Tuberculosis farmacorresistente en provincia Guantánamo, 2010-2019 / Drug-resistant tuberculosis in Guantánamo province, 2010-2019 / Tuberculose resistente a medicamentos na província de Guantánamo, 2010-2019

RESUMEN Introducción: En los últimos 10 años en Cuba y, especialmente, en provincia Guantánamo se ha observado incremento del número de pacientes tuberculosos farmacorresistentes; esta es la provincia de mayor incidencia en el país. Objetivo: Identificar las características epidemiológicas y el patrón de resistencia de la tuberculosis farmacorresistente en provincia Guantánamo. Método: Se diseñó un estudio descriptivo y transversal que incluyó la totalidad de casos (n=6) con tuberculosis farmacorresistentes diagnosticados entre diciembre de 2010 y diciembre de 2019. Se estudiaron las variables: edad, sexo, régimen terapéutico, situación económica, categorías de casos, clasificación epidemiológica de la resistencia y resistencia de la cepa aislada según el grado y perfil. Resultados: Predominó el sexo masculino (66, 6 %) y el grupo de edades de menores de 45 años (83,3 %), la mayor cantidad de resistencia estuvo propiciada por violaciones en los tratamientos anteriores (66,6 %), categorizados mayormente como crónicos y reingresos por abandono. Predominó el nivel educacional de secundaria básica terminada (66,7 %), con situación económica regular (50,0 %) y alto nivel de alcoholismo (66,7 %). La multidrogorresistencia prevaleció en cepas de pacientes con tratamiento previo (66,6 %). Conclusiones: Existe coincidencia del patrón epidemiológico y el patrón de resistencia mostrado en la investigación actual con los resultados de estudios previos nacionales e internacionales, estos resultados sugieren fallas en la aplicación local del Programa Nacional de Control y Tratamiento de la tuberculosis. Se recomienda investigar y resolver estas fallas lo que produciría un impacto inmediato en la disminución de la incidencia de tuberculosis farmacorresistentes.

ABSTRACT Introduction: An increase in the number of drug-resistant tuberculosis patients has been observed in the last 10 years in Cuba and, especially, in Guantánamo province. This is the province with the highest incidence in the country. Objective: To identify the epidemiological characteristics and the resistance pattern of drug-resistant tuberculosis in Guantánamo province. Method: A descriptive, cross-sectional study was designed that included all cases (n=6) with drug-resistant tuberculosis, diagnosed between December 2010 and December 2019. The variables studied were: age, gender, therapeutic regimen, economic situation, categories of cases, epidemiological classification of resistance, and resistance of the isolated strain according to the grade and profile. Results: Males predominated (66.6%), and also the age group under 45 years (83.3%), the greatest resistance was caused by not abiding the previous treatments (66.6%), categorized mostly as chronic, and readmitted due to treatment abandonment. Highschool degree (66.7%) predominated, with a moderate economic situation (50.0%) and high levels of alcoholism (66.7%). Multi-drug resistance prevailed in the strains in patients with previous treatment (66.6%). Conclusions: There is a coincidence of the epidemiological pattern and the resistance pattern shown in the current research with the results of previous national and international studies; these results suggest flaws in the local application of the Programa Nacional de Control y Tratamiento de la tuberculosis. It is recommended to investigate and resolve these flaws, which would have an immediate impact on reducing the incidence of drug-resistant tuberculosis.

RESUMO Introdução: Nos últimos 10 anos, em Cuba e, principalmente, na província de Guantánamo, observou-se um aumento no número de pacientes com tuberculose resistente aos medicamentos; esta é a província com maior incidência no país. Objetivo: Identificar as características epidemiológicas e o padrão de resistência da tuberculose resistente a medicamentos na província de Guantánamo. Método: Foi elaborado um estudo descritivo e transversal que incluiu todos os casos (n=6) com tuberculose resistente a medicamentos diagnosticados entre dezembro de 2010 e dezembro de 2019. Foram estudadas as variáveis: idade, sexo, regime terapêutico, situação econômica, categorias de casos, classificação epidemiológica de resistência e resistência da cepa isolada de acordo com o grau e perfil. Resultados: Houve predomínio do sexo masculino (66,6%) e na faixa etária abaixo de 45 anos (83,3%), a maior quantidade de resistência foi causada por violações nos tratamentos anteriores (66,6%), categorizados principalmente como crônicos e reinternações por abandono. Predominou situação econômica regular (50,0%) e alto nível de alcoolismo (66,7%). A multirresistência prevaleceu em cepas de pacientes com tratamento anterior (66,6%). Conclusões: Há coincidência do padrão epidemiológico e do padrão de resistência mostrado na pesquisa atual com os resultados de estudos nacionais e internacionais anteriores, esses resultados sugerem falhas na aplicação local do Programa Nacional de Controle e Tratamento da Tuberculose. Recomenda-se investigar e resolver essas falhas, que teriam um impacto imediato na redução da incidência de tuberculose resistente aos medicamentos.

Prevalence and Clinical Features of Drug Reactions With Eosinophilia and Systemic Symptoms Syndrome Caused by Antituberculosis Drugs: A Retrospective Cohort Study

PURPOSE: Although there have been reported cases of drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome caused by antituberculosis drugs, there has been no research to examine its prevalence. This study assessed the prevalence and clinical characteristics of DRESS syndrome caused by antituberculosis drugs. METHODS: The electronic medical records of a cohort consisting of adult patients diagnosed with tuberculosis between July 2006 and June 2010 were reviewed and retrospectively inspected. We searched the surveillance system for adverse drug reactions and the electronic medical records to identify patients who reported severe cutaneous adverse reactions to antituberculosis drugs. These patients were then re-assessed using a European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) scoring system. Clinical characteristics, including the symptoms and latency of DRESS syndrome, the therapeutic dosage and period of steroids, and the final duration of tuberculosis therapy, were examined. RESULTS: Of the 1,253 adult patients with tuberculosis receiving antituberculosis drugs, 15 were identified as potential cases of DRESS syndrome (prevalence of 1.2%). Ethambutol was the most frequently used drug (53.5%), followed by rifampicin (26.7%), pyrazinamide (20.0%), streptomycin (13.3%), and isoniazid (6.7%). The median latency after day 1 of antituberculosis medication was 42 days. The median daily dose of steroids, expressed in prednisone-equivalent units, was 33-mg/day, and the median dosing period was 14 days. The duration of tuberculosis treatment was 76 days longer than the standard treatment period of 180 days. There was a significant difference in the peak eosinophil counts of DRESS syndrome patients according to RegiSCAR scores. Moreover, there was a significant quantitative correlation between the RegiSCAR score and peak eosinophil count. A negative correlation was also found between the RegiSCAR score and latency. CONCLUSIONS: This study confirmed the prevalence of DRESS syndrome in a cohort of adult patients with tuberculosis.

Antimicrobial Susceptibility and Genetic Analysis of Campylobacter jejuni Isolated from Diarrhea Patients in Busan / 대한임상미생물학회지

BACKGROUND: Campylobacter jejuni is an important food-borne pathogen that causes human gastroenteritis. This study was conducted to investigate the incidence of isolation, antimicrobial susceptibility pattern, and C. jejuni genotype from diarrhea patients in Busan, Korea. METHODS: A total of 97 C. jejuni were isolated from diarrhea patients during five food-borne outbreaks from 2014 to September 2017. Antimicrobial susceptibility tests were carried out by the broth microdilution method for ciprofloxacin (CIP), nalidixic acid (NAL), tetracycline (TET), chloramphenicol, azithromycin (AZI), erythromycin (ERY), streptomycin (STR), gentamicin, and telithromycin. To investigate C. jejuni genotypes, pulsed-field gel electrophoresis (PFGE) profile analysis was performed. RESULTS: The isolation rate of C. jejuni was 2.0% for the last 4 years and increased annually. Antimicrobial resistance rates of C. jejuni were shown to be in the order of NAL (90.9%), CIP (89.4%), TET (13.6%), AZI (3.0%), ERY (3.0%), and STR (1.5%). The proportion of multidrug-resistance was 18.2%, and they commonly contained quinolones (CIP-NAL). Analysis of PFGE patterns of SmaI-restricted DNA of C. jejuni isolates showed 17 clusters; cluster 11 was the major genotype pattern. CONCLUSION: This study will provide useful data for the proper use of antimicrobials and the management of resistant C. jejuni. Also it will help to provide data for the epidemiological investigation of foodborne diseases caused by C. jejuni, which is expected to increase in the future.

Evaluation of in vitro antimicrobial susceptibility of Bacillus anthracis strains isolated during anthrax outbreaks in Italy from 1984 to 2017

Anthrax, caused by Bacillus anthracis, is a non-contagious infectious disease that affects a wide range of animal species (primarily ruminants) including humans. Due to the often-fatal outcome in humans, quick administration of definitely effective antimicrobials is crucial either as prophylaxis or as a clinical case therapy. In this study, 110 B. anthracis strains, temporally, geographically, and genetically different, isolated during anthrax outbreaks in Italy from 1984 to 2017, were screened using a broth microdilution method to determine their susceptibility to 16 clinically relevant antimicrobial agents. The strains were isolated from various matrices (human, animal, and environmental samples) and were representative of thirty distinct genotypes previously identified by 15-loci multiple-locus variable-number of tandem repeats analysis. The antimicrobials tested were gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline, and trimethoprim. All isolates were susceptible to most of the tested antimicrobials, with the exception of trimethoprim for which all of them showed high minimal inhibitory concentration values. An intermediate level of susceptibility was recorded for ceftriaxone and cefotaxime. Although the Centers for Disease Control and Prevention recommend the use of doxycycline, ciprofloxacin, penicillin G, and amoxicillin for treatment of human cases and for post-exposure prophylaxis to anthrax spores, this study shows a high degree of in vitro susceptibility of B. anthracis to many other antimicrobials, suggesting the possibility of an alternative choice for prophylaxis and therapy.

Sinal de Faget como manifestação clínica de brucelose. Relato de caso / Faget's sign as a clinical manifestation of brucellosis: Case report

Relata-se o caso de uma paciente do sexo feminino, 32 anos, comerciante, com manifestações sistêmicas de brucelose, como febre diária contínua, sinal de Faget, lombalgia, cervicalgia, náuseas e cefaleia. Quando questionada, a paciente referiu consumo de leite e queijo não pasteurizados de origem bovina. Nos exames laboratoriais, foram evidenciados leucocitose, linfopenia, proteína C-reativa dentro dos parâmetros da normalidade e ausência de transaminasemia, contrapondo achados clássicos da doença. Os exames de imagem mostraram sinais característicos de sacroileíte. O tratamento foi realizado com doxiciclina 100mg via oral a cada 12 horas e estreptomicina 1g via intramuscular diária. O resultado da titulação para brucelose foi positivo. A paciente teve boa resposta ao tratamento, mantendo-se afebril e em bom estado geral até a alta hospitalar, que ocorreu após 14 dias do início da medicação, tendo sido mantido o tratamento ambulatorialmente. (AU)

A case of a 32-year-old female retailer with systemic manifestations of brucellosis, such as prolonged daily fever, Faget's sign, low back and neck pain, nausea and headache. When questioned, the patient reported consumption of unpasteurized milk and cheese of bovine origin. Laboratory tests revealed leukocytosis, lymphopenia, normal levels of C-reactive protein, and absence of transaminasemia, contrasting classic findings of the disease Imaging evaluation showed characteristic signs of sacroiliitis. The treatment was performed with doxycycline 100mg orally every 12 hours, and streptomycin 1g intramuscularly once daily. The serology for brucellosis was positive. The patient showed good response to the treatment, remaining afebrile and in good general condition until hospital discharge, which took place 14 days after starting the medication; she remained on treatment in an outpatient setting. (AU)

The role of the Xpert MTB/RIF assay among adolescents suspected of pulmonary tuberculosis in Rio de Janeiro, Brazil

Abstract INTRODUCTION The teste rápido molecular para tuberculose (TRM-TB) was introduced in 2014 in Brazil for tuberculosis screening. However, its role in adolescents in Brazil has not been studied. METHODS A descriptive study of adolescents with suspected tuberculosis using National Laboratory software. RESULTS Of 852 (15.4%) suspected cases, 131 were positive by TRM-TB and 2% were resistant to rifampicin. Among TRM-TB-positive cases, 105 (91.4%) were culture-positive. Sixty-four of 96 samples were sensitive to rifampicin by TRM-TB; 11 were resistant to other drugs by drug sensitivity test (DST). CONCLUSIONS Among suspected cases, 16% were diagnosed by TRM-TB, of which 17% were drug-resistant by DST.

Determining Genotypic Drug Resistance by Ion Semiconductor Sequencing With the Ion AmpliSeq™ TB Panel in Multidrug-Resistant Mycobacterium tuberculosis Isolates

BACKGROUND: We examined the feasibility of a full-length gene analysis for the drug resistance-related genes inhA, katG, rpoB, pncA, rpsL, embB, eis, and gyrA using ion semiconductor next-generation sequencing (NGS) and compared the results with those obtained from conventional phenotypic drug susceptibility testing (DST) in multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates. METHODS: We extracted genomic DNA from 30 pure MDR-TB isolates with antibiotic susceptibility profiles confirmed by phenotypic DST for isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA), amikacin (AMK), kanamycin (KM), streptomycin (SM), and fluoroquinolones (FQs) including ofloxacin, moxifloxacin, and levofloxacin. Enriched ion spheres were loaded onto Ion PI Chip v3, with 30 samples on a chip per sequencing run, and Ion Torrent sequencing was conducted using the Ion AmpliSeq TB panel (Life Technologies, USA). RESULTS: The genotypic DST results revealed good agreement with the phenotypic DST results for EMB (Kappa 0.8), PZA (0.734), SM (0.769), and FQ (0.783). Agreements for INH, RIF, and AMK+KM were not estimated because all isolates were phenotypically resistant to INH and RIF, and all isolates were phenotypically and genotypically susceptible to AMK+KM. Moreover, 17 novel variants were identified: six (p.Gly169Ser, p.Ala256Thr, p.Ser383Pro, p.Gln439Arg, p.Tyr597Cys, p.Thr625Ala) in katG, one (p.Tyr113Phe) in inhA, five (p.Val170Phe, p.Thr400Ala, p.Met434Val, p.Glu812Gly, p.Phe971Leu) in rpoB, two (p.Tyr319Asp and p.His1002Arg) in embB, and three (p.Cys14Gly, p.Asp63Ala, p.Gly162Ser) in pncA. CONCLUSIONS: Ion semiconductor NGS could detect reported and novel amino acid changes in full coding regions of eight drug resistance-related genes. However, genotypic DST should be complemented and validated by phenotypic DSTs.

An Imported Case of Brucella melitensis Infection in South Korea

Brucellosis is a zoonotic infection that is usually transmitted from cattle to humans through ingestion of animal milk, direct contact with animal parts, or inhalation of aerosolized particles. In Korea, brucellosis seem to be transmitted through close contact with blood, fetus, urine, and placenta of domestic cow that has been infected by Brucella abortus, or inhalation of B. arbortus while examining or slaughtering cow. Brucella melitensis infection is rare in Korea and there have been no reported cases of B. melitensis originating from other countries until now. This report details a case of complicated brucellosis with infective spondylitis in a 48-year-old male construction worker recently returned from Iraq. Infection with B. melitensis was confirmed using 16s rRNA sequencing and omp31 gene analysis. The patient was successfully treated using a combination of rifampin, doxycycline, and streptomycin, in accordance with WHO guidelines. This is the first reported case of complicated brucellosis with infective spondylitis in Korea caused by B. melitensis originating from Iraq.

Genotypic Diversity of Multidrug Resistant Shigella species from Iran

BACKGROUND: In many developing countries, shigellosis is endemic and also occurs in epidemics and treatment of multidrug-resistant (MDR) isolates are important. The aims of this study were to determine the antimicrobial susceptibility, prevalence of class 1 and 2 integrons and the clonal relatedness of isolates. MATERIALS AND METHODS: Antimicrobial susceptibility tests were performed by disc diffusion method. Polymerase chain reaction (PCR)-sequencing technique was employed for detection and characterization of integrons. The genetic relatedness was evaluated by using enterobacterial repetitive intergenic consensus (ERIC) PCR. RESULTS: There was a high percentage of resistance to trimethoprim-sulfamethoxazole (TMP/SMX) (93.7%), ampicillin (AMP) (87.3%), streptomycin (STR) (84.5%) and tetracycline (TET) (78.9%). Multidrug resistant phenotype was seen in 95.1% of total isolates. Most common MDR profile was TMP/SMX/STR/AMP resistant pattern. Among the 142 Shigella spp. analyzed in this study, 28 isolates were positive for class 1 integron with two types of gene cassette arrays (dfrA17/aadA5 = 31.7% and dfrA7 = 3.8%). The class 2 integron was more frequently detected among the isolates (94.7%) with dfrA1/sat1/aadA1 (69.4%) and dfrA1/sat1 (30.6%) gene cassettes. ERIC-PCR results showed 6, 5, 4 and 3 main genotypes among S. flexneri, S. sonnei, S. boydii and S. dysenteriae isolates, respectively. CONCLUSIONS: Our findings revealed that multidrug resistant Shigella species with high prevalence of class 2 integron were very common in Iran. In addition, ERIC-PCR patterns showed limited variety of clones are responsible for shigellosis in the region of the study.

An Imported Case of Brucella melitensis Infection in South Korea

Brucellosis is a zoonotic infection that is usually transmitted from cattle to humans through ingestion of animal milk, direct contact with animal parts, or inhalation of aerosolized particles. In Korea, brucellosis seem to be transmitted through close contact with blood, fetus, urine, and placenta of domestic cow that has been infected by Brucella abortus, or inhalation of B. arbortus while examining or slaughtering cow. Brucella melitensis infection is rare in Korea and there have been no reported cases of B. melitensis originating from other countries until now. This report details a case of complicated brucellosis with infective spondylitis in a 48-year-old male construction worker recently returned from Iraq. Infection with B. melitensis was confirmed using 16s rRNA sequencing and omp31 gene analysis. The patient was successfully treated using a combination of rifampin, doxycycline, and streptomycin, in accordance with WHO guidelines. This is the first reported case of complicated brucellosis with infective spondylitis in Korea caused by B. melitensis originating from Iraq.

Genotypic Diversity of Multidrug Resistant Shigella species from Iran

BACKGROUND: In many developing countries, shigellosis is endemic and also occurs in epidemics and treatment of multidrug-resistant (MDR) isolates are important. The aims of this study were to determine the antimicrobial susceptibility, prevalence of class 1 and 2 integrons and the clonal relatedness of isolates. MATERIALS AND METHODS: Antimicrobial susceptibility tests were performed by disc diffusion method. Polymerase chain reaction (PCR)-sequencing technique was employed for detection and characterization of integrons. The genetic relatedness was evaluated by using enterobacterial repetitive intergenic consensus (ERIC) PCR. RESULTS: There was a high percentage of resistance to trimethoprim-sulfamethoxazole (TMP/SMX) (93.7%), ampicillin (AMP) (87.3%), streptomycin (STR) (84.5%) and tetracycline (TET) (78.9%). Multidrug resistant phenotype was seen in 95.1% of total isolates. Most common MDR profile was TMP/SMX/STR/AMP resistant pattern. Among the 142 Shigella spp. analyzed in this study, 28 isolates were positive for class 1 integron with two types of gene cassette arrays (dfrA17/aadA5 = 31.7% and dfrA7 = 3.8%). The class 2 integron was more frequently detected among the isolates (94.7%) with dfrA1/sat1/aadA1 (69.4%) and dfrA1/sat1 (30.6%) gene cassettes. ERIC-PCR results showed 6, 5, 4 and 3 main genotypes among S. flexneri, S. sonnei, S. boydii and S. dysenteriae isolates, respectively. CONCLUSIONS: Our findings revealed that multidrug resistant Shigella species with high prevalence of class 2 integron were very common in Iran. In addition, ERIC-PCR patterns showed limited variety of clones are responsible for shigellosis in the region of the study.

Treatment-failure tularemia in children / 소아과

PURPOSE: Tularemia is an infection caused by Francisella tularensis. Its diagnosis and treatment may be difficult in many cases. The aim of this study was to evaluate treatment modalities for pediatric tularemia patients who do not respond to medical treatment. METHODS: A single-center, retrospective study was performed. A total of 19 children with oropharyngeal tularemia were included. RESULTS: Before diagnosis, the duration of symptoms in patients was 32.15±17.8 days. The most common lymph node localization was the cervical chain. All patients received medical treatment (e.g., streptomycin, gentamicin, ciprofloxacin, and doxycycline). Patients who had been given streptomycin, gentamicin, or doxycycline as initial therapy for 10–14 days showed no response to treatment, and recovery was only achieved after administration of oral ciprofloxacin. Response to treatment was delayed in 5 patients who had been given ciprofloxacin as initial therapy. Surgical incision and drainage were performed in 9 patients (47.5%) who were unresponsive to medical treatment and were experiencing abcess formation and suppuration. Five patients (26.3%) underwent total mass excision, and 2 patients (10.5%) underwent fine-needle aspiration to reach a conclusive differential diagnosis and inform treatment. CONCLUSION: The causes of treatment failure in tularemia include delay in effective treatment and the development of suppurating lymph nodes.

Protective effect of Allium cepa (onion) seeds (AC) extract on histopathology of testis in STZ-induced male rats / Efecto protector del extracto de semillas de Allium cepa (cebolla) (AC) en la histopatología del testículo en ratas macho inducidas por STZ

SUMMARY: The aim of the present study was to evaluate the effect of the extract of Allium cepa (Onion) seeds (AC) on morphometric and histology of testis and biochemical parameters in STZ-induced male rats. Forty adult male Wistar rats (2 month old) were allocated into four groups of control, diabetic control, diabetic treated with 200 or 400 mg/kg/day of onion seed extract. Diabetes mellitus was induced using 60 mg/kg body weight of Streptozotocin as a single intraperitoneal injection. The extract was administered by stomach gavage for 28 days. The morphometric and histological structure of the testis, biochemical factors like glucose and testosterone levels were assessed. All analyses were done at the end of the four week study period. Data were compared by using Kruskal Wallis Test, Dunnett T3 and the degree of significance was set at P < 0.05 and P < 0.01. In diabetic+200 rats, the numbers of primary spermatocytes were significantly increased. In diabetic+400 rats, seminiferous tubular diameter was significantly increased and the level of testosterone hormone and testis weight was decreased significantly. In diabetic+200 and 400 rats, the numbers of spermatid, FBS and lumen diameter were significantly increased and the numbers of spermatozoa cells, body weight and volume density (VD) % lumen were decreased. Also, the numbers of spermatid in control diabetic rats was decreased. Our finding indicated that onion seed extract might be useful as a supplementary protective agent against adverse effects of diabetes on reproductive system in diabetic men.

RESUMEN: El objetivo del presente estudio fue evaluar el efecto del extracto de semillas de Allium cepa (cebolla) sobre la morfometría e histología de testículos y parámetros bioquímicos en ratas macho inducidas por estreptozotocina (STZ). Se asignaron cuarenta ratas macho Wistar adultas (2 meses de edad) en cuatro grupos: control diabético y diabético tratados con 200 o 400 mg / kg / día de extracto de semilla de cebolla. Se indujo diabetes mellitus utilizando 60 mg/kg de peso corporal de estreptozotocina por inyección única intraperitoneal. El extracto se administró por sonda gástrica durante 28 días. Se evaluaron la estructura morfométrica e histológica de los testículos, factores bioquímicos como la glucosa y los niveles de testosterona. Todos los análisis se realizaron al final del período de estudio de cuatro semanas. Los datos se compararon mediante el uso de Kruskal Wallis Test, Dunnett T3 y el grado de significación se estableció en P <0,05 y P <0,01. En el grupo diabético + 200, el número de espermatocitos primarios aumentó significativamente. En el grupo diabético + 400, el diámetro tubular seminífero aumentó significativamente en cambio el nivel de testosterona y el peso del testículo disminuyeron significativamente. En el grupo diabéticos + 200 y 400, los números de espermátidas, FBS y diámetro de luz se incrementaron significativamente y el número de espermatozoides, peso corporal y densidad de volumen (VD)% de lumen disminuyeron. Además, disminuyó el número de espermátidas en ratas diabéticas control. Nuestro estudio indicó que el extracto de semilla de cebolla podría ser útil como un agente protector adicional contra los efectos adversos de la diabetes en el sistema reproductivo en hombres diabéticos.

The importance of audiometric monitoring in patients with multidrug-resistant tuberculosis

Abstract INTRODUCTION: A total of 771 cases of multidrug-resistant tuberculosis (MDR-TB) were reported in Brazil in 2014. Treatment of MDR-TB with aminoglycosides can produce serious side effects such as permanent and irreversible hearing loss, which occurs in 5-64% of cases, and severely compromise patient quality of life. The goal of this research was to evaluate auditory and vestibular side effects in patients treated for MDR-TB and to identify associations between these complaints and the type of aminoglycoside used. METHODS: We performed a retrospective review of 599 medical records from patients with MDR-TB who were treated at the Hélio Fraga/Fiocruz Reference Center between 2006 and 2010. Cases without auditory or vestibular complaints and patients who were not treated with aminoglycoside drugs were excluded from the study. RESULTS: Of 164 eligible cases, 55 (33.5%) reported an auditory or vestibular complaint and medication was subsequently suspended, although hearing damage was not confirmed in all cases. Audiometric testing confirmed hearing loss in 11 (21.7%) of 12 cases submitted for evaluation. Hearing loss related to ototoxicity was confirmed in 15 (62.5%) cases. Tinnitus was significantly associated with the use of amikacin and streptomycin. CONCLUSIONS: Evaluations of ototoxicity symptoms were not usually reported in the routine care of patients with MDR-TB. Complaints of tinnitus were associated with amikacin and streptomycin use. These results require confirmation in future studies.

Evaluation of the commercial kit SIRE nitratase for detecting resistant mycobacterium tuberculosis in Brazil

Abstract INTRODUCTION: This study aimed to evaluate a new commercial kit, Kit SIRE Nitratase-PlastLabor, for testing the drug susceptibility of clinical Mycobacterium tuberculosis isolates. METHODS: The accuracy of the Kit SIRE Nitratase was evaluated by examining the susceptibility (streptomycin, isoniazid, rifampicin, and ethambutol) of 40 M. tuberculosis isolates, using the proportion method with Lowenstein-Jensen medium or the BACTEC MGIT 960 system. RESULTS: The detection accuracy for streptomycin, isoniazid, rifampicin, and ethambutol was 95%, 97.5%, 100%, and 80%, respectively. CONCLUSIONS: The exceptional accuracy demonstrated by Kit SIRE Nitratase for isoniazid and rifampicin makes the kit an attractive option for screening M. tuberculosis strain resistance.

Ampliação de uso dos medicamentos doxiciclina, estreptomicina e rifampicina para o tratamento da brucelose humana / Extension of use of the drugs doxycycline, streptomycin and rifampicin for the treatment of human brucellosis

CONTEXTO: No período de 2013 a 2016 foram registrados no Sistema de Informação de Agravos de Notificação (SINAN), 1.493 notificações de brucelose humana e observou-se que a partir de 2015, houve um aumento considerável no número de notificações. Esse comportamento crescente reforça a necessidade de implementação de ações específicas, incluindo a implantação de um sistema de vigilância e a garantia de acesso a diagnóstico e tratamento adequados e oportunos. Considerando que o Ministério da Saúde já adquire doxiciclina, rifampicina e estreptomicina para atender à demanda de outros programas (tuberculose e hanseníase, por exemplo), este relatório visa avaliar a ampliação de uso dos referidos medicamentos no SUS, para tratamento da brucelose humana. TECNOLOGIAS: Doxiciclina 100mg comprimido; sulfato de estreptomicina 1g pó para solução injetável; rifampicina 300mg cápsula; e rifampicina 20mg/mL suspensão oral. INDICAÇÃO: Brucelose humana. PERGUNTA: O uso da doxiciclina, rifampicina e estreptomicina é eficaz e seguro para o tratamento de pacientes com brucelose humana? EVIDÊNCIAS CIENTÍFICAS: Foram selecionadas três revisões sistemáticas que embasaram a recomendação de ampliação de uso dos medicamentos avaliados e, em geral, os resultados demonstraram que, na comparação de doxiciclina+rifampicina versus doxiciclina+estreptomicina, para os desfechos avaliados, não houve diferença entre os grupos. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário da ampliação de uso dos tratamentos analisados para a brucelose humana será entre R$ 26.046,72 e R$ 31.473,12 por ano, dependendo da percentagem de pacientes que seguirá cada um dos esquemas de tratamento analisados. Estes valores representam um aumento de 2,9% a 3,5% nos valores gastos na última compra feita pelo Ministério da Saúde. CONSIDERAÇÕES FINAIS: Com base nos resultados das revisões sistemáticas apresentadas, sugere-se que inicialmente seja recomendada a ampliação de uso dos seguintes medicamentos que já estão incluídos na Rename, para tratamento da brucelose humana: (i) doxiciclina 100mg comprimido; (ii) sulfato de estreptomicina 1g pó para solução injetável; (iii) rifampicina 300mg cápsula; e (iv) rifampicina 20mg/mL suspensão oral. RECOMENDAÇÃO DA CONITEC: os membros da CONITEC, presentes na 52ª reunião ordinária, realizada nos dias 1e 2 de fevereiro de 2017, deliberaram por unanimidade recomendar a ampliação de uso dos medicamentos doxiciclina, estreptomicina e rifampicina para tratamento de brucelose humana. DECISÃO: Ampliar o uso dos medicamentos doxiciclina, estreptomicina e rifampicina para tratamento da brucelose humana, no âmbito do Sistema Único de Saúde - SUS. A decisão foi dada pela Portaria SCTIE-MS nº 13 publicada no Diário Oficial da União (DOU) nº 50, de 14 de março de 2017, pág. 53.(AU)

Ampliação de uso dos medicamentos doxiciclina, estreptomicina e rifampicina para o tratamento da brucelose humana / Expansion of use of the drugs doxycycline, streptomycin and rifampicin for the treatment of human brucellosis

Contexto: No período de 2013 a 2016 foram registrados no Sistema de Informação de Agravos de Notificação (SINAN), 1.493 notificações de brucelose humana e observou-se que a partir de 2015, houve um aumento considerável no número de notificações. Esse comportamento crescente reforça a necessidade de implementação de ações específicas, incluindo a implantação de um sistema de vigilância e a garantia de acesso a diagnóstico e tratamento adequados e oportunos. Considerando que o Ministério da Saúde já adquire doxiciclina, rifampicina e estreptomicina para atender à demanda de outros programas (tuberculose e hanseníase, por exemplo), este relatório visa avaliar a ampliação de uso dos referidos medicamentos no SUS, para tratamento da brucelose humana. Pergunta: O uso da doxiciclina, rifampicina e estreptomicina é eficaz e seguro para o tratamento de pacientes com brucelose humana? Evidências científicas: Foram selecionadas três revisões sistemáticas que embasaram a recomendação de ampliação de uso dos medicamentos avaliados e, em geral, os resultados demonstraram que, na comparação de doxiciclina+rifampicina versus doxiciclina+estreptomicina, para os desfechos avaliados, não houve diferença entre os grupos. Avaliação de Impacto Orçamentário: O impacto orçamentário da ampliação de uso dos tratamentos analisados para a brucelose humana será entre R$ 26.046,72 e R$ 31.473,12 por ano, dependendo da percentagem de pacientes que seguirá cada um dos esquemas de tratamento analisados. Estes valores representam um aumento de 2,9% a 3,5% nos valores gastos na última compra feita pelo Ministério da Saúde. Considerações finais: Com base nos resultados das revisões sistemáticas apresentadas, sugere-se que inicialmente seja recomendada a ampliação de uso dos seguintes medicamentos que já estão incluídos na Rename, para tratamento da brucelose humana: (i) doxiciclina 100mg comprimido; (ii) sulfato de estreptomicina 1g pó para solução injetável; (iii) rifampicina 300mg cápsula; e (iv) rifampicina 20mg/mL suspensão oral. Recomendação da Conitec: os membros da CONITEC, presentes na 52ª reunião ordinária, realizada nos dias 1 e 2 de fevereiro de 2017, deliberaram por unanimidade recomendar a ampliação de uso dos medicamentos doxiciclina, estreptomicina e rifampicina para tratamento de brucelose humana. Decisão: Ampliar o uso dos medicamentos doxiciclina, estreptomicina e rifampicina para tratamento da brucelose humana, no âmbito do Sistema Único de Saúde - SUS. A decisão foi dada pela Portaria SCTIE - MS nº 13 publicada no Diário Oficial da União (DOU) nº 50, de 14 de março de 2017.

Caracterización de aislamientos clínicos de Mycobacterium tuberculosis obtenidos de individuos positivos para HIV en Colombia, 2012 / Characterization of clinical isolates of Mycobacterium tuberculosis from HIV positive individuals in Colombia, 2012

Resumen Introducción: Una tercera parte de los casos nuevos de tuberculosis se atribuye a la propagación del HIV. En 2012, se presentaron en Colombia 1.397 casos de tuberculosis concomitante con la infección por HIV, es decir, 11,8 % del total de notificados. El uso de las herramientas de epidemiología molecular contribuye a una mejor comprensión de la transmisión de la enfermedad. Objetivo: Caracterizar los aislamientos clínicos de Mycobacterium tuberculosis de individuos positivos para HIV recibidos en el Laboratorio Nacional de Referencia del Instituto Nacional de Salud. Materiales y métodos: Se hizo un estudio observacional descriptivo. Se estudiaron 63 aislamientos de individuos con tuberculosis e infección por HIV mediante pruebas de identificación, sensibilidad y genotipificación. Resultados: Dos de los casos nuevos (3,3 %) eran resistentes a rifampicina y uno (1,6 %) a isoniacida, en tanto que tres (5,0 %) lo eran a la isoniacida combinada con estreptomicina. Los casos previamente tratados fueron sensibles. No se evidenció multirresistencia. Hubo 20 (31,7 %) aislamientos de la familia genética LAM9, 8 (12,7 %) de la H1 y 7 (11,1 %) de la T1 . Diecinueve aislamientos correspondieron a patrones huérfanos. Se observó un único agrupamiento entre los aislamientos analizados. No se encontraron diferencias estadísticamente significativas entre la resistencia a fármacos y las familias genéticas. Conclusión: La resistencia encontrada demostró la transmisión de cepas resistentes a rifampicina e isoniacida. Las familias genéticas LAM9, T1 y H1 corresponden a las descritas en la población general. No se evidenció transmisión activa en los aislamientos estudiados. Se necesitan estudios más completos para conocer la situación real de la infección concomitante de tuberculosis y HIV en el país.

Abstract Introduction: One third of the increase in tuberculosis cases is attributed to the spread of HIV. In 2012, 1,397 HIV-associated tuberculosis cases were reported in Colombia, i.e., 11.8% of the total cases. Molecular epidemiology tools help to understand the transmission of tuberculosis. Objective: To characterize clinical isolates of Mycobacterium tuberculosis derived from HIV-infected individuals, received at the Laboratorio Nacional de Referencia in the Instituto Nacional de Salud. Materials and methods: This was a descriptive observational study. We analyzed 63 isolates of M. tuberculosis from HIV-infected individuals. Identification, drug susceptibility and genotyping assays were performed. Results: Of the new cases evaluated, three (5.0%) were resistant to isoniazid combined with streptomycin; two (3.3%) to rifampicin, and one (1.6%) to isoniazid. Previously treated cases were sensitive. No multidrug resistance was evident. Among the predominant genotypes, 20 isolates were (31.7%) LAM9, eight (12.7%), H1, and seven (11.1%), T1. Nineteen isolates corresponded to orphan patterns. One single grouping was observed among tested isolates. We found no statistically significant difference between the proportions of the antituberculous drug resistance and genotypes. Conclusion: We found resistant isolates to the most powerful drugs, rifampicin and isoniazid, among new cases, showing the transmission of resistant strains. Genetic families of M. tuberculosis LAM9, T1 and H1 correspond to those described in the general population. We detected no active transmission among studied isolates. More comprehensive studies are needed to assess the real situation of HIV associated tuberculosis in the country regarding sensitivity and transmission.

Characteristics of Drug Resistant Tuberculosis in Sanatoria of North Korea

Although several reports about drug-resistant tuberculosis (TB) in North Korea have been published, a nationwide surveillance on this disease remains to be performed. This study aims to analyze the drug resistance patterns of Mycobacterium tuberculosis among the patients in the sanatoria of North Korea, especially during the period when second-line drugs (SLDs) had not yet been officially supplied to this country. The Eugene Bell Foundation (EBF) transferred 947 sputum specimens obtained from 667 patients from 2007 to 2009 to the Clinical Research Center, Masan National Tuberculosis Hospital (MNTH), South Korea. Four hundred ninety-two patients were culture positive for TB (73.8%). Drug susceptibility test (DST) was performed for the bacilli isolated from 489 patients. Over 3 quarters of the cases (76.9%) were multidrug-resistant (MDR)-TB. Additionally, 2 patients had extremely drug-resistant (XDR)-TB. Very high resistance to first-line drugs and low resistance to fluoroquinolones (FQs) and injectable drugs (IDs) except for streptomycin (S) were detected. A small but significant regional variation in resistance pattern was observed. Big city regions had higher rate of MDR-TB, higher resistance to FQs and IDs than relatively isolated regions. In conclusion, significant number of drug-resistant TB was detected in North Korean sanatoria, and small but significant regional variations in resistance pattern were noticeable. However, the data in this study do not represent the nationwide drug resistance pattern in North Korea. Further large-scale evaluations are necessary to estimate the resistance pattern of TB in North Korea.

Mutations in Streptomycin Resistance Genes and Their Relationship to Streptomycin Resistance and Lineage of Mycobacterium tuberculosis Thai Isolates / 결핵및호흡기질환

BACKGROUND: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. METHODS: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. RESULTS: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (pC, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. CONCLUSION: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.