TB and MDR TB burden countries and 1.24 lakh fell ill with drug resistant TB out of which 56000 were started on second line treatment in 2020. Annually India accounts for 27% of missing TB cases. Diagnosis: The major forms of drug resistant TB that are of clinical importance are INH monoresistant TB, mul?drug resistant TB, pre- XDR TB and XDR TB.WHO approved newer molecular tests for MTB detec?on and drug suscep?bility tests. Treatment: Few newer drugs and few previously used drugs are showing promise when used in combina?on which have come up in recent years. Bedaquiline based regimens are showing improved cure rates. Conclusion: Guidelines based regimens should be strictly adhered to by both public and private TB case trea?ng physicians.

Clinical Profile, Adverse Drug Reaction, and Outcome of Category V Patients at a Drug-resistant Tuberculosis Center, Mumbai

Background: Drug regimens for the treatment of drug-resistant tuberculosis (DR-TB) are composed of salvage drugs to which a patient has never been exposed to previously. Methods: A retrospective observational study was conducted in a DR-TB Center attached to a medical college in a metropolitan city using the database of category V patients (n = 100) who were prediagnosed and referred. The clinical records of the patients were reviewed for demographic data, history, sputum examinations, co-morbidities, and adverse drug reactions (ADRs). The therapy outcomes were assessed as per Revised National Tuberculosis Control Programme (RNTCP) guidelines. Results: Their mean age was 29.1 years; there were 57 males. Mean body weight was 41.8 kg. Pediatric patients (age 12�) constituted 13%. All the patients had pulmonary TB. Of the 100 cases, 80 were Category IV failure; 5% were defaulters of Category IV; and 15% were treated with second-line drugs adequately in private. Durg-susceptibility test (DST) showed extensively drug-resistant TB (XDR-TB) in 63 and pre-XDR-TB in 37 patients. The outcomes of Category V treatment were cure (7%), died (33%), failed on therapy (4%), transferred out (16%), lost to follow-up (2%), and still on the therapy (35%). Various comorbidities were present in 25% patients. ADRs were seen in 44%, and peripheral neuropathy (18%) was the most commonly observed ADR. Conclusions: DR-TB patients were younger and males were more affected. Mortality of Category V regimen was high (33%). Most common comorbidities were anemia and hypothyroidism. Adverse reactions were common (44%); ADR peripheral neuropathy being the most common.

Meta-analysis of the adverse effects of drug-resistant tuberculosis drugs on pregnant women and fetuses / 中国药房

OBJECTIVE To systematically evaluate the adverse effects of drug-resistant tuberculosis （DR-TB） drugs on pregnant women and fetuses ，so as to provide evidence-based reference for clinical medication. METHODS PubMed，Cochrane Library，Embase，CBM，CNKI，Wanfang database and VIP were searched by computer to collect randomized controlled trials （RCTs），cohort studies ，case-control studies ，case series and case reports about pregnant women exposed to DR-TB drugs. The retrieval time limit was from the establishment of each database to August 20，2021. After selecting the literature and extracting the data，the bias risk assessment tool recommended by 6.2 version of Cochrane system evaluator manual was used to evaluate the quality of the included RCTs ；Newcastle-Ottawa scale was used to evaluate the quality of the included cohort studies and case-control studies ；IHE scale issued by the Canadian Institute of Health Economics （IHE）was used to evaluate the quality of the included case series and case reports. RevMan 5.1 software was used for Meta-analysis of non-comparative binary data. RESULTS A total of 13 literature were included ，including 7 case series and 6 case reports ，involving 203 patients and 204 newborns；among them，there were 6 literature about non-comparative binary data. The results of meta-analysis showed that after exposure to DR-TB drugs，no newborn had birth defects ；the mortality of pregnant women was 0.09[95％CI（0.06，0.15），P＜0.000 01]；the neonatal mortality was 0.02[95％CI（0，0.06），P＜0.000 01]；the incidence of preterm birth was 0.14[95％CI（0.03，0.43），P＝0.02]；the incidence of infants with low birth weight was 0.17[95％CI（0.04，0.51），P＝0.06]；the incidence of growth retardation was 0.15[95％CI（0.09，0.22），P＜0.000 01]；the incidence of stillbirth was 0.05[95％CI（0.02，0.09），P＜0.000 01]；the incidence of abortion was 0.08[95％CI（0.05，0.14），P＜0.000 01]. CONCLUSIONS Pregnant women exposed to DR-TB drugs can cause pregnant women ’s death and abortion ，neonatal death ，premature birth ，infants with low birth weight ，growth retardation and stillbirth，but there is no neonatal birth defect ；these adverse outcomes may be related to the history of DR-TB.

Changes of cytokine levels before and after anti-tuberculosis treatment / 中国热带医学

@#Abstract： Objective　To analyze the changes of cytokine levels in patients with sensitive pulmonary tuberculosis and drug-resistant pulmonary tuberculosis before and after anti-tuberculosis treatment. Methods　The clinical data of 213 pulmonary tuberculosis patients admitted to the Eighth Affiliated Hospital of Xinjiang Medical University from August 2019 to October 2020 were collected, and divided into a sensitive pulmonary tuberculosis group and a drug-resistant pulmonary tuberculosis group, of which 141 were in the sensitive group and 72 in the drug-resistant group , and the pro-inflammatory factors tumor necrosis factor-α (TNF-α), IL-6, IL-17, interferon-γ (IFN-γ) and anti-inflammatory factors IL-10 and IL-4 in plasma before treatment, 3 months and 6 months after treatment were compared. Results　Compared with the healthy group, the levels of plasma IL-6 in the sensitive group and the resistant group were significantly increased, difference was statistically significant (P<0.01). The plasma levels of IFN-γ and IL-17 in the sensitive group were increased, and the difference was statistically significant (P<0.05). Compared with before treatment, the levels of IL-6 and IL-4 in the plasma of the sensitive group after 6 months of treatment were lower than those after 3 months of treatment, and the difference was statistically significant (P<0.05), and IFN-γ was significantly decreased (P<0.001). After 6 months of treatment, the IL-10 content was lower than that before treatment, and the difference was statistically significant (P<0.05), and the IFN-γ decreased significantly (P<0.000 1). The levels of IFN-γ at 3 months were higher than those in the resistant group, and the difference was statistically significant (P<0.01). After 6 months of treatment, there was no significant difference in the content of IFN-γ between the sensitive group and the resistant group. The effective rate of CT absorption was 70% in the sensitive group and only 43.33% in the resistant group at 3 months of treatment, and there was no significant difference in the effective rate between the two groups after 6 months of treatment. Conclusions　Detection of pro-inflammatory cytokines and anti-inflammatory cytokines in plasma can provide reference for host-directed therapy of pulmonary tuberculosis. Understanding this important feature of cytokines on pathogen-host interactions can provide new insights into the study of virulence mechanisms and may provide new approaches for immune intervention in pulmonary tuberculosis.