3,5-Dinitrobenzylsulfanyl tetrazoles and 1,3,4-oxadiazoles, previously identified as having high in vitro activities against both replicating and nonreplicating mycobacteria and favorable cytotoxicity and genotoxicity profiles were investigated. First we demonstrated that these compounds act in a deazaflavin-dependent nitroreduction pathway and thus require a nitro group for their activity. Second, we confirmed the necessity of both nitro groups for antimycobacterial activity through extensive structure-activity relationship studies using 32 structural types of analogues, each in a five-membered series. Only the analogues with shifted nitro groups, namely, 2,5-dinitrobenzylsulfanyl oxadiazoles and tetrazoles, maintained high antimycobacterial activity but in this case mainly as a result of DprE1 inhibition. However, these analogues also showed increased toxicity to the mammalian cell line. Thus, both nitro groups in 3,5-dinitrobenzylsulfanyl-containing antimycobacterial agents remain essential for their high efficacy, and further efforts should be directed at finding ways to address the possible toxicity and solubility issues, for example, by targeted delivery.

• MeSH
• Antitubercular Agents pharmacology   chemistry   MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium tuberculosis * MeSH
• Nitroreductases MeSH
• Oxadiazoles pharmacology   chemistry   MeSH
• Mammals MeSH
• Tetrazoles pharmacology   chemistry   MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: The war in Ukraine has led to significant migration to neighboring countries, raising public health concerns. Notable tuberculosis (TB) incidence rates in Ukraine emphasize the immediate requirement to prioritize approaches that interrupt the spread and prevent new infections. METHODS: We conducted a prospective genomic surveillance study to assess migration's impact on TB epidemiology in the Czech Republic and Slovakia. Mycobacterium tuberculosis isolates from Ukrainian war refugees and migrants, collected from September 2021 to December 2022 were analyzed alongside 1574 isolates obtained from Ukraine, the Czech Republic, and Slovakia. RESULTS: Our study revealed alarming results, with historically the highest number of Ukrainian tuberculosis patients detected in the host countries. The increasing number of cases of multidrug-resistant TB, significantly linked with Beijing lineage 2.2.1 (p < 0.0001), also presents substantial obstacles to control endeavors. The genomic analysis identified the three highly related genomic clusters, indicating the recent TB transmission among migrant populations. The largest clusters comprised war refugees diagnosed in the Czech Republic, TB patients from various regions of Ukraine, and incarcerated individuals diagnosed with pulmonary TB specialized facility in the Kharkiv region, Ukraine, pointing to a national transmission sequence that has persisted for over 14 years. CONCLUSIONS: The data showed that most infections were likely the result of reactivation of latent disease or exposure to TB before migration rather than recent transmission occurring within the host country. However, close monitoring, appropriate treatment, careful surveillance, and social support are crucial in mitigating future risks, though there is currently no evidence of local transmission in EU countries.

• MeSH
• Adult MeSH
• Incidence MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Molecular Epidemiology * MeSH
• Tuberculosis, Multidrug-Resistant epidemiology   MeSH
• Mycobacterium tuberculosis * genetics   isolation & purification   MeSH
• Transients and Migrants * statistics & numerical data   MeSH
• Armed Conflicts MeSH
• Prospective Studies MeSH
• Tuberculosis * epidemiology   transmission   MeSH
• Refugees * statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Slovakia MeSH
• Ukraine MeSH

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.

• MeSH
• Mycobacterium Infections, Nontuberculous * microbiology   MeSH
• Phylogeny * MeSH
• Genome, Bacterial * MeSH
• Genomics * MeSH
• Humans MeSH
• Mycobacterium kansasii * genetics   classification   isolation & purification   MeSH
• Virulence genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION AND PURPOSE: Mycobacterium (M.) chelonae is responsible for a half of relatively rare nontuberculous mycobacteria (NTM) keratitis. We report a case of M. chelonae keratitis in a woman following sclerocorneal suture extraction after cataract surgery. RESULTS: A 70-year-old woman presented with a red eye and corneal infiltration of her left eye six weeks following sclerocorneal suture extraction after an elective cataract surgery in another institute. She complained of a sharp, cutting pain and photophobia. Since initial corneal scrapes and conjunctival swabs proved no pathogen using culture and PCR methods, non-specific antibiotics and antifungal agents were administered. As keratitis was complicated by an inflammation in the anterior chamber and vitreous, samples of the vitreous fluid were sent for microbiologic examination. DNA of Epstein-Barr virus (EBV) was repeatedly detected. Since the intrastromal abscess had formed, corneal re-scrapings were performed and M. chelonae was detected using culture, MALDI-TOF MS and PCR methods. Therapy was changed to a combination of oral and topical clarithromycin, intravitreal, topical and intracameral amikacin, and oral and topical moxifloxacin. The successful therapy led to stabilization. The optical penetrating keratoplasty was performed and no signs of the infection recurrence were found. CONCLUSIONS: The diagnosis of nontuberculous mycobacterial keratitis is difficult and often delayed. An aggressive and prolonged antimicrobial therapy should include systemic and topical antibiotics. Surgical intervention in the form of corneal transplantation may be required in the active and nonresponsive infection. In the presented case this was necessary for visual rehabilitation due to scarring.

• MeSH
• Amikacin therapeutic use   MeSH
• Anti-Bacterial Agents * therapeutic use   MeSH
• Mycobacterium Infections, Nontuberculous * diagnosis   drug therapy   microbiology   surgery   MeSH
• Fluoroquinolones therapeutic use   MeSH
• Keratitis * diagnosis   drug therapy   microbiology   surgery   MeSH
• Clarithromycin therapeutic use   MeSH
• Humans MeSH
• Moxifloxacin * therapeutic use   MeSH
• Mycobacterium chelonae * isolation & purification   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Review MeSH
• Geographicals
• Europe MeSH

Nová doporučení navazují na Standard léčebného plánu z roku 2012(1) a na vydání speciálního čísla Česko-slovenské pediatrie z roku 2016 věnovaného problematice tuberkulózy (TB).(2) V předkládaném dokumentu reflektujeme nová doporučení Světové zdravotnické organizace (WHO),(3) která dlouhodobě hledá nové strategie pro optimální léčbu dětských a dorostových pacientů, neboť celosvětově onemocní TB ročně více než 10 milionů lidí, z toho 1,2 milionu dětí.(4) V České republice zůstává TB vzácným onemocněním s incidencí 3,6 : 100 000 v roce 2022.(5) Dětská TB odráží trend dospělé TB. Mezi roky 2010–2020 byl trend klesající. Ani změna očkovací strategie v roce 2010 tento trend nezměnila.(6) Od roku 2021 pozorujeme mírný nárůst dětských pacientů s TB. V roce 2023 onemocnělo TB 29 dětí (obr. 1). Nárůst dětských případů TB, včetně forem rezistentních na léčbu, zvyšuje nárok na aktualizaci doporučení pro diagnostiku a léčbu v souladu se světovými trendy. Hlavní změny v doporučeném postupu se týkají zejména zkrácení léčby nekomplikované TB u dětí ve věku 3–16 let na 4 měsíce. Dále jsou zde nově definované skupiny TB rezistentní na léčbu (drug resistant – DR) a nové strategie její léčby, jejíž součástí je podávání bedaquilinu a delamanidu. Inovativní je také zavedení TB preventivní terapie u kontaktů s DR-TB.

The new recommendations are a follow-up to the 2012 Standard treatment guidelines(1) and the 2016 special issue of Czech-Slovak Paediatrics dedicated to tuberculosis (TB).(2) The present document reflects the new recommendations(3) of the World Health Organization (WHO), which has long been seeking new strategies for optimal treatment of paediatric and adolescent patients, as more than 10 million people worldwide develop TB annually, including 1.2 million children.(4) In the Czech Republic, TB remains a rare disease, with an incidence of 3.6/100,000 in 2022.(5) Childhood TB mirrors the trend of adult TB. Between 2010–2020, the trend was downward. Even the change in vaccination strategy in 2010 did not change this trend.(6) From 2021, we observe a slight increase in paediatric TB cases. In 2023, 29 children developed TB (Figure 1). The increase in paediatric TB cases, including treatment-resistant forms, makes it imperative to update recommendations for diagnosis and treatment in line with global trends. In particular, the main changes to the recommended approach relate to shortening treatment of uncomplicated TB in children aged 3-16 years to 4 months. There are also newly defined groups of drug-resistant (DR) TB and a new strategy for their treatment, which includes the administration of bedaquiline and delamanid. The introduction of TB preventive therapy for contacts of DR-TB is also innovative.

• MeSH
• Antitubercular Agents therapeutic use   MeSH
• BCG Vaccine MeSH
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Tuberculosis, Multidrug-Resistant classification   therapy   MeSH
• Mycobacterium tuberculosis immunology   isolation & purification   pathogenicity   MeSH
• Tuberculosis * diagnosis   prevention & control   therapy   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Practice Guideline MeSH
• Geographicals
• Czech Republic MeSH

Radiolabelled puromycin analogues will allow the quantification of protein synthesis through nuclear medicine-based imaging. A particularly useful application could be the non-invasive longitudinal visualisation of mycobacterial activity through direct quantification of puromycin binding. This study assesses the value of [68Ga]Ga-DOTA-puromycin in the visualisation of mycobacteria through positron emission tomography combined with magnetic resonance imaging (μPET/MRI). The radiopharmaceutical was produced by previously published and validated methods. [68Ga]Ga-DOTA-Puromycin imaging was performed on severe immunodeficient mice infected with Bacille Calmette-Guérin-derived M. Bovis (BCG). Acute and chronic infection stages were examined by μPET/MRI. A follow-up group of animals acted as controls (animals bearing S. aureus-derived infection and sterile inflammation) to assess tracer selectivity. [68Ga]Ga-DOTA-puromycin-μPET/MRI images revealed the acute, widespread infection within the right upper shoulder and armpit. Also, [68Ga]Ga-DOTA-puromycin signal sensitivity measured after a 12-week period was lower than that of [18F]FDG-PET in the same animals. A suitable correlation between normalised uptake values (NUV) and gold standard histopathological analysis confirms accurate tracer accumulation in viable bacteria. The radiopharmaceutical showed infection selectivity over inflammation but accumulated in both M. Bovis and S. Aureus, lacking pathogen specificity. Overall, [68Ga]Ga-DOTA-puromycin exhibits potential as a tool for non-invasive protein synthesis visualization, albeit without pathogen selectivity.

• MeSH
• Heterocyclic Compounds, 1-Ring chemistry   MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Mycobacterium bovis * MeSH
• Mycobacterium Infections diagnostic imaging   microbiology   MeSH
• Mice, SCID MeSH
• Mice MeSH
• Organometallic Compounds MeSH
• Positron-Emission Tomography * methods   MeSH
• Radiopharmaceuticals * chemistry   MeSH
• Gallium Radioisotopes * MeSH
• Tuberculosis diagnostic imaging   microbiology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

As an important source of human food, milk can be a carrier of human pathogenic bacteria, including tuberculous and nontuberculous mycobacteria (NTM), in its raw and unpasteurized state. In this research, 175 raw milk samples and 175 traditional cheese samples were collected from traditional dairy stores in 22 regions of Tehran in a 9- month period from August 2019 to May 2020. Samples were prepared and transferred to a specialized laboratory, where they were inoculated in Lowenstein-Jensen (LJ) medium containing glycerol or sodium pyruvate, as well as Herrold's egg-yolk with and without Mycobactin J. to determine the sample's identity of samples. The recommended 16S rRNA (1436 bp) and hsp65 (644 bp) gene fragments from the positive isolates identified in Ziehl-Neelsen (Z-N) staining were amplified and sequenced using PCR and compared with the sequences of the gene fragments of reference strains available in the global GenBank database. No mycobacterial species were isolated from traditional cheese samples in microbial culture. In case of raw milk samples, a total of four bacteria were collected, all of which were found in the genetic differential testing to be NTM, including n = 1 Mycobacterium heraklionense, n = 2 Mycolicibacterium fortuitum, and n = 1 Mycobacterium thermoresistibile. The analysis of the results obtained by isolate sequencing using the 16S rRNA gene showed higher discriminatory power and percentage similarities in the identification of the isolates than the hsp65 gene.

• MeSH
• Mycobacterium Infections, Nontuberculous * microbiology   MeSH
• Humans MeSH
• Milk microbiology   MeSH
• Nontuberculous Mycobacteria genetics   MeSH
• RNA, Ribosomal, 16S genetics   MeSH
• Cheese * microbiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Iran MeSH

• MeSH
• Anti-Bacterial Agents administration & dosage   MeSH
• Antibiotics, Antitubercular administration & dosage   adverse effects   therapeutic use   MeSH
• Humans MeSH
• Mycobacterium Infections * diagnosis   drug therapy   classification   MeSH
• Nontuberculous Mycobacteria * classification   pathogenicity   MeSH
• Mandatory Reporting MeSH
• Lung Diseases diagnosis   etiology   drug therapy   MeSH
• Tertiary Prevention MeSH
• Check Tag
• Humans MeSH

Tuberkulózni pacienti vyžadujúci akútnu intenzívnu starostlivosť tvoria asi 1–3 % zo všetkých pacientov s tuberkulózou. Respiračné zlyhanie bola najčastejšia príčina príjmu pacientov na intenzívne oddelenie v našej retrospektívnej analýze súboru pacientov (n = 36). Vstupná leukocytóza, hypoalbuminémia a SOFA skóre predstavujú významné prediktívne faktory určujúce prežívanie pacientov. Protektívna ventilačná stratégia pacientov s nehomogénnym pľúcnym parenchýmom pri rozvinutej infekcii tuberkulózy je podobná ako pri manažmente ARDS. Cielená terapia býva častokrát oneskorená pre netypický priebeh tuberkulózneho ochorenia a jeho foriem. Intravenózna antituberkulózna terapia na intenzívnej jednotke vykazuje lepšie prežívanie pacientov. Svetovo narastajúci počet pacientov s multirezistentnou tuberkulózou (MDR-TB) a extenzívne rezistentnou tuberkulózou (XDR-TB) predstavuje zvýšené riziko aj pre nemocničný personál.

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• MeSH
• Antitubercular Agents therapeutic use   MeSH
• Hypoalbuminemia blood   MeSH
• Leukocytosis blood   MeSH
• Humans MeSH
• Mycobacterium tuberculosis pathogenicity   MeSH
• Critical Care * MeSH
• Infectious Disease Transmission, Patient-to-Professional prevention & control   MeSH
• Respiratory Insufficiency etiology   therapy   MeSH
• Tuberculosis * diagnosis   drug therapy   microbiology   mortality   MeSH
• Organ Dysfunction Scores MeSH
• Check Tag
• Humans MeSH

• MeSH
• Antitubercular Agents * therapeutic use   pharmacology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests * MeSH
• Tuberculosis, Multidrug-Resistant * drug therapy   diagnosis   microbiology   MeSH
• Mycobacterium tuberculosis drug effects   genetics   MeSH
• Rifampin * therapeutic use   pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Comment MeSH
• Geographicals
• Europe MeSH