Efeitos do adalimumabe, clindamicina e/ou rifampicina no tratamento da hidradenite supurativa: um protocolo de revisão sistemática / Effects of adalimumab, clindamycin, and/or rifampicin in the treatment of hidradenitis suppurativa: a systematic review protocol

OBJETIVO: Avaliar a efetividade, segurança, níveis de dor e qualidade de vida associados ao uso de adalimumabe, clindamicina e/ou rifampicina no tratamento da hidradenite supurativa. MÉTODO: Serão incluídos estudos do tipo coorte prospectiva e retrospectiva, ensaios clínicos randomizados e de equivalência, bem como análises econômicas realizadas com adultos diagnosticados com hidradenite supurativa, que tenham utilizado pelo menos uma das seguintes alternativas terapêuticas: adalimumabe, clindamicina ou rifampicina. Os estudos devem abordar um ou mais desfechos, tais como contagem de abscessos e/ou nódulos, presença de nódulos inflamatórios, níveis de dor, qualidade de vida, segurança e custos. As bases de dados consultadas serão: Medical Literature Analysis and Retrieval System Online (MEDLINE, Interface OVID), Excerpta Medica DataBASE (EMBASE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL, interface EBSCO), Psychological Abstracts (PsycINFO, interface EBSCO), Web of Science (WoS) e Source-Neutral Abstract and Citation Database (Scopus). Os processos de triagem, seleção e extração serão conduzidos por pesquisadores independentes e previamente treinados. O risco de viés será avaliado por meio dos instrumentos Risk of Bias 2.0 e ROBINS-I. Os resultados serão combinados em uma síntese qualitativa e quantitativa, com a realização de análises de especificidade e subgrupos.

OBJECTIVE: To evaluate the efficacy, safety, pain, and quality of life associated with the use of adalimumab, clindamycin, and/or rifampicin in the treatment of hidradenitis suppurativa. METHOD: Prospective and retrospective cohort studies randomized clinical trials and equivalence studies, and economic analyses, conducted in adults diagnosed with hidradenitis suppurativa who have used at least one of the following therapeutic alternatives: adalimumab, clindamycin, or rifampicin, will be included. Studies should address one or more outcomes such as abscess and/or nodule counts, presence of inflammatory nodules, pain levels, quality of life, safety, and cost. Databases consulted will include Medical Literature Analysis and Retrieval System Online (MEDLINE, OVID interface), Excerpta Medica DataBASE (EMBASE), Latin American and Caribbean Literature in Health Sciences (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCO interface), Psychological Abstracts (PsycINFO, EBSCO interface), Web of Science (WoS), and Source-Neutral Abstract and Citation Database (Scopus). Screening, selection, and extraction processes will be conducted by independent and previously trained researchers. The risk of bias will be assessed using the Risk of Bias 2.0 and ROBINS-I tools. Results will be summarized in a qualitative and quantitative synthesis, including specificity and subgroup analyses.

Partial recovery of tuberculosis preventive treatment in Brazil after pandemic drawback / Recuperação parcial do tratamento preventivo da tuberculose no Brasil após o recuo pandêmico / Recuperación parcial del tratamiento preventivo de la tuberculosis en Brasil tras el retroceso pandémico

Abstract: Brazil was heavily affected by COVID-19 both with death toll and economically, with absence of a centralized Federal Government response. Tuberculosis (TB) notifications decreased in 2020 but partial recovery was observed in 2021. We have previously shown a sharp (93%) reduction in TB preventive treatment notifications among five Brazilian cities with more than 1,000 notifications in 2021. We hypothesized TB preventive treatment would also recover. We updated the previous analysis by adding other cities that hold more than a 1,000 notifications until 2022. Data aggregated by 2-week periods were extracted from the Information System for Notifying People Undergoing Treatment for LTBI (IL-TB). Biweekly percentage change (BPC) of notifications until October 2022 and outcomes until July 2022 (in the two weeks of TB preventive treatment initiation) were analyzed using Joinpoint software. A total of 39,701 notifications in 11 cities were included, 66% from São Paulo and Rio de Janeiro, Brazil. We found a significant increase of TB preventive treatment notifications in the beginning of 2021 (BPC range 1.4-49.6), with sustained progression in seven out of the 11 cities. Overall, median completion rates were 65%. In most cities, a gradual and steady decrease of treatment completion rates was found, except for Rio de Janeiro and Manaus (Amazonas State, Brazil), where a BPC of 1.5 and 1.2, respectively, was followed by a sustained increase. Notifications and completion proportions of TB preventive treatment were heterogeneous, which partly reflects the heterogeneity in local response to the pandemic. We found that notifications were recovered, and that the sharp 2021 decrease was no longer observed, which suggests delays in notification. In conclusion, the sharp reductions in TB preventive treatment completion rates in most cities might have been caused by delays in reporting; however, the sustained and progressive decrease are a concern.

Resumo: O Brasil foi fortemente atingido pela COVID-19 tanto com número de mortes quanto economicamente, com ausência de uma resposta centralizada do Governo Federal. As notificações de tuberculose (TB) diminuíram em 2020, mas se recuperaram parcialmente em 2021. Já mostramos uma redução acentuada (93%) nas notificações de tratamento preventivo de TB nas cinco cidades brasileiras com mais de 1.000 notificações em 2021. Hipotetizamos que o tratamento preventivo de TB também recuperar-se-ia. Atualizamos a análise anterior acrescentando outras cidades que apresentaram mais de 1.000 notificações até 2022. Os dados agregados por períodos de duas semanas foram extraídos do Sistema de Informação para Notificação das Pessoas em Tratamento de ILTB (IL-TB). As notificações quinzenais de variação percentual até outubro de 2022 e os desfechos até julho de 2022 (nas duas semanas de início do tratamento precoce de TB) foram analisados usando o software Joinpoint. Foram incluídas 39.701 notificações em 11 cidades, sendo 66% delas de São Paulo e do Rio de Janeiro (Brasil). Encontramos um aumento significativo das notificações de tratamento preventivo de TB no início de 2021 (faixa de variação quinzenal percentual 1,4-49,6), com progressão sustentada em 7/11 cidades. No geral, as taxas medianas de conclusão foram de 65%. Na maioria dos municípios, houve queda gradual e constante das taxas de conclusão de tratamento, com exceção do Rio de Janeiro e Manaus (Amazonas, Brasil), onde a variação quinzenal percentual de 1,5 e 1,2, respectivamente, foi acompanhada de aumento sustentado. As notificações e proporções de tratamento preventivo de TB completados foram heterogêneas, o que reflete em parte a diversidade na resposta local à pandemia. No geral, as notificações se recuperaram e a queda acentuada de 2021 não é mais observada, o que sugere atrasos na notificação. Em conclusão, a redução das taxas de conclusão do tratamento preventivo da TB na maioria das cidades pode refletir atrasos na notificação, mas a diminuição sustentada e progressiva das notificações preocupa.

Resumen: Brasil fue seriamente afectado por el COVID-19, tanto con el número de muertes como económicamente, con la ausencia de una respuesta centralizada del Gobierno Federal. Las notificaciones de la tuberculosis (TB) redujeron en 2020, pero aumentaron parcialmente en 2021. Ya mostramos una reducción drástica (el 93%) en las notificaciones del tratamiento preventivo de la TB en las cinco ciudades brasileñas con más de 1.000 notificaciones en 2021. Nuestra hipótesis es que el tratamiento preventivo de la TB también aumentaría. Actualizamos el análisis anterior añadiendo otras ciudades que presentaron más de 1.000 notificaciones hasta 2022. Los datos agregados durante períodos de dos semanas se extrajeron del Sistema de Información de Notificaciones para Personas en Tratamiento por ILTB (IL-TB). Las notificaciones quincenales de cambio porcentual hasta octubre de 2022 y os resultados hasta julio de 2022 (en las dos semanas iniciales del tratamiento precoz de la tuberculosis) se analizaron a través del software Joinpoint. Se incluyeron 39.701 notificaciones en 11 ciudades, siendo el 66% de ellas en São Paulo y Rio de Janeiro, Brasil. Encontramos un aumento significativo de las notificaciones del tratamiento preventivo de la TB a principios de 2021 (rango de cambio porcentual quincenal 1,4-49,6), con progresión sostenida en siete de las once ciudades. En general, las tasas medias de finalización fueron del 65%. En la mayoría de los municipios, hubo una reducción gradual y constante de las tasas de finalización de tratamiento, salvo en Rio de Janeiro y Manaus (Amazonas, Brasil), donde el cambio porcentual quincenal de 1,5 y 1,2, respectivamente, estuvo acompañado de un aumento sostenido. Las notificaciones y proporciones de cumplimentación del tratamiento preventivo de la TB fueron heterogéneas, lo que refleja la heterogeneidad en la respuesta local a la pandemia. En general, las notificaciones aumentaron y ya no se observa la fuerte caída de 2021 lo que refleja en parte retrasos en la notificación. En conclusión, la reducción en las tasas de finalización del tratamiento preventivo de la TB en la mayoría de las ciudades puede reflejar retrasos en la notificación, pero la reducción sostenida y progresiva es una preocupación.

Avances en tuberculosis en el 54° congreso chileno de enfermedades respiratorias. 1ra parte: nuevos esquemas acortados para tuberculosis drogoresistente ¿son adecuados para todos? / New shortened schemes for drug-resistant tuberculosis: are they suitable for everyone?

En esta presentación se realiza un recorrido a través de los diferentes esquemas terapéuticos de la tuberculosis drogo-resistente. Se muestra como los investigadores utilizan los nuevos fármacos disponibles y desarrollan diferentes esquemas cada vez más acortados y de administración por vía oral exclusiva, con la intención de lograr una mayor eficacia de curación de la tuberculosis resistente, con menos efectos colaterales y menor letalidad. La búsqueda de esquemas con una duración similar a las terapias de casos sensibles de tuberculosis (esquemas primarios de 6 meses) es el objetivo principal. Las pruebas moleculares como el Xpert ayudan enormemente a seleccionar los esquemas de terapia, según el perfil de susceptibilidad de los casos (resistencia a isoniazida, rifampicina, fluorquinolonas y combinaciones). Las terapias actuales de la tuberculosis drogo-resistente se basan en nuevos fármacos como fluorquinolonas, bedaquilina y linezolid, pero otros fármacos como pretomanid y delamanid también están siendo recomendados.

This presentation takes a tour through the different therapeutic schemes of drug-resistant tuberculosis. It shows how researchers use the new drugs available and develop different increasingly shortened schedules and exclusive oral administration, with the intention of achieving greater efficacy in curing resistant tuberculosis, with fewer side effects and lower lethality. The search for regimens with a duration similar to therapies of sensitive cases of tuberculosis (primary regimens of 6 months) is the main objective. Molecular tests, such as Xpert, greatly help in selecting therapy regimens, according to the susceptibility profile of the cases (resistance to isoniazid, rifampicin, fluorquinolones and combinations). Current drug-resistant tuberculosis therapies are based on new drugs such as fluorquinolones, bedaquiline and linezolid, but other drugs such as pretomanid and delamanid are also being recommended.

Lesión renal aguda y anemia hemolítica autoinmune inducida por rifampicina, una complicación poco frecuente y potencialmente mortal

La rifampicina es un medicamento ampliamente utilizado para el tratamiento de diversas infecciones bacterianas con un amplio espectro de efectos adversos que varían desde reacciones leves hasta potencialmente fatales; la anemia hemolítica es un efecto adverso escasamente reportado en la literatura pero que puede tener un desenlace potencialmente fatal, reportamos así un caso de anemia hemolítica autoinmune asociada a lesión renal aguda en una paciente joven en segunda fase de tratamiento para tuberculosis pulmonar.

Summary Rifampicin is a widely used drug for the treatment of various infectious diseases with a broad spectrum of adverse reaction ranging from mild to life-threatening manifestations; hemolytic anemia is an adverse effect rarely reported in the literature, but it can have a potentially fatal outcome. Thus, we report a case of autoimmune hemolytic anemia associated with acute kidney injury in a young patient in the second phase of treatment for pulmonary tuberculosis.

Ten-year experience with penile prosthetic surgery for the treatment of erectile dysfunction: outcomes of a tertiary referral center and predictors of early prosthetic infection / 亚洲男科学杂志(英文版)

We aimed to evaluate ten-year outcomes of penile prosthesis (PP) implantation for the treatment of erectile dysfunction and to assess predictors of early prosthetic infection (EPI). We identified 549 men who underwent 576 PP placements between 2008 and 2018. Univariate and multivariate analyses were used to identify potential predictors of EPI. An EPI predictive nomogram was developed. Thirty-five (6.1%) cases of EPI were recorded with an explant rate of 3.1%. In terms of satisfaction, 82.0% of the patients defined themselves as "satisfied," while partner's satisfaction was 88.3%. Diabetes (P = 0.012), longer operative time (P = 0.032), and reinterventions (P = 0.048) were associated with EPI risk, while postoperative ciprofloxacin was inversely associated with EPI (P = 0.014). Rifampin/gentamicin-coated 3-piece inflatable PP (r/g-c 3IPP) showed a higher EPI risk (P = 0.019). Multivariate analyses showed a two-fold higher risk of EPI in diabetic patients, redo surgeries, or when a r/g-c 3IPP was used (all P < 0.03). We showed that diabetes, longer operative time, and secondary surgeries were the risk factors for EPI. Postoperative ciprofloxacin was associated with a reduced risk of EPI, while r/g-c 3IPP had higher EPI rates without an increased risk of PP explant. After further validation, the proposed nomogram could be a useful tool for the preoperative counseling of PP implantation.

An uncommon case of brucellosis with ocular presentation / Um caso incomum de brucelose com apresentação ocular

ABSTRACT We report an unusual case of brucellosis presented with headache, diminished vision, papillitis and multiple peripapillary hemorrhages accompanied by subretinal fluid extending up to macula. Diagnosis of brucellosis was made based on positive polymerase chain reaction of cerebrospinal fluid sample for Brucella species DNA, accompanied by a raised titer of anti-brucella antibodies. Patient showed remarkable improvement on triple drug therapy in form of doxycycline, rifampicin and ceftriaxone.

RESUMO Relatamos um caso incomum de brucelose apresentada com cefaleia, visão diminuída, papilite e múltiplas hemorragias peripapilares acompanhadas por fluido sub-retinal, estendendo-se até a mácula. O diagnóstico de brucelose foi feito com base na reação em cadeia da polimerase positiva de amostra de líquido cefalorraquidiano para DNA de espécies de Brucella, acompanhada por um título elevado de anticorpos antibrucela. O paciente apresentou melhora notável com a terapia tripla com drogas na forma de doxiciclina, rifampicina e ceftriaxona.

Experience in the diagnosis and treatment of a drug-induced pemphigus / 华西口腔医学杂志

Drug-induced pemphigus (DIP) is a special type of pemphigus, and its pathogenesis, characteristics of treatment, and prognosis are closely related to the inducing drugs. This article reports the diagnosis and treatment of DIP (pemphigus vulgaris) caused by the administration of rifampin to a patient with tuberculosis. Combined with the literature, we discussed the types, pathogenesis, differential diagnosis, and treatment principles of DIP. We propose that in the oral clinical practice for patients with pemphigus vulgaris, the importance of investigating suspected drugs that induce DIP should be emphasized.

Mycolicibacterium fortuitum genomic epidemiology, resistome and virulome

BACKGROUND Mycolicibacterium fortuitum is an opportunistic pathogen associated with human and animal infection worldwide. Studies concerning this species are mainly represented by case reports, some of them addressing drug susceptibility with a focus on a specific geographic region, so there is a gap in relation to the global epidemiological scenario. OBJECTIVES We aimed determine the global epidemiological scenario of M. fortuitum and analyse its traits associated with pathogenicity. METHODS Based on publicly available genomes of M. fortuitum and a genome from Brazil (this study), we performed a genomic epidemiology analysis and in silico and in vitro characterisation of the resistome and virulome of this species. FINDINGS Three main clusters were defined, one including isolates from the environment, human and animal infections recovered over nearly a century. An apparent intrinsic resistome comprises mechanisms associated with macrolides, beta-lactams, aminoglycosides and antitubercular drugs such as rifampin. Besides, the virulome presented Type VII secretion systems (T7SS), including ESX-1, ESX-3, ESX-4 and ESX-4-bis, some of which play a role on the virulence of Mycobacteriaceae species. MAIN CONCLUSIONS Here, M. fortuitum was revealed as a reservoir of an expressive intrinsic resistome, as well as a virulome that may contribute to its success as a global opportunist pathogen.

Cobertura y fidelidad de la prueba Xpert MTB/RIF™ en un área de alta carga de tuberculosis pulmonar en Colombia / Coverage and fidelity of the Xpert MTB/RIF™ implementation in a high-burden area for pulmonary tuberculosis in Colombia

Resumen. Introducción. La prueba Xpert MTB/RIF™ es una prueba molecular rápida para el diagnóstico de la tuberculosis y la resistencia a la rifampicina. Desde el 2010 es la recomendada por la Organización Mundial de la Salud (OMS) y, aunque fue introducida en Colombia en el 2012, se desconocen los resultados de su uso.Objetivo. Describir la cobertura y la fidelidad en el uso de la prueba Xpert MTB/RIF™ en pacientes con tuberculosis pulmonar en una ciudad con alta carga de la enfermedad en Colombia.Materiales y métodos. Se hizo un estudio retrospectivo descriptivo de casos del programa de tuberculosis en Cali entre el 2013 y el 2019. La cobertura se estimó como el total de pruebas empleadas en los casos registrados en el programa. La fidelidad se midió con base en los protocolos internacionales de uso de la Xpert MTB/RIF™. Además, se hizo un análisis de correspondencias múltiples entre la prueba y las variables sociodemográficas.Resultados. Se incluyeron 6.328 pacientes con tuberculosis pulmonar, de los cuales 181 eran resistentes a los fármacos. La cobertura total de la Xpert MTB/RIF™ durante el periodo de estudio fue de 10,3 % (n=655), con una variación anual entre 0,2 y 23 %. La fidelidad fue de 46,8 % para los grupos de mayor riesgo de tuberculosis multirresistente (TB-MDR). El uso de la prueba se relacionó con la condición de ser hombre, afrocolombiano, y tener entre 41 y 60 años de edad.Conclusiones. La cobertura de la prueba Xpert MTB/RIF™ en Cali es baja y su uso no responde a la priorización recomendada para su implementación. Se requieren estrategias para promover su uso adecuado, de manera que contribuya a la meta de poner fin a la tuberculosis.

Abstract. Introduction:The Xpert MTB/RIF™ is a rapid molecular test that diagnoses tuberculosis and rifampin resistance. Since 2010, it is recommended by the World Health Organization (WHO) and although it was introduced in Colombia since 2012, the results of its implementation are unknown.Objective: To describe the coverage and fidelity in the implementation of the Xpert MTB/RIF™ in patients with pulmonary tuberculosis in a city with a high burden for the disease in Colombia.Materials and methods: We conducted a retrospective, descriptive study of cases from a tuberculosis program in Cali between 2013 and 2019. We estimated the coverage as the total number of tests used compared to the cases registered in the program and the fidelity based on international Xpert MTB/RIF™ implementation protocols. We performed a multivariate analysis of multiple correspondences between the test and the sociodemographic variables.Results: We included 6,328 patients with pulmonary tuberculosis of whom 181 were drug-resistant. The Xpert MTB/RIF™ coverage was 10,3% (n=655) with an annual variation between 0.2% and 23%. Loyalty among the highest risk groups of MDR-TB was 46.8%. The use of the test was related to being an Afro-Colombian man between 41 and 60 years of age.Conclusions: The coverage of the Xpert MTB/RIF in Cali is low and its use does not follow the recommended prioritization for its implementation. Implementation strategies are required for its proper use to contribute to the goal of ending tuberculosis.

Acute tubulointerstitial nephritis due to the use of rifampicin. case report

ABSTRACT Introduction: Rifampin is a cornerstone for the first phase of the treatment of pulmonary tuberculosis. This report presents the case of a patient with allergic tubulointerstitial nephritis (ATIN) due to rifampin, situation that has not been reported in Colombia. Case presentation: A male patient with a history of pulmonary tuberculosis treated with rifampin developed acute kidney injury. On admission, no evidence of abnormalities or history to explain the injury was found, but he did present tubular acidosis and associated Fanconi syndrome. The kidney injury was temporarily consistent with rifampicin use, and a kidney biopsy confirmed ATIN. The drug was suspended, resulting in improved kidney function. Discussion: ATIN as a side effect of rifampin is a scarcely reported disease. The risk of developing this condition should be considered when starting and restarting treatments with this medication. Conclusion: ATIN is one of the side effects of tuberculosis treatment. Albeit rare, it should be considered when starting tuberculosis medications.

RESUMEN Introducción. La rifampicina es un medicamento fundamental en la primera fase del tratamiento en la tuberculosis pulmonar; sin embargo, esta puede causar nefritis tubulointersticial aguda (NTIA) en raras ocasiones. Presentación del caso. Paciente masculino con antecedentes de tuberculosis y en tratamiento con rifampicina, quien desarrolló lesión renal aguda. Al ingreso, el sujeto no registró anormalidades o antecedentes que explicaran lesión renal, pero sí presentaba acidosis tubular y síndrome de Fanconi asociado. La lesión renal concordó temporalmente con el uso de rifampicina y una biopsia de riñón confirmó NTIA. Se ordenó suspender el medicamento, con lo cual la función renal mejoró. Discusión. La NTIA como un efecto secundario de la rifampicina es una enfermedad poco reportada, por tanto, al iniciar y al reiniciar el manejo con este medicamento se debe tener en cuenta el riesgo de desarrollarla. Conclusión. La NTIA es uno de los efectos secundarios del tratamiento de la tuberculosis y, aunque es raro, debe tenerse en cuenta al iniciar el esquema de medicamentos para la tuberculosis.

Validación e implementación de GeneXpert MTB/RIF para diagnóstico de tuberculosis en Ecuador / Validation and implementation of GeneXpert MTB/RIF for diagnosis of Tuberculosis in Ecuador

El objetivo del estudio fue la validación e implementación de GeneXpert MTB/RIF para uso rutinario en la detección rápida de tuberculosis, y sensibilidad a la rifampicina en muestras clínicas; para esto se recogieron 1592 muestras respiratorias y fueron analizadas en el laboratorio del Instituto Nacional de Investigación en Salud Pública Guayaquil. El análisis de los resultados de GeneXpert en comparación con la baciloscopía mostraron una sensibilidad inicial de 99,8% y especificidad de 93,2%; el análisis de discrepancias utilizando los resultados del cultivo como método de referencia mostró que los resultados de GeneXpert considerados falsos negativos resultaron ser verdaderos negativos, lo mismo sucede con los falsos positivos que corresponden a verdaderos positivos. Recalculada la sensibilidad y especificidad del GeneXpert se tuvo 99,8% y 100% correspondientemente. La comparación con pruebas de sensibilidad a drogas mostró una sensibilidad de 91,4% y una especificidad del 95,5% para el sistema GeneXpert MTB/RIF. Se concluye que la implementación del sistema GeneXpert en Ecuador permitió dar solución a ciertos problemas asociados con la aplicación de las metodologías de diagnóstico convencionales, disminuyendo los tiempos de espera, e incrementando la sensibilidad y especificidad en el diagnóstico de la tuberculosis resistente a drogas, generando una valiosa oportunidad de diagnóstico temprano.

The objective of the study was the validation and implementation of GeneXpert MTB/RIF for routine use in the rapid detection of tuberculosis and sensitivity to rifampicin in clinical samples; for this, 1592 respiratory samples were collected and analyzed in the laboratory of Instituto Nacional de Investigación en Salud Pública Guayaquil. The analysis of the results of GeneXpert in comparison with smear microscopy showed an initial sensitivity of 99.8% and specificity of 93.2%; The analysis of discrepancies using the results of the culture as a reference method showed that the GeneXpert results considered false negatives turned out to be true negatives, the same happens with the false positives that correspond to true positives. Recalculated the sensitivity and specificity of the Xpert was 99.8% and 100% correspondingly. The comparison with the drugs susceptibility test showed a sensitivity of 91.4% and a specificity of 95.5% for the GeneXpert MTB/RIF system. It is concluded that the implementation of the Xpert system allows solution to certain problems associated with the application of conventional diagnostic methodologies, decreasing the waiting times, and increasing the sensitivity and specificity in the diagnosis of drug-resistant tuberculosis, thus generating a valuable opportunity for early diagnosis.

Nefritis intersticial aguda inducida por rifampicina en un paciente con tuberculosis pulmonar / Rifampicin-induced acute interstitial nephritis in a patient with pulmonary tuberculosis

La tuberculosis (TB) constituye un grave problema de salud en el mundo y está relacionada con problemáticas sociales que dificultan su control y erradicación como la pobreza, la marginalidad y el hacinamiento. Aunque la toxicidad hepática por rifampicina es bien conocida, la nefrotoxicidad es una complicación poco frecuente y grave del tratamiento antituberculosis. El deterioro de la función renal, determinado por nefritis tubulointersticial aguda o necrosis tubular aguda o ambos, por lo general aparece en pacientes que reciben tratamiento intermitente; no obstante, algunos autores han informado casos ocurridos durante la terapia continua con rifampicina.Con frecuencia la lesión renal aguda inducida por rifampicina tiene un curso favorable con tratamiento y una recuperación completa de la función renal en un lapso de tres meses. El siguiente reporte describe un paciente en tratamiento por TB Pulmonar, que desarrolló toxicidad renal inducida por rifampicina

Evaluation of Hepatoprotective Activity of Neem Extract in Rifampin Induced Acute Hepatic Failure in Rats

The liver plays a role in many body functions such as immune defense and the metabolism of sugar and fat. Rifampin (RIF)is an antibacterial drug prescribed to treat tuberculosis (TB) along with multiple drugs. Other types of infections may alsobe treated with rifampin. Although the therapeutic effect of RIF has many adverse effects such as hepatoyoxicity. Neem (NM)has more than 140 compounds from various parts that have been isolated and can thus play a role in preventinghepatotoxicity. The research was carried out to examine the protective effect of neem leaves extract (NMLE) on RIF-inducedliver damage. Forty male rats had been divided into four groups; Group I) non-treated negative control group, (Group II),which was given RIF (54 mg/kg/day) for thirty days, (groups III and IV intoxicated rats received orally the NMLE in dosesof two hundred and fifty and five hundred mg/kg/day respectively, for 30 days. At day 30, blood was collected forbiochemical analysis, as well as the liver was also examined histopathologically. The results revealed that the NMLE at thetwo dosage levels significantly decreased serum levels of liver enzymes and MDA accompanied by significantly increased inactivities of GSH, SOD, and showed ant-inflammatory effects as evidence by significantly decreased in TNF-α and IL-1αlevels compared to RIF group II. There was also an improvement in histopathological alterations observed in liver tissues ofhepatotoxic rats. Therefore, the administrations of NMLE has hepatoprotective effects in hepatotoxic rats via antioxidantand ant-inflammatory pathway.

Clinical application of a new-generation Xpert Mycobacterium tuberculosis/rifampin Ultra cartridge / 中华传染病杂志

Objective To investigate the clinical value of a new-generation cartridge Xpert MTB/RIF Ultra assay on detection of Mycobacterium tuberculosis(MTB)and rifampin(RIF)resistance.Methods A total of 111 patients from He'nan Provincial Chest Hospital with suspected tuberculosis(TB)and retreated TB were enrolled into this study from March to December 2016,including 33 cases of tuberculosis detection group(CDG)and 78 cases of drug resistant high-risk group(DRG).The sputum samples of patients were collected.The sensitivity and specificity of Xpert MTB/RIF Ultra,sputum smear,solid Lowenstein-Jensen(L-J)culture and mycobacterial growth indicator tube(MGIT)culture for MTB were evaluated.RIF resistance was performed by Xpert MTB/RIF Ultra,traditional phenotypic drug sensitivity test and Xpert MTB/RIF assay.Measurement data were compared using t-test,and categorical data were compared using chi-squared test.Results Using clinical diagnosis result as the standard,in the CDG,the sensitivity of Xpert MTB/RIF Ultra for MTB detection(75.8%)was not significantly different from those of sputum smear(66.7%),L-J culture(63.6%),MGIT culture(75.6%)and Xpert MTB/RIF(66.7%)(x2=0.67,1.15,0.00 and 0.67,respectively,all P>0.05).In the DRG,the sensitivity of Xpert MTB/RIF Ultra(94.9%)was better than those of L-J culture(55.1%)and MGIT culture(80.8%)with statistical significance(x2=32.8 and7.25,respectively,both P <0.05).The sensitivity of Xpert MTB/RIF Ultra was not significantly different from sputum smear(84.6%)and Xpert MTB/RIF(91.0%)(x2=3.41 and 0.39,respectively,both P>0.05).Xpert MTB/RIF Ultra took the shortest time to obtain the final results,which was(1.76±0.18)h and significantly shorter than smear test([5.04±0.49]h),L-J culture([31.67±0.56]h),MGIT culture([22.36±9.68]h),Xpert MTB/RIF([2.00±0.30]h)(t=16.90,31.98,24.38 and 7.05,respectively,all P <0.01).Using culture result as the standard,the sensitivity for MTB detection of Xpert MTB/RIF and Xpert MTB/RIF Ultra were 93.2% and 98.9%,and the specificity of Xpert MTB/RIF and Xpert MTB/RIF Ultra were both 100%.The sensitivity for MTB detection of Xpert MTB/RIF Ultra(52.2%)was significantly better than that of Xpert MTB/RIF(21.7%)in 23 smear-negative pulmonary TB patients with statistical significance(x2=4.98,P=0.025).Using traditional drug susceptibility test as the standard,the sensitivities for RIF resistance detection of Xpert MTB/RIF and Xpert MTB/RIF Ultra in culture-positive TB patients were 90.9% and 93.2%,respectively,and the specificities were 89.5% and 92.9%,respectively.Conclusions Xpert MTB/RIF Ultra has a higher MTB detection rate than Xpert MTB/RIF in smear-negative pulmonary TB patients.In drug-resistant pulmonary TB patient,MTB/RIF Ultra has high sensitivity,and it takes shorter time to detect MTB and RIF resistance.Thus,Xpert MTB/RIF Ultra has a good application prospect in clinical work.

Rapid detection of tuberculosis and extrapulmonary rifampicin resistance by GeneXpert / 中国基层医药

Objective@#To investigate the clinical value of GeneXpert in the rapid diagnosis of rifampicin resistance in tuberculosis and extrapulmonary tuberculosis.@*Methods@#From June 2018 to March 2019, a total of 122 tuberculosis patients admitted to the People's Hospital of Yueqing were selected.Among them, 109 patients with pulmonary tuberculosis and 13 patients with extrapulmonary tuberculosis.GeneXpert MTB/RIF, smear, LJ solid medium, BACTEC MGIT 960 liquid medium four detection methods were used to detect tuberculosis secretion.GeneXpert MTB/RIF, LJ solid medium, BACTEC MGIT 960 liquid medium three detection methods were used to detect extrapulmonary tuberculosis secretion.The sensitivity and specificity of GeneXpert MTB/RIF, smear, LJ solid medium, BACTEC MGIT 960 liquid medium for tuberculosis specimens were detected and compared, and the monitoring results of rifampicin resistance in extracorporeal tuberculosis specimens in culture medium detected by GeneXpert MTB/RIF, LJ solid medium, BACTEC MGIT 960 liquid were observed.@*Results@#The GeneXpert MTB/RIF, smear, LJ solid medium, BACTEC MGIT 960 liquid medium were used to detect 109 cases of tuberculosis, and the detection rates were 94.50%(103/109), 55.04%(60/109), 57.79% (63/109), 61.47%(67/109), respectively.The detection rates of extrapulmonary tuberculosis were 7.69%(1/13), 0.00%(0/13) and 15.38%(2/13), respectively.The sensitivity and specificity of the four methods for the diagnosis of tuberculosis had statistically significant differences(χ2=121.540, 127.610, all P<0.05). The diagnostic efficiency of GeneXpert MTB/RIF was significantly better than smear, LJ solid medium, BACTEC MGIT 960 liquid medium.The results of stratification analysis of rifampicin resistance using GeneXpert MTB/RIF, LJ solid medium and BACTEC MGIT 960 liquid medium showed that there were no statistically significant differences among the three methods and gold standard(χ2=0.750, 0.942, 0.947, all P>0.05).@*Conclusion@#GeneXpert technology has the advantages of simple operation, rapid detection and high detection rate.It has high clinical value for the rapid diagnosis of tuberculosis and extrapulmonary specimens and the detection of rifampicin resistance.

Study of effect of rifampin and tanshinone II A on pravastatin transport via BSEP in sandwich-cultured rat hepatocytes / 中国药理学通报

Aim To elucidate the effect of rifampin and tanshinone II A on BSEP transport capacity using pravastatin as the BSEP substrate in sandwich-cultured rat hepatocytes (SCRH). Methods SCRH model was established. The doses of drugs were determined by MIT. A HPLC-MS/MS method was developed and was conducted method validation to detect the concentration of pravastatin. The effect of rifampin and tanshinone D A on the concentration of pravastatin in the bile duct was investigated. And the biliary excretion index ( BEI) was calculated. Results The SCRH model was successfully developed. The appropriate doses of rifampin, tanshinone DA, glibenclamide and pravastatin were determined. A stable and reliable HPLC-MS/MS method for the determination of pravastatin was established Compared with blank control group, rifampin reduced the concentration of pravastatin in the bile duct and the BEI of pravastatin. The high concentration of rifampin caused the steepest downward trends ( P < 0 . 0 1 ) . Compared with high concentration group of rifampin, the concentration of pravastatin in the bile duct and the BEI of pravastatin gradually increased after the combination of rifampin and tanshinone II A, and the effect of high concentration of tanshinone II A was the most significant ( P < 0. 0 1 ) . Conclusions Rifampin could inhibit the function of BSEP in SCRH. The combination of tanshinone D A and rifampin could reverse the inhibitor)' effect of BSEP transport capacity caused by rifampin.

Influence of rifampin in effectiveness of antihypertensive drugs in patients with hypertension: A case report and literature review / 吉林大学学报(医学版)

Objective: To discuss the diagnosis and treatment process of abnormally elevated blood pressure in the patient treated with rifampicin and antihypertensive drugs, to analyze the interaction between rifampicin and antihypertensive drugs, and to improve the clinicians' understanding of the administration in the patients. Methods: The clinical materials of a patient treated with rifampicin and antihypertensive drugs were collected, and the relationship between the blood pressure change and drug was analyzed. The changes of concentrations of dihydropyridine-based calcium antagonists after administration of rifampin were observed and the relative literatures were reviewed. Results: A 58-year-old man with coughing and coughing for 1 month was admitted to hospital. The patient was definitely diagnosed as tuberculosis and hypertension before admission; the patient was treated with rifampicin, isoniazid, ethambutol, pyrazinamide, and felodipine together. The original treatment plan was continued and the blood pressure of the patient was monitored. On the 9th day of anti-tuberculosis treatment, the patient developed dizziness, chest tightness, and severe fluctuations in blood pressure. Then rifampicin was stopped and antihypertensive drugs were adjusted. At the beginning of blood pressure fluctuation of the patient, the combination of angiotensin-converting enzyme inhibitors and the increasing dose of dihydropyridine-based calcium antagonists did not control the blood pressure. The blood pressure began to decrease significantly at 36 h after rifampin was stopped. On the 18th day of anti-tuberculosis treatment, the original antihypertensive plan was restored and the blood pressure remained stable. Conclusion: Rifampicin can sometimes significantly reduce the effect iveness of antihypertensive drugs (such as dihydropyridine calcium antagonists), and the clinicians should pay attention to it.

Simultaneous determination of isoniazid and rifampin in tuberculosis patients by uplc-ms/ms / 中国药学杂志

OBJECTIVE: To establish an UPLC-MS/MS method for the determination of isoniazid and rifampin in tuberculosis patients. METHODS: The blood protein was precipitated by methanol after adding acetaminophen as internal standard, chromatography separation was performed on Thermo Syncronis C18 column (2.1 mm×100 mm,1.7 μm), gradient elution was conducted using methanol and acetic acid aqueous solution(0.1%) as mobile phase, and MS/MS was used for detection. RESULTS: The correlation coefficients were greater than 0.999 0 for isoniazid in the range of 0.05-5 μg•mL-1 and rifampin in the range of 0.01-10 μg•mL-1, the recoveries were 100.5%-102.5% and 92.0%-96.4%, the limits of detection were 0.05 and 0.01 μg•mL-1, and the relative standard deviations (RSDs) were 0.5%-4.3% and 1.1%-3.9%, respectively. CONCLUSION: The established internal standard method can simultaneously detect rifampin and isoniazid with good specificity, high sensitivity, reproducibility and accuracy, which can be used to determine the blood concentrations of rifampin and isoniazid in tuberculosis patients.

Fluconazol como alternativa terapéutica en infecciones asociadas a Mycobacterium tuberculosis / Fluconazole as a therapeutic alternative in infections associated with Mycobacterium tuberculosis

Mycobacterium tuberculosis (M. tuberculosis) es un microorganismo cuya importancia como agente infeccioso ha permanecido a través de los años, pero que se ha convertido en una emergencia y un grave problema de salud pública, como respuesta a la evolución en su comportamiento ante los antimicrobianos de primera línea para su tratamiento y al surgimiento de cepas multi-resistentes, lo que amerita el uso de alternativas terapéuticas que permitan su control. El objetivo del trabajo fue evaluar el comportamiento in vitro de M. tuberculosis ante el antimicótico fluconazol, para su posible uso como alternativa terapéutica. Para ello, se evaluaron 6 cepas de M. tuberculosis: 2 resistentes a rifampicina, 2 resistentes a isoniazida y 2 sensibles a ambos antimicrobianos, Se utilizó el método de Concentración Inhibitoria Mínima, utilizando la técnica en microplaca con Azul de Alamar y la técnica de dilución en tubo. Ambas metodologías mostraron sensibilidad ante bajas concentraciones de fluconazol (0,0625 µg/ml). Todas las cepas fueron sensibles a la combinación fluconazol/isoniazida; mientras que, a la combinación fluconazol/rifampicina mostraron resistencia, indicando el efecto antagónico de la rifampicina sobre el fluconazol. Los resultados permiten concluir y sugerir el posible uso terapéutico del fluconazol ante las infecciones asociadas por M. tuberculosis.

Mycobacterium tuberculosis (M. tuberculosis) is a microorganism whose importance as an infectious agent has remained over the years but which has become a recent emergency and a serious public health problem in response to the evolution in its behavior against first-line antimicrobials, for its treatment and the emergence of multi-resistant strains, which require the use of therapeutic alternatives that allow its control. The objective of the work was to evaluate the in vitro behavior of M. tuberculosis before the antifungal agent fluconazole, for its possible use as a therapeutic alternative. To this, six strains were evaluated M. tuberculosis: 2 resistants to rifampicin, 2 resistants to isoniazid and 2 sensitive to both antimicrobials. We used the method of Minimum Inhibitory Concentration, using the microplate technique with Alamar Blue and the tube technique. Both methodologies showed sensitivity to low concentrations of fluconazole (0.0625 µg/ml). All strains were sensitive to the fluconazole / isoniazid combination; whereas, when exposed to the fluconazole / rifampicin combination, the strains showed resistance, indicating the antagonistic effect of rifampicin on fluconazole. The results allow us to conclude and suggest the possible therapeutic use of fluconazole against infections associated with M. tuberculosis.

Trombocitopenia inducida por rifampicina / Rifampicin-induced thrombocytopenia

RESUMEN La trombocitopenia inducida por rifampicina es un fenómeno de origen inmune cuya presentación es inusual pero potencialmente fatal. Se presenta el caso de un paciente inmunocomprometido y con tuberculosis diseminada quien desarrolló trombocitopenia inducida por rifampicina en las primeras 12 horas tras inicio de la terapia antituberculosa sin que mediara sensibilización previa al medicamento. Se confirmó la relación de causa-efecto al resolverse la trombocitopenia con la suspensión de la rifampicina y al reaparecer con la re-exposición al fármaco.

SUMMARY Rifampicin-induced thrombocytopenia is a rare but potentially fatal immune phenomenon. We report the case of an immunocompromised patient with disseminated tuberculosis who developed rifampicin-induced thrombocytopenia 12 hours after starting anti-tuberculous therapy without previous drug sensitization. The cause-effect relationship was confirmed when thrombocytopenia resolved with rifampicin suspension but later reappeared upon drug re-exposure.