BACKGROUND: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination. METHODS: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe. In stage 1, healthy MenACWY vaccine-naive or -experienced 10- to 25-year-olds were randomized 1:2 to receive MenABCWY and placebo or MenB-fHbp and MenACWY-CRM. Eligible participants were randomly selected to participate in stage 2, which was an open-label immunopersistence and booster extension. Immunogenicity was assessed through serum bactericidal antibody using human complement (hSBA) assays with serogroups A/C/W/Y (MenA/C/W/Y) and 4 primary serogroup B (MenB) test strains. Immunogenicity endpoints included hSBA seroprotection rates through 48 months after primary vaccination and 1 month after the booster. Safety endpoints included booster reactogenicity events and adverse events (AEs). RESULTS: Of 1379 eligible participants, 353 entered stage 2; 242 completed the 48-month blood draw after primary vaccination and 240 completed the booster vaccination phase. MenA/C/W/Y seroprotection rates remained high for 4 years following a 2-dose MenABCWY primary series (MenACWY-naive, 62.0 %-100.0 %; MenACWY-experienced, 98.7 %-100.0 %) and trended higher than those after a single MenACWY-CRM dose (MenACWY-naive, 38.1 %-95.2 %; MenACWY-experienced, 89.7 %-100.0 %). Corresponding seroprotection rates against MenB remained stable and generally higher than baseline (MenABCWY, 18.2 %-36.6 %; MenB-fHbp, 16.2 %-31.9 % across strains). Following a booster, seroprotection rates against all 5 serogroups were ≥ 93.8 % across groups. Most booster dose reactogenicity events were mild or moderate in severity, and AEs were infrequent. CONCLUSIONS: Immune responses remained high for MenA/C/W/Y and above baseline for MenB through 4 years after the MenABCWY primary series, with robust responses for all 5 serogroups observed following a booster. The MenABCWY booster had an acceptable safety and tolerability profile consistent with the primary series. NCT03135834.
- MeSH
- dítě MeSH
- dospělí MeSH
- imunogenicita vakcíny MeSH
- komplement imunologie MeSH
- lidé MeSH
- meningokokové infekce * prevence a kontrola imunologie MeSH
- meningokokové vakcíny * imunologie škodlivé účinky aplikace a dávkování MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Neisseria meningitidis imunologie MeSH
- protilátky bakteriální * krev MeSH
- sekundární imunizace * metody MeSH
- séroskupina MeSH
- vakcíny konjugované imunologie aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Evropa MeSH
- Spojené státy americké MeSH
To trace evolution of Panton-Valentine leucocidin-positive clonal complex 398 methicillin-resistant Staphylococcus aureus (MRSA) in the Czech Republic, we tested 103 MRSA isolates from humans. Five (4.9%) were Panton-Valentine leucocidin-positive clonal complex 398, sequence types 1232 and 9181. Spread to the Czech Republic may result from travel to or from other countries.
- MeSH
- bakteriální toxiny * biosyntéza genetika MeSH
- dějiny 21. století MeSH
- dospělí MeSH
- exotoxiny * genetika biosyntéza MeSH
- leukocidiny * genetika MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus * genetika izolace a purifikace MeSH
- stafylokokové infekce * mikrobiologie epidemiologie MeSH
- Check Tag
- dějiny 21. století MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Česká republika MeSH
Ravulizumab is a humanized monoclonal antibody targeting the complement C5 protein. This drug has been approved by different regulatory agencies worldwide for the treatment of AQP-4 seropositive NMOSD based on the results of the CHAMPION-NMOSD trial. Similar to eculizumab, ravulizumab offers highly effective prevention of NMOSD relapses. Both molecules demonstrated more than 90% reduction in relapse risk compared to the placebo group. Ravulizumab has a longer half-life allowing extending interval dosing from two to eight weeks compared to eculizumab. Patients taking C5 complement inhibitors have an increased risk of serious meningococcal infections, therefore vaccination is mandatory before treatment initiation.
- Klíčová slova
- studie CHAMPION-NMOSD, Ravulizumab, AQP4-IgG pozitivní NMOSD,
- MeSH
- akvaporin 4 antagonisté a inhibitory imunologie MeSH
- humanizované monoklonální protilátky * farmakologie klasifikace terapeutické užití MeSH
- klinická studie jako téma MeSH
- komplement C5 antagonisté a inhibitory MeSH
- lidé MeSH
- meningokokové infekce imunologie prevence a kontrola MeSH
- neuromyelitis optica * diagnóza farmakoterapie imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Wild strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were tested in an experimental hyperbaric chamber to determine the possible effect of hyperbaric oxygen on the susceptibility of these strains to the antibiotics ampicillin, ampicillin + sulbactam, cefazolin, cefuroxime, cefoxitin, gentamicin, sulfamethoxazole + trimethoprim, colistin, oxolinic acid, ofloxacin, tetracycline, and aztreonam during their cultivation at 23 °C and 36.5 °C. Ninety-six-well inoculated microplates with tested antibiotics in Mueller-Hinton broth were cultured under standard incubator conditions (normobaric normoxia) for 24 h or in an experimental hyperbaric chamber (HAUX, Germany) for 24 h at 2.8 ATA of 100% oxygen (hyperbaric hyperoxia). The hyperbaric chamber was pressurised with pure oxygen (100%). Both cultures (normoxic and hyperoxic) were carried out at 23 °C and 36.5 °C to study the possible effect of the cultivation temperature. No significant differences were observed between 23 and 36.5 °C cultivation with or without the 2-h lag phase in Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Cultivation in a hyperbaric chamber at 23 °C and 36.5 °C with or without a 2-h lag phase did not produce significant changes in the minimum inhibitory concentration (MIC) of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. For the tested strains of Pseudomonas aeruginosa, the possible effect of hyperbaric oxygen on their antibiotic sensitivity could not be detected because the growth of these bacteria was completely inhibited by 100% hyperbaric oxygen at 2.8 ATA under all hyperbaric conditions tested at 23 °C and 36.5 °C. Subsequent tests with wild strains of pseudomonads, burkholderias, and stenotrophomonads not only confirmed the fact that these bacteria stop growing under hyperbaric conditions at a pressure of 2.8 ATA of 100% oxygen but also indicated that inhibition of growth of these bacteria under hyperbaric conditions is reversible.
- MeSH
- ampicilin farmakologie MeSH
- anaerobní bakterie MeSH
- antibakteriální látky farmakologie MeSH
- Bacteria MeSH
- Escherichia coli MeSH
- hyperbarická oxygenace * MeSH
- Klebsiella pneumoniae MeSH
- kombinace léků trimethoprim a sulfamethoxazol farmakologie MeSH
- kyslík MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- oxidační stres MeSH
- pseudomonádové infekce * MeSH
- Pseudomonas aeruginosa MeSH
- sulbaktam MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Faecal microbiota transplantation (FMT) is the standard treatment for patients with multiple recurrent Clostridioides difficile infection (rCDI). Recently, new commercially developed human microbiota-derived medicinal products have been evaluated and Food and Drug Administration-approved with considerable differences in terms of composition, administration, and targeted populations. OBJECTIVES: To review available data on the different microbiota-derived treatments at the stage of advanced clinical evaluation and research in rCDI in comparison with FMT. SOURCES: Phase II or III trials evaluating a microbiota-derived medicinal product to prevent rCDI. CONTENT: Two commercial microbiota-derived medicinal products are approved by the Food and Drug Administration: Rebyota (RBX2660 Ferring Pharmaceuticals, marketed in the United States) and VOWST (SER-109 -Seres Therapeutics, marketed in the United States), whereas VE303 (Vedanta Biosciences Inc) will be studied in phase III trial. RBX2660 and SER-109 are based on the processing of stools from healthy donors, whereas VE303 consists of a defined bacterial consortium originating from human stools and produced from clonal cell banks. All have proven efficacy to prevent rCDI compared with placebo in patients considered at high risk of recurrence. However, the heterogeneity of the inclusion criteria, and the time between each episode and CDI diagnostics makes direct comparison between trials difficult. The differences regarding the risk of recurrence between the treatment and placebo arms were lower than previously described for FMT (FMT: Δ = 50.5%; RBX2660-phase III: Δ = 13.1%; SER-109-phase III: Δ = 28%; high-dose VE303-phase-II: Δ = 31.7%). All treatments presented a good overall safety profile with mainly mild gastrointestinal symptoms. IMPLICATIONS: Stool-derived products and bacterial consortia need to be clearly distinguished in terms of product characterization and their associated risks with specific long-term post-marketing evaluation similar to registries used for FMT. Their place in the therapeutic strategy for patients with rCDI requires further studies to determine the most appropriate patient population and administration route to prevent rCDI.
- MeSH
- Clostridioides difficile * MeSH
- fekální transplantace MeSH
- klostridiové infekce * mikrobiologie MeSH
- lidé MeSH
- mikrobiota * MeSH
- recidiva MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Tick-borne encephalitis (TBE) and Lyme neuroborreliosis (LNB), the most common tick-borne diseases of the central nervous system in Central Europe, are frequently associated with pareses. The aim of this study was to characterise paretic complications in patients with TBE and LNB, including their severity, persistence and impact on the patients' quality of life. Our retrospective observational study included patients with aseptic CNS infection due to TBE virus or Borrelia burgdorferi sensu lato. Paretic complications were evaluated in the acute phase and the patients were followed up until complete regression or long-term stabilisation of any neurological deficit. The severity of the neurological deficit was graded according to the modified Rankin Scale (mRS). A total of 823 patients (582 with TBE, 241 with LNB) was included. Paretic complications were diagnosed in 63 TBE patients (10.8 %) and in 147 LNB patients (61.0 %). In TBE, the most common neurological deficit was brachial plexus paresis in 21 patients (33 %) and bulbar symptoms in 18 patients (29 %). In LNB patients, facial nerve palsy was the most frequent neurological deficit (117patients; 79.6 %), followed by lower limb paresis in 23 patients (15.6 %). Forty-nine TBE patients and 134 LNB paretic patients completed follow-up. Paresis resolved within 3 weeks in 16 TBE patients (33 %) and 53 LNB patients (39.5 %), but the proportion of patients with paresis persisting for more than 12 months was significantly higher in TBE (34.7 vs. 3.7 %, p < 0.001). The mean mRS was significantly higher in TBE paretic patients compared to LNB (p < 0.001). Paretic complications are significantly more common in LNB than in TBE but pareses associated with TBE last longer than in LNB and considerably reduce the quality of life of patients. Prevention remains the only way to influence the long-term motor deficits of TBE.
- MeSH
- klíšťová encefalitida * komplikace epidemiologie diagnóza MeSH
- kvalita života MeSH
- lidé MeSH
- lymská neuroborelióza * komplikace epidemiologie diagnóza MeSH
- paréza etiologie komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. OBJECTIVE: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). DESIGN: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. RESULTS: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. CONCLUSION: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. TRIAL REGISTRATION NUMBER: NCT02328131.
- MeSH
- amoxicilin terapeutické užití aplikace a dávkování MeSH
- antibakteriální látky * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- bismut * terapeutické užití aplikace a dávkování MeSH
- dospělí MeSH
- Helicobacter pylori * účinky léků MeSH
- infekce vyvolané Helicobacter pylori * farmakoterapie MeSH
- inhibitory protonové pumpy * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- klarithromycin terapeutické užití aplikace a dávkování MeSH
- kombinovaná farmakoterapie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- metronidazol terapeutické užití aplikace a dávkování MeSH
- registrace * MeSH
- senioři MeSH
- tetracyklin terapeutické užití aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Evropa 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
- dospělí MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- molekulární epidemiologie * MeSH
- multirezistentní tuberkulóza epidemiologie MeSH
- Mycobacterium tuberculosis * genetika izolace a purifikace MeSH
- osoby s přechodným pobytem a migranti * statistika a číselné údaje MeSH
- ozbrojené konflikty MeSH
- prospektivní studie MeSH
- tuberkulóza * epidemiologie přenos MeSH
- uprchlíci * statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
- Ukrajina MeSH
Brucellosis is a zoonosis caused by Brucella, which poses a great threat to human health and animal husbandry. Pathogen surveillance is an important measure to prevent brucellosis, but the traditional method is time-consuming and not suitable for field applications. In this study, a recombinase polymerase amplification-SYBR Green I (RPAS) assay was developed for the rapid and visualized detection of Brucella in the field by targeting BCSP31 gene, a conserved marker. The method was highly specific without any cross-reactivity with other common bacteria and its detection limit was 2.14 × 104 CFU/mL or g of Brucella at 40 °C for 20 min. It obviates the need for costly instrumentation and exhibits robustness towards background interference in serum, meat, and milk samples. In summary, the RPAS assay is a rapid, visually intuitive, and user-friendly detection that is highly suitable for use in resource-limited settings. Its simplicity and ease of use enable swift on-site detection of Brucella, thereby facilitating timely implementation of preventive measures.
- MeSH
- Brucella * genetika izolace a purifikace MeSH
- brucelóza * diagnóza mikrobiologie MeSH
- DNA bakterií genetika MeSH
- lidé MeSH
- limita detekce MeSH
- mléko mikrobiologie MeSH
- rekombinasy * metabolismus genetika MeSH
- senzitivita a specificita MeSH
- skot MeSH
- techniky amplifikace nukleových kyselin * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Complex injuries to the posterior trunk can still pose a significant challenge to the reconstructive surgeon. Due to the lack of skin laxity, dependent anatomical location and the importance of the deeper structures, a systematic approach tailored to the individual defect should be considered for these types of reconstructions. In our case report, we present a reconstructive solution of a chronic defect of the back caused by resection of an ulceration. What was previously considered to be a relapse of a malignant melanoma turned out to be a chronic osteomyelitis of the spinous processes of the thoracic vertebrae. The defect after the resection of the ulceration and infected spinous processes of the thoracic vertebrae with exposed dorsal lamina was covered with pedicled myocutaneous flap. Reconstruction yielded well-vascularized tissue that provided sufficient volume and tissue quality. Even in the light of modern perforator flaps, local or locoregional muscle and myocutaneous flaps remain the first choice for the treatment of deep back defects. Considering all the factors in the given case, plastic surgeons are able to tailor the reconstructive technique to every individual case to match the desired reconstruction goal.
- MeSH
- chirurgické laloky * chirurgie MeSH
- dermatochirurgické výkony metody MeSH
- hrudní obratle chirurgie patologie MeSH
- lidé MeSH
- maligní melanom kůže komplikace MeSH
- osteomyelitida * chirurgie MeSH
- pooperační péče metody MeSH
- senioři MeSH
- stafylokokové infekce komplikace MeSH
- vřed chirurgie komplikace patologie MeSH
- záda chirurgie patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH