BackgroundOn 29 January 2024, the European Centre for Disease Prevention and Control distributed an alert about a metronidazole-resistant Clostridioides difficile outbreak of PCR ribotype (RT) 955 in England.AimWe aimed to investigate the presence of RT955 in Czech, Slovak and Polish C. difficile isolates and evaluate different culture media for detecting its metronidazole resistance.MethodsIsolates with binary toxin genes identified as 'unknown' by the WEBRIBO PCR ribotyping database up to 2023 were re-analysed after adding the RT955 profile to the database. The RT955 isolates were characterised by whole genome sequencing and tested for susceptibility to 15 antimicrobials.ResultsWe did not find RT955 in Czech (n = 6,661, 2012-2023) and Slovak (n = 776, 2015-2023) isolates, but identified 13 RT955 cases (n = 303, 2021-2023) in three hospitals in Poland. By whole genome multilocus sequence typing, 10 isolates clustered into one clonal complex including a sequence of United Kingdom strain ERR12670107, and shared similar antimicrobial resistance genes/mutations. All 13 isolates were resistant to ciprofloxacin/moxifloxacin, erythromycin/clindamycin and ceftazidime. All isolates had a mutation in the nimB gene promoter and in NimB (Tyr130Ser and Leu155Ile). The metronidazole resistance was detected in all isolates using brain-heart-infusion agar supplemented with haemin and Chocolate agar. Results were discrepant with the European Committee on Antimicrobial Susceptibility Testing-recommended Fastidious anaerobe agar and Brucella blood agar.ConclusionThe identification of clonally related haem-dependent metronidazole-resistant C. difficile RT955 in multiple hospitals indicates a need for prospective surveillance to estimate its prevalence in Europe.
- MeSH
- antibakteriální látky * farmakologie MeSH
- bakteriální léková rezistence * genetika MeSH
- Clostridioides difficile * genetika účinky léků izolace a purifikace klasifikace MeSH
- epidemický výskyt choroby MeSH
- klostridiové infekce * epidemiologie mikrobiologie farmakoterapie MeSH
- lidé MeSH
- metronidazol * farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- multilokusová sekvenční typizace MeSH
- polymerázová řetězová reakce MeSH
- ribotypizace * MeSH
- sekvenování celého genomu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Polsko MeSH
- Slovenská 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
During hypoxia, tissues are subjected to an inadequate oxygen supply, disrupting the balance needed to maintain normal function. This deficiency can occur due to reduced oxygen delivery caused by impaired blood flow or a decline in the blood's ability to carry oxygen. In tumors, hypoxia and vascularization play crucial roles, shaping their microenvironments and influencing cancer progression, response to treatment and metastatic potential. This chapter provides guidance on the use of non-invasive imaging methods including Positron Emission Tomography and Magnetic Resonance Imaging to study tumor oxygenation in pre-clinical settings. These imaging techniques offer valuable insights into tumor vascularity and oxygen levels, aiding in understanding tumor behavior and treatment effects. For example, PET imaging uses tracers such as [18F]-fluoromisonidazole (FMISO) to visualize hypoxic areas within tumors, while MRI complements this with anatomical and functional images. Although directly assessing tumor hypoxia with MRI remains challenging, techniques like Blood Oxygen Level Dependent (BOLD) and Dynamic Contrast-Enhanced MRI (DCE-MRI) provide valuable information. BOLD can track changes in oxygen levels during oxygen challenges, while DCE-MRI offers real-time access to perfusion and vessel permeability data. Integrating data from these imaging modalities can help assess oxygen supply, refine treatment strategies, enhance therapeutic effectiveness, and ultimately improve patient outcomes.
- MeSH
- hypoxie diagnostické zobrazování MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- misonidazol analogy a deriváty MeSH
- myši MeSH
- nádorová hypoxie MeSH
- nádory diagnostické zobrazování krevní zásobení patologie MeSH
- patologická angiogeneze diagnostické zobrazování patologie MeSH
- pozitronová emisní tomografie * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Trichomoniasis, a globally distributed sexually transmitted infection, is caused by the urogenital parasite Trichomonas vaginalis Donné, 1836 affecting both women and men. The treatment of choice is metronidazole (MTZ). In the present study, 15 samples of vaginal discharge and urine were analysed by sequencing nitroreductase genes (ntr4 and ntr6). An in silico model was structured to illustrate the location of point mutations (PM) in the protein. The ntr4 gene presented four PMs: G76C (10/10), C213G (9/10), C318A (5/10) and G424A (1/10), while the ntr6 gene had eight PMs; G593A (13/13) the most frequent, G72T and G627C, both in 8/13. The PM C213G and A438T generated a stop codon causing a truncated nitroreductase 4 and 6 protein. Docking analysis demonstrated that some models had a decrease in binding affinity to MTZ (p < 0.0001). A high frequency of mutations was observed in the samples analysed that could be associated with resistance to MTZ in Chile.
- MeSH
- antiprotozoální látky farmakologie MeSH
- bodová mutace * MeSH
- léková rezistence * MeSH
- lidé MeSH
- metronidazol * farmakologie MeSH
- nitroreduktasy * genetika metabolismus MeSH
- protozoální proteiny genetika metabolismus MeSH
- trichomonádová vaginitida parazitologie MeSH
- Trichomonas vaginalis * genetika účinky léků enzymologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Chile MeSH
- MeSH
- amébová dyzenterie diagnóza farmakoterapie komplikace MeSH
- ceftriaxon aplikace a dávkování terapeutické užití MeSH
- dítě MeSH
- Entamoeba histolytica MeSH
- epiglotitida diagnóza terapie MeSH
- infekční nemoci * diagnóza epidemiologie farmakoterapie MeSH
- lidé MeSH
- metronidazol aplikace a dávkování terapeutické užití MeSH
- praziquantel aplikace a dávkování terapeutické užití MeSH
- Schistosoma MeSH
- schistosomiasis mansoni diagnóza epidemiologie farmakoterapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Geografické názvy
- Keňa MeSH
Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .
- MeSH
- antibakteriální látky terapeutické užití aplikace a dávkování MeSH
- dospělí MeSH
- Helicobacter pylori * účinky léků MeSH
- infekce vyvolané Helicobacter pylori * farmakoterapie epidemiologie mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metronidazol terapeutické užití aplikace a dávkování MeSH
- nádory žaludku * prevence a kontrola epidemiologie mikrobiologie MeSH
- omeprazol * terapeutické užití aplikace a dávkování MeSH
- organokovové sloučeniny terapeutické užití aplikace a dávkování MeSH
- senioři MeSH
- tetracyklin terapeutické užití aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Čína MeSH
Echinokokóza je vzácné parazitární onemocnění, které postihuje vícero orgánů. V některých případech může imitovat generalizované onkologické onemocnění jako v případě našeho pacienta. V článku se také snažíme upozornit na nutnost správné diagnostiky a následné okamžité léčebné intervence.
Echinococcosis is a rare parasitic disease that affects multiple organs. In some cases, it can imitate a generalized oncological disease, as in the case of our patient. In these article, we also point out to the necessity of correct diagnosis and immediate adequate treatment intervention.
- MeSH
- cefotaxim terapeutické užití MeSH
- dospělí MeSH
- echinokokóza jater diagnóza terapie MeSH
- echinokokóza * diagnóza parazitologie terapie MeSH
- lidé MeSH
- metronidazol terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
IMPORTANCE: Bacterial vaginosis (BV) is a common cause of vaginal infection. First-line treatments of BV are metronidazole and clindamycin. Due to the increase in antibiotic resistance, effective nonantibiotic treatments for BV are needed. OBJECTIVE: To examine whether dequalinium chloride, a broad-spectrum antiseptic, is noninferior to oral metronidazole for the treatment of BV. DESIGN, SETTING, AND PARTICIPANTS: This phase 4, multicenter, triple-blind, double-dummy, parallel, noninferiority randomized clinical trial was conducted from July 29, 2021, to August 25, 2022, with a 1-month follow-up. Participants were premenopausal women 18 years or older with BV from 11 gynecologic practices and 1 hospital in Poland, Slovakia, and the Czech. INTERVENTION: Patients were randomized to treatment with dequalinium chloride vaginal tablets (10 mg once daily for 6 days) or oral metronidazole (500 mg twice daily for 7 days). Double-dummy medication kits contained vaginal and oral tablets with placebo and active medication. MAIN OUTCOMES AND MEASURES: The main outcome was the noninferiority margin (of 15 percentage points) in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after start of treatment (visit 1). Noninferiority was met if the lower 95% CI for the difference in clinical cure rate was less than 15 percentage points at visit 1. RESULTS: A total of 147 women (mean [SD] age, 36.7 [9.0] years) were treated with dequalinium chloride (n = 72) or metronidazole (n = 75). The clinical cure rates at visit 1 were 64 of 69 (92.8%) for dequalinium chloride vs 69 of 74 (93.2%) for metronidazole in the intention-to-treat population, whereas in the per-protocol population, cure rates were 54 of 58 (93.1%) for dequalinium chloride vs 48 of 53 (90.6%) for metronidazole. The treatment differences of -0.5 percentage points (95% CI, -10.8 to 9.8 percentage points; P = .002) in the intention-to-treat population and 2.5 percentage points (95% CI, -9.4 to 14.4 percentage points; P = .001) in the per-protocol population confirmed the noninferiority of dequalinium chloride. The tolerability of dequalinium chloride was rated as very good by 30 of 50 patients (60.0%) but only by 21 of 54 (38.9%) for metronidazole. Three patients in the metronidazole group suspended treatment due to an adverse event. CONCLUSIONS AND RELEVANCE: This randomized clinical trial showed that dequalinium chloride was not inferior to metronidazole for the treatment of BV. Dequalinium chloride had a similarly high cure rate but with better tolerability and fewer adverse events. With a similar efficacy to metronidazole and clindamycin, dequalinium chloride warrants consideration as first-line treatment for BV to help reduce antibiotic consumption. TRIAL REGISTRATION: EudraCT: 2020-002489-15.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- aplikace intravaginální MeSH
- aplikace orální MeSH
- bakteriální vaginóza * farmakoterapie MeSH
- dechalinium * terapeutické užití MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- metronidazol * terapeutické užití MeSH
- mladý dospělý MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze IV MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.
- MeSH
- adherence k farmakoterapii * statistika a číselné údaje MeSH
- amoxicilin * terapeutické užití aplikace a dávkování MeSH
- antibakteriální látky * terapeutické užití škodlivé účinky MeSH
- bismut terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- dospělí MeSH
- dyspepsie farmakoterapie mikrobiologie MeSH
- Helicobacter pylori * účinky léků MeSH
- infekce vyvolané Helicobacter pylori * farmakoterapie MeSH
- inhibitory protonové pumpy * terapeutické užití aplikace a dávkování MeSH
- klarithromycin terapeutické užití MeSH
- kombinovaná farmakoterapie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- metronidazol terapeutické užití aplikace a dávkování MeSH
- prospektivní studie MeSH
- registrace * MeSH
- senioři 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
- Geografické názvy
- Evropa MeSH
Pevná bismutová kapková elektroda (SBiDE – solid bismuth drop electrode) je nová pracovní elektroda, kterou od roku 2020 komerčně nabízí na českém trhu společnost Metrohm. Cílem této práce bylo ověřit použitelnost SBiDE při voltametrickém stanovení modelové organické látky reprezentující elektrochemicky redukovatelné biologicky aktivní sloučeniny – léčiva metronidazolu (antibiotika používaného k léčbě onemocnění způsobených gram-pozitivními i gram-negativními anaerobními bakteriemi). Podle dostupných informací se jedná o vůbec první publikovanou výzkumnou práci využívající SBiDE. Za optimálních podmínek (Brittonův-Robinsonův pufr o pH 12,0 byl použitý jako základní elektrolyt a povrch pracovní elektrody nebyl elektrochemicky regenerován) byla získána pomocí diferenční pulzní voltametrie (DPV) lineární kalibrační závislost metronidazolu v koncentračním rozmezí od 1 do 600 μmol l−1, přičemž dosažená mez detekce (LOD) byla 0,41 μmol l−1 a mez stanovitelnosti (LOQ) byla 1,4 μmol l−1. Cyklická voltametrie (CV) na SBiDE byla použita pro charakterizaci elektrodového děje při ireverzibilní katodické redukci metronidazolu. Nově vyvinutá DPV metoda byla rovněž úspěšně použita při stanovení metronidazolu v autentických vzorcích pitné vody (LOD = 1,8 μmol l−1 a LOQ = 5,8 μmol l−1) a v různých lékových formách (jako srovnávací analytická metoda byla použita UV-Vis spektrofotometrie).
Solid bismuth drop electrode (SBiDE) is a new working electrode commercially available on the Czech market since 2020 by the company Metrohm. The aim of this work was to verify the applicability of SBiDE for the voltammetric determination of a model organic substance representing electrochemically reducible biologically active compounds, namely, the drug metronidazole (an antibiotic used to treat diseases caused by both Gram-positive and Gram-negative anaerobic bacteria). To the best of our knowledge, this is the very first published research work using SBiDE. Under optimum conditions (Britton-Robinson buffer of pH 12.0 was used as the supporting electrolyte and the working electrode surface was not electrochemically regenerated), a linear calibration dependence of metronidazole was obtained using differential pulse voltammetry (DPV) in the concentration range from 1 to 600 μmol L–1, with the limits of detection (LOD) and quantification (LOQ) of 0.41 μmol L–1 and 1.4 μmol L–1, respectively. Cyclic voltammetry (CV) on SBiDE was used to characterize the electrode process of the irreversible reduction of metronidazole. The newly developed DPV method was also successfully applied for the determination of metronidazole in authentic drinking water samples (LOD = 1.8 μmol L−1 and LOQ = 5.8 μmol L−1) and in various dosage forms (UV-Vis spectrophotometry was used as a comparative analytical method).
