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We investigated the value of plasma cytokine levels as markers of pathogenesis and treatment response in patients with non-tuberculous mycobacteria (NTM) pulmonary disease. Plasma cytokine levels were measured and compared among patients with NTM pulmonary disease (n=111), tuberculosis (TB) patients (n=50), and healthy individuals (n=40). Changes during treatment were monitored at 3 and 6 months after treatment. According to the treatment response, NTM patients were classified as 'resistance' or 'sensitivity' responders. The results revealed that five out of twelve cytokines exhibited significantly higher levels in NTM patients compared to controls. Among these, interleukin (IL)-6 demonstrated the strongest discriminating capacity for NTM. Furthermore, when combined with IL-1ß, they efficiently distinguished between NTM drug-resistant and drug-sensitive patients, as well as between NTM and TB groups. Additionally, IL-6 levels initially rose and then decreased in the NTM drug-resistant group during the six months of treatment, similar to the behavior of IL-1ß in the NTM drug-sensitive group. Subgroup analyses of the sensitive group with differential treatment responses revealed an increase in IL-10 levels in the six-month treatment responders. A high IL-6/IL-10 ratio was associated with increased disease severity of NTM and TB. Collectively, combinations of various plasma cytokines, specifically IL-1ß, IL-6, and IL-10, effectively distinguished NTM patients with varying mycobacterial burdens, with IL-6 and IL-10 emerging as potential biomarkers for early treatment response. The combination of IL-6 and IL-1ß demonstrated the highest discriminatory value for distinguishing between NTM-resistant and NTM-sensitive groups as well as between NTM and TB groups.
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Biomarcadores , Citocinas , Infecciones por Mycobacterium no Tuberculosas , Humanos , Femenino , Masculino , Biomarcadores/sangre , Infecciones por Mycobacterium no Tuberculosas/sangre , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Citocinas/sangre , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Anciano , Resultado del Tratamiento , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Micobacterias no Tuberculosas , Interleucina-6/sangre , Interleucina-1beta/sangreRESUMEN
Introduction: The Mycobacterium chelonae species and the M. avium and M. abscessus complexes are emerging pathogens that cause mycobacteriosis. Treatment depends on the species and subspecies identified. The drugs of choice are macrolides and aminoglycosides. However, due to the resistance identified to these drugs, determining the microbe's sensitivity profile will allow clinicians to improve the understanding of the prognosis and evolution of these pathologies. Objective: To describe the macrolide and aminoglycoside susceptibility profile of cultures identified by Colombia's Laboratorio Nacional de Referencia de Mycobacteria from 2018 to 2022, as Mycobacterium avium complex, M. abscessus complex, and M. chelonae. Materials and methods. This descriptive study exposes the susceptibility profile to macrolides and aminoglycosides of cultures identified as M. avium complex, M. abscessus complex, and M. chelonae using the GenoType® NTM-DR method. Materials and methods: This descriptive study exposes the susceptibility profile to macrolides and aminoglycosides of cultures identified as M. avium complex, M. abscessus complex, and M. chelonae using the GenoType® NTM-DR method. Results: We identified 159 (47.3 %) cultures as M. avium complex, of which 154 (96.9 %) were sensitive to macrolides, and 5 (3.1 %) were resistant; all were sensitive to aminoglycosides. From the 125 (37.2 %) cultures identified as M. abscessus complex, 68 (54.4 %) were sensitive to macrolides, 57 (45.6 %) were resistant to aminoglycosides, and just one (0.8 %) showed resistance to aminoglycosides. The 52 cultures (15.5 %) identified as M. chelonae were sensitive to macrolides and aminoglycosides. Conclusions: The three studied species of mycobacteria have the least resistance to Amikacin. Subspecies identification and their susceptibility profiles allow the establishment of appropriate treatment schemes, especially against M. abscessus.
Introducción. Mycobacterium chelonae y los complejos Mycobacterium avium y M. abscessus, son agentes patógenos emergentes causantes de micobacteriosis. El tratamiento de esta infección depende de la especie y la subespecie identificadas. Los fármacos de elección son los macrólidos y aminoglucósidos, contra los cuales se ha reportado resistencia; por esta razón, el determinar el perfil de sensibilidad le permite al médico tratante comprender mejor el pronóstico y la evolución de estas infecciones. Objetivo. Describir los perfiles de sensibilidad ante macrólidos y aminoglucósidos, de los cultivos identificados como complejo Mycobacterium avium, complejo M. abscessus o especie M. chelonae, en el Laboratorio Nacional de Referencia de Micobacterias durante los años 2018 a 2022. Materiales y métodos. Se llevó a cabo un estudio descriptivo del perfil de sensibilidad a macrólidos y aminoglucósidos, de los cultivos identificados como complejo M. avium, complejo M. abscessus o M. chelonae, mediante la metodología GenoType® NTM-DR. Resultados. Los cultivos del complejo M. avium fueron 159 (47,3 %), de los cuales, 154 (96,9 %) fueron sensibles y 5 (3,1 %) resistentes a los macrólidos; todos fueron sensibles a los aminoglucósidos. Del complejo M. abscessus se estudiaron 125 (37,2 %) cultivos, 68 (54,4 %) resultaron sensibles y 57 (45,6 %) resistentes a los macrólidos; solo un cultivo (0,8 %) fue resistente a los aminoglucósidos. De M. chelonae se analizaron 52 cultivos (15,5 %), todos sensibles a los macrólidos y aminoglucósidos. Conclusiones. En las tres especies de micobacterias estudiadas, la resistencia contra la amikacina fue la menos frecuente. La identificación de las subespecies y los perfiles de sensibilidad permiten instaurar esquemas de tratamiento adecuados, especialmente en las micobacteriosis causadas por M. abscessus.
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Aminoglicósidos , Macrólidos , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Complejo Mycobacterium avium , Mycobacterium chelonae , Macrólidos/farmacología , Mycobacterium abscessus/efectos de los fármacos , Mycobacterium abscessus/genética , Mycobacterium abscessus/aislamiento & purificación , Colombia/epidemiología , Mycobacterium chelonae/efectos de los fármacos , Mycobacterium chelonae/genética , Mycobacterium chelonae/aislamiento & purificación , Aminoglicósidos/farmacología , Humanos , Complejo Mycobacterium avium/efectos de los fármacos , Complejo Mycobacterium avium/genética , Complejo Mycobacterium avium/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Prevalencia , Farmacorresistencia Bacteriana MúltipleRESUMEN
Species belonging to the Mycobacterium kansasii complex (MKC) are frequently isolated from humans and the environment and can cause serious diseases. The most common MKC infections are caused by the species M. kansasii (sensu stricto), leading to tuberculosis-like disease. However, a broad spectrum of virulence, antimicrobial resistance and pathogenicity of these non-tuberculous mycobacteria (NTM) are observed across the MKC. Many genomic aspects of the MKC that relate to these broad phenotypes are not well elucidated. Here, we performed genomic analyses from a collection of 665 MKC strains, isolated from environmental, animal and human sources. We inferred the MKC pangenome, mobilome, resistome, virulome and defence systems and show that the MKC species harbours unique and shared genomic signatures. High frequency of presence of prophages and different types of defence systems were observed. We found that the M. kansasii species splits into four lineages, of which three are lowly represented and mainly in Brazil, while one lineage is dominant and globally spread. Moreover, we show that four sub-lineages of this most distributed M. kansasii lineage emerged during the twentieth century. Further analysis of the M. kansasii genomes revealed almost 300 regions of difference contributing to genomic diversity, as well as fixed mutations that may explain the M. kansasii's increased virulence and drug resistance.
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Genoma Bacteriano , Genómica , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium kansasii , Filogenia , Mycobacterium kansasii/genética , Mycobacterium kansasii/clasificación , Mycobacterium kansasii/aislamiento & purificación , Humanos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Animales , Virulencia/genéticaRESUMEN
Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available. Herein, we report that molecules for binding to the catalytic site of histone deacetylase (HDAC) inhibit its activity, thus increasing the innate immune response against environmental mycobacteria. The action of HDAC inhibitors (iHDACs) was explored in a model of type II pneumocytes and macrophages infection by Mycobacterium aurum. The results show that the use of 1,3-diphenylurea increases the expression of the TLR-4 in M. aurum infected MDMs, as well as the production of defb4, IL-1ß, IL-12, and IL-6. Moreover, we observed that aminoacetanilide upregulates the expression of TLR-4 together with TLR-9, defb4, CAMP, RNase 6, RNase 7, IL-1ß, IL-12, and IL-6 in T2P. Results conclude that the tested iHDACs selectively modulate the expression of cytokines and antimicrobial peptides that are associated with reduction of non-tuberculous mycobacteria infection.
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Citocinas , Reposicionamiento de Medicamentos , Inhibidores de Histona Desacetilasas , Inmunidad Innata , Infecciones por Mycobacterium no Tuberculosas , Inmunidad Innata/efectos de los fármacos , Humanos , Infecciones por Mycobacterium no Tuberculosas/inmunología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Inhibidores de Histona Desacetilasas/farmacología , Citocinas/metabolismo , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Micobacterias no Tuberculosas/efectos de los fármacos , Micobacterias no Tuberculosas/inmunología , Mycobacterium/inmunología , Mycobacterium/efectos de los fármacosRESUMEN
Emerald tree boas (Corallus batesii) are boids that in situ occurs in forested habitats in the Amazon Basin. The mycobacterial species can infect reptiles but the species Mycolicibacterium fortuitum was identified only in feces samples of ex situ Python regius and was isolated from granulomatous lesions of an ex situ Iguana iguana when was still part of the genus Mycobacterium. This article aims to report a mycobacteria infection case in a female Corallus batesii kept under human care. The animal presented apathy and 2 months of anorexia, being found dead. The necropsy revealed presence of tracheal and pulmonary nodules besides multifocal, bacterial, granulomatous pneumonia. After Fite-Faraco histochemical staining, immunohistochemistry, semi-nested polymerase chain reaction (PCR) and genetic sequencing the Mycolicibacterium fortuitum complex was diagnosed with 99.54% of nucleotide similarity. This mycobacterial species was already pointed out as an important nosocomial pathogen and more studies are necessary to explore their zoonotic potential.
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Boidae , Mycobacterium fortuitum , Animales , Femenino , Mycobacterium fortuitum/aislamiento & purificación , Mycobacterium fortuitum/genética , Mycobacterium fortuitum/clasificación , Boidae/microbiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/veterinaria , Resultado Fatal , FilogeniaRESUMEN
Mycobacterium abscessus is an intrinsically drug-resistant, rapidly growing, nontuberculous mycobacterium; extrapulmonary infections have been reported in association with medical tourism (1). During November-December 2022, two Colorado hospitals (hospitals A and B) treated patient A, a Colorado woman aged 30-39 years, for M. abscessus meningitis. In October 2022, she had received intrathecal donor embryonic stem cell injections in Baja California, Mexico to treat multiple sclerosis and subsequently experienced headaches and fevers, consistent with meningitis. Her cerebrospinal fluid revealed neutrophilic pleocytosis and grew M. abscessus in culture at hospital A. Hospital A's physicians consulted hospital B's infectious diseases (ID) physicians to co-manage this patient (2).
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Brotes de Enfermedades , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Colorado/epidemiología , Adulto , Femenino , México/epidemiología , Mycobacterium abscessus/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Arizona/epidemiología , Trasplante de Células MadreRESUMEN
Pseudomycetomas are rare fungal subcutaneous infections caused by dermatophytes, which are mainly observed in immunocompromised patients. Mycobacterium genavense is considered an opportunistic pathogen in people living with HIV/AIDS (PLWHA), clinically resembling the presentation of Mycobacterium avium complex (MAC). Here, we describe the case of a 26-year-old PLWHA with a 3-month history of a 4cm tumoral, duroelastic and painful lesion located on the back. Histopathology of the tumoral lesion revealed chronic granulomatous inflammation with grains composed of PAS-positive and Grocott-positive septate hyphae, as well as acid-fast bacilli (AFB). Culture on Sabouraud and lactrimel agar developed colonies that were later identified as Microsporum canis. In successive samples, the AFB were identified as M. genavense by restriction analysis of PCR products. Immunocompromised PLWHA not only suffer increased susceptibility to diseases due to unusual pathogens but also atypical clinical presentation of frequently encountered pathogens.
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Microsporum , Humanos , Adulto , Microsporum/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Masculino , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Micetoma/microbiología , Infecciones por VIH/complicaciones , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Huésped InmunocomprometidoRESUMEN
Tuberculosis (TB) and infectious diseases caused by non-tuberculous mycobacteria (NTM) are global concerns. The development of a rapid and accurate diagnostic method, capable of detecting and identifying different mycobacteria species, is crucial. We propose a molecular approach, the BiDz-TB/NTM, based on the use of binary deoxyribozyme (BiDz) sensors for the detection of Mycobacterium tuberculosis (Mtb) and NTM of clinical interest. A panel of DNA samples was used to evaluate Mtb-BiDz, Mycobacterium abscessus/Mycobacterium chelonae-BiDz, Mycobacterium avium-BiDz, Mycobacterium intracellulare/Mycobacterium chimaera-BiDz, and Mycobacterium kansasii-BiDz sensors in terms of specificity, sensitivity, accuracy, and limit of detection. The BiDz sensors were designed to hybridize specifically with the genetic signatures of the target species. To obtain the BiDz sensor targets, amplification of a fragment containing the hypervariable region 2 of the 16S rRNA was performed, under asymmetric PCR conditions using the reverse primer designed based on linear-after-the-exponential principles. The BiDz-TB/NTM was able to correctly identify 99.6% of the samples, with 100% sensitivity and 0.99 accuracy. The individual values of specificity, sensitivity, and accuracy, obtained for each BiDz sensor, satisfied the recommendations for new diagnostic methods, with sensitivity of 100%, specificity and accuracy ranging from 98% to 100% and from 0.98 to 1.0, respectively. The limit of detection of BiDz sensors ranged from 12 genome copies (Mtb-BiDz) to 2,110 genome copies (Mkan-BiDz). The BiDz-TB/NTM platform would be able to generate results rapidly, allowing the implementation of the appropriate therapeutic regimen and, consequently, the reduction of morbidity and mortality of patients.IMPORTANCEThis article describes the development and evaluation of a new molecular platform for accurate, sensitive, and specific detection and identification of Mycobacterium tuberculosis and other mycobacteria of clinical importance. Based on BiDz sensor technology, this assay prototype is amenable to implementation at the point of care. Our data demonstrate the feasibility of combining the species specificity of BiDz sensors with the sensitivity afforded by asymmetric PCR amplification of target sequences. Preclinical validation of this assay on a large panel of clinical samples supports the further development of this diagnostic tool for the molecular detection of pathogenic mycobacteria.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium tuberculosis , Micobacterias no Tuberculosas , Reacción en Cadena de la Polimerasa , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/clasificación , Sensibilidad y Especificidad , ARN Ribosómico 16S/genética , Tuberculosis/diagnóstico , Tuberculosis/microbiología , ADN Bacteriano/genética , Técnicas Biosensibles/métodosRESUMEN
As micobactérias não tuberculosas (MNT) são pertencentes ao gênero Mycobacterium da família Mycobacteria-ceae. Esse boletim é um estudo descritivo, de abordagem quatitativa, realizado a partir de dados secundários oriundos do Sistema de Informação de Tratamentos Especiais de Tuberculose (SITE-TB) do Ministério d Saúde (MS)
Nontuberculous mycobacteria (NTM) belong to the genus Mycobacterium of the Mycobacteria-ceae family. This bulletin is a descriptive study, with a quantitative approach, carried out using secondary data from the Tuberculosis Special Treatments Information System (SITE-TB) of the Ministry of Health (MS)
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Humanos , Infecciones por Mycobacterium no Tuberculosas/epidemiologíaRESUMEN
BACKGROUND: The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. METHODS: This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. RESULTS: Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. CONCLUSIONS: This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.
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Infecciones por VIH , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium tuberculosis , Tuberculosis , Animales , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Micobacterias no Tuberculosas , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Estudios Retrospectivos , Mycobacterium leprae , Panamá/epidemiología , Tuberculosis/complicaciones , Infecciones por VIH/complicacionesRESUMEN
Introduction. Disease caused by non-tuberculous mycobacteria (NTM) is an emergent problem. Because NTM pulmonary disease and tuberculosis (TB) have similar clinical presentations, many cases of NTM may be misdiagnosed as TB before laboratory identification of the NTM species.Hypothesis/Gap Statement. Clinical laboratories should always perform differentiation between Mycobacterium tuberculosis complex (MTBC) and NTM to guide patients' correct treatment.Aim. To describe the characteristics and to identify mycobacterial isolates presumptively classified as MTBC by macroscopic characteristics in culture media that tested negative in GenoType MTBDRplus.Methodology. All cultures from February 2019 to December 2021 showing MTBC macroscopic characteristics were processed by GenoType MTBDRplus. MTBC-negative cultures underwent species identification by immunochromatography, line probe assays and PRA-hsp65. Patients' data were obtained from Brazilian surveillance systems.Results. Only 479 (3.1%) of 15â696 isolates presumptively identified as MTBC were not confirmed by GenoType MTBDRplus and were then subjected to identification. A total of 344 isolates were shown to be NTM, of which 309 (64.5%) and 35 (7.3%) were identified to the species and genus levels, respectively. Of the 204 NTM isolates with MTBC characteristics, the most frequent species were M. fortuitum (n=52, 25.5%), M. abscessus complex (MABC; n=27, 13.2%) and M. avium complex (MAC; n=26, 12.7%). Regarding the GenoType MTBDRplus results from NTM isolates, there were diverse hybridisation profiles with rpoB gene's different wild-type (WT) probes. Seventy-six (16.1%) of the 473 patients were classified as having NTM disease, the most frequent being MAC (n=15, 19.7%), MABC (n=13, 17.1%), M. kansasii (n=10, 13.2%) and M. fortuitum (n=6, 7.9%).Conclusion. Because the signs and symptoms of pulmonary TB are similar to those of pulmonary mycobacteriosis and treatment regimens for TB and NTM are different, identifying the disease-causing species is paramount to indicate the correct management. Thus, in the laboratory routine, when an isolate presumptively classified as MTBC is MTBC-negative, it is still essential to perform subsequent identification.
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Infecciones por Mycobacterium no Tuberculosas , Tuberculosis Pulmonar , Tuberculosis , Humanos , Micobacterias no Tuberculosas , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/diagnóstico , Tuberculosis/microbiología , GenotipoRESUMEN
This study aimed to propose and evaluate a drug susceptibility testing (DST) using the 2,3,5-triphenyl tetrazolium chloride (TTC) as a colorimetric indicator against Mycobacterium abscessus complex (MABC), M. avium complex (MAC), and M. kansasii strains, main nontuberculous mycobacteria (NTM) of clinical relevance. Our results demonstrated that the assay using TTC and the broth microdilution method recommended by the Clinical and Laboratory Standards Institute had essential agreement above 91%, 92%, and 100%, for drugs tested against MABC, MAC, and M. kansasii strains, respectively. Categorical agreement above 91% was obtained for most drugs tested against MABC, except to cefoxitin (76.5%). For drugs tested against MAC and M. kansasii, categorical agreement above 92% and 100% was observed, respectively. TTC showed to be a promising colorimetric indicator of growth to be used in DST for NTM, allowing an easier reading of results.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Mycobacterium tuberculosis , Humanos , Micobacterias no Tuberculosas , Infecciones por Mycobacterium no Tuberculosas/microbiología , Antibacterianos/uso terapéutico , Cloruros , Colorimetría , Pruebas de Sensibilidad MicrobianaAsunto(s)
Infecciones por Mycobacterium no Tuberculosas , Humanos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/etiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Grasa Abdominal , Antibacterianos/uso terapéuticoAsunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Cuero Cabelludo , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/etiología , América Central , Cabello , Antibacterianos/uso terapéuticoRESUMEN
A female patient in her 30s presented to the emergency department with a 10-day history of fever, weakness and diaphoresis. Subsequent investigations revealed a diagnosis of haemophagocytic syndrome, secondary to disseminated non-tuberculous mycobacterial infection affecting the bone marrow, lungs, lymph nodes and skin. The bone marrow culture confirmed the presence of Mycobacterium avium infection. The patient's haemophagocytic syndrome was managed using the HLH-2004 chemoimmunotherapy, and M. avium infection was treated with a combination of clarithromycin, ethambutol, rifampicin, ciprofloxacin and amikacin. Throughout her hospitalisation, the patient faced several serious complications arising from both the medications and the prolonged hospital stay (lasting 12 months). However, these complications were promptly identified and effectively managed through a multidisciplinary and comprehensive approach. This approach was crucial in achieving a favourable patient outcome and successful recovery.
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Linfohistiocitosis Hemofagocítica , Infecciones por Mycobacterium no Tuberculosas , Infecciones Oportunistas , Femenino , Humanos , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Amicacina , CiprofloxacinaRESUMEN
Introducción: la micobacteria no terberculosa (NTM) forma un grupo heterogéneo de microorganismos que pueden causar infección en humanos. Las micobacterias no pigmentadas de rápido crecimiento (MNPCR) son de interés clínico debido al creciente número de pacientes infectados por ellos y a la dificultad del tratamiento. Dentro de este grupo, Mycobacterium fortuitum, Mycobacterium abscessus y Mycobacterium chelonae son reconocidos como patógenos potenciales; estas especies se han aislado de infecciones pulmonares y extrapulmonares. Objetivo: el objetivo de este trabajo es encontrar la frecuencia de aislamiento de especies micobacterianas de rápido crecimiento, específicamente el complejo Mycobacterium fortuitum, de muestras clínicas utilizando la técnica molecular de diagnóstico GenoType Mycobacterium CM. Material y Método: se analizaron 249 aislados de micobacterias no tuberculosas obtenidas de muestras pulmonares y extrapulmonares de pacientes sintomáticos en el período enero 2018-diciembre de 2022. La técnica molecular GenoType Mycobacterium CM se utilizó para identificar la especie. Resultados: Se obtuvieron 77 (3,9%) aislados de especies no pigmentadas de rápido crecimiento, estas se identificaron en orden decreciente: Mycobacterium fortuitum 65 (84,41%), Mycobacterium abcessus 9 (11,68%) y Mycobacterium chelonae 3 (4%). Conclusiones: los resultados reafirman que el complejo Mycobacterium fortuitum es responsable de la mayoría de las infecciones causadas por la micobacteria en rápido crecimiento en humanos. La técnica diagnóstica GenoType Mycobacterium CM es una herramienta útil para la rápida identificación de micobacterias; proporciona resultados precisos en menos tiempo, acortando significativamente el tiempo diagnóstico, permite la aplicación temprana de tratamiento específico, evitando así la propagación de la infección.
Introduction: non-tuberculous mycobacteria (NTM) form a heterogeneous group of mi-croorganisms that can cause infection in humans. Fast-growing non-pigmented my-cobacteria (MNPCR) are of clinical interest due to the increasing number of patients infected by them and the difficulty of treatment. Within this group, Mycobacterium fortuitum, Mycobacterium abscessus and Mycobacterium chelonae are recognized as potential pathogens; these species have been isolated from both pulmonary and ex-trapulmonary infections. Objective: the objective of this work is to find the frequency of isolation of fast-growing non-pigmented mycobacterial species, specifically the Myco-bacterium fortuitum complex, from clinical samples using the GenoType® Mycobacteri-um CM diagnostic molecular technique. Material and Method: 249 isolates of non-tu-berculous mycobacteria obtained from pulmonary and extrapulmonary samples from symptomatic patients in the period January 2018-December 2022 were analyzed. The G e n oTy p e® Mycobacterium CM molecular technique was used to identify the species. Results: 77 (30.9%) isolates of fast-growing non-pigmented species were obtained, these were identified in decreasing order: Mycobacterium fortuitum 65 (84.41%), Myco-bacterium abcessus 9 (11.68%) and Mycobacterium chelonae 3 (4%). Conclusions: the results reaffirm that the Mycobacterium fortuitum complex is responsible for most in-fections caused by fast-growing mycobacteria in humans. The GenoType® Mycobacte-riumCM diagnostic technique is a useful tool for the rapid identification of mycobacte-ria; it provides accurate results in less time, significantly shortening the diagnostic time, it allows the early application of specific treatment, thus avoiding the spread of infec-tion.
Asunto(s)
Humanos , Micobacterias no Tuberculosas/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Terapéutica , Técnicas de Diagnóstico Molecular/métodosRESUMEN
Drug repositioning is an alternative to overcome the complexity of the drug discovery and approval procedures for the treatment of Mycobacterium abscessus Complex (MABSC) infections that are increasing globally due to the emergency of antimicrobial resistance mechanisms. Here, an in silico chemogenomics approach was performed to compare the sequences from 4942 M. abscessus subsp. abscessus (M. abscessus) proteins with 5258 or 3473 therapeutic targets registered in the DrugBank or Therapeutic Target Database, respectively. This comparison identified 446 drugs or drug candidates whose targets were homologous to M. abscessus proteins. These identified drugs were considered potential inhibitors of MABSC (anti-MABSC activity). Further screening and inspection resulted in the selection of ezetimibe, furosemide, itraconazole, miconazole (MCZ), tamoxifen (TAM), and thiabendazole (THI) for experimental validation. Among them, MCZ and TAM showed minimum inhibitory concentrations (MIC) of 32 and 24 µg mL-1 against M. abscessus, respectively. For M. bolletii and M. massiliense strains, MCZ and TAM showed MICs of 16 and 24 µg mL-1, in this order. Subsequently, the antibacterial activity of MCZ was confirmed in vivo, indicating its potential to reduce the bacterial load in the lungs of infected mice. These results show that MCZ and TAM can serve as molecular scaffolds for the prospective hit-2-lead optimization of new analogs with greater potency, selectivity, and permeability.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Animales , Ratones , Mycobacterium abscessus/genética , Miconazol/farmacología , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico , Reposicionamiento de Medicamentos , Estudios Prospectivos , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Antibacterianos/farmacología , Pruebas de Sensibilidad MicrobianaAsunto(s)
Turismo Médico , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Absceso/tratamiento farmacológico , México , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Antibacterianos/uso terapéutico , Pruebas de Sensibilidad MicrobianaRESUMEN
The incidence and clinical characteristics of NTM diseases in Brazil remain relatively unknown. The present study describes the diagnosis of NTM isolates, the clinical presentation and treatment outcomes. We analyzed NTM isolates in patients of a tertiary hospital in the Southeast region of Brazil, from January 2008 to July 2019. The ATS/IDSA criteria for diagnosis and treatment of these patients was applied. Mycobacterium kansasii were identified in 13/113 (11.5%) patients. In 59/113 (52.2%) patients who met the ATS criteria for disease, 29/59 (49.1%) received treatment, and 22/29 (75.8%) were cured. The major species identified was M. kansasii. The most frequent symptoms among the treated patients were dyspnea and cough, and the proportion of cured patients was high.