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
- Amoxicillin therapeutic use administration & dosage MeSH
- Anti-Bacterial Agents * therapeutic use adverse effects administration & dosage MeSH
- Bismuth * therapeutic use administration & dosage MeSH
- Adult MeSH
- Helicobacter pylori * drug effects MeSH
- Helicobacter Infections * drug therapy MeSH
- Proton Pump Inhibitors * therapeutic use administration & dosage adverse effects MeSH
- Clarithromycin therapeutic use administration & dosage MeSH
- Drug Therapy, Combination * MeSH
- Middle Aged MeSH
- Humans MeSH
- Metronidazole therapeutic use administration & dosage MeSH
- Registries * MeSH
- Aged MeSH
- Tetracycline therapeutic use administration & dosage MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Geographicals
- Europe 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
- Antiprotozoal Agents pharmacology MeSH
- Point Mutation * MeSH
- Drug Resistance * MeSH
- Humans MeSH
- Metronidazole * pharmacology MeSH
- Nitroreductases * genetics metabolism MeSH
- Protozoan Proteins genetics metabolism MeSH
- Trichomonas Vaginitis parasitology MeSH
- Trichomonas vaginalis * genetics drug effects enzymology MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Chile MeSH
- MeSH
- Dysentery, Amebic diagnosis drug therapy complications MeSH
- Ceftriaxone administration & dosage therapeutic use MeSH
- Child MeSH
- Entamoeba histolytica MeSH
- Epiglottitis diagnosis therapy MeSH
- Communicable Diseases * diagnosis epidemiology drug therapy MeSH
- Humans MeSH
- Metronidazole administration & dosage therapeutic use MeSH
- Praziquantel administration & dosage therapeutic use MeSH
- Schistosoma MeSH
- Schistosomiasis mansoni diagnosis epidemiology drug therapy MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Geographicals
- Kenya 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
- Anti-Bacterial Agents therapeutic use administration & dosage MeSH
- Adult MeSH
- Helicobacter pylori * drug effects MeSH
- Helicobacter Infections * drug therapy epidemiology microbiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Metronidazole therapeutic use administration & dosage MeSH
- Stomach Neoplasms * prevention & control epidemiology microbiology MeSH
- Omeprazole * therapeutic use administration & dosage MeSH
- Organometallic Compounds therapeutic use administration & dosage MeSH
- Aged MeSH
- Tetracycline therapeutic use administration & dosage MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
- Geographicals
- China 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
- Cefotaxime therapeutic use MeSH
- Adult MeSH
- Echinococcosis, Hepatic diagnosis therapy MeSH
- Echinococcosis * diagnosis parasitology therapy MeSH
- Humans MeSH
- Metronidazole therapeutic use MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports 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
- Anti-Bacterial Agents therapeutic use MeSH
- Administration, Intravaginal MeSH
- Administration, Oral MeSH
- Vaginosis, Bacterial * drug therapy MeSH
- Dequalinium * therapeutic use MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Middle Aged MeSH
- Humans MeSH
- Metronidazole * therapeutic use MeSH
- Young Adult MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase IV MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial 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
- Medication Adherence * statistics & numerical data MeSH
- Amoxicillin * therapeutic use administration & dosage MeSH
- Anti-Bacterial Agents * therapeutic use adverse effects MeSH
- Bismuth therapeutic use administration & dosage adverse effects MeSH
- Adult MeSH
- Dyspepsia drug therapy microbiology MeSH
- Helicobacter pylori * drug effects MeSH
- Helicobacter Infections * drug therapy MeSH
- Proton Pump Inhibitors * therapeutic use administration & dosage MeSH
- Clarithromycin therapeutic use MeSH
- Drug Therapy, Combination * MeSH
- Middle Aged MeSH
- Humans MeSH
- Metronidazole therapeutic use administration & dosage MeSH
- Prospective Studies MeSH
- Registries * MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Roup dětský (Enterobius vermicularis, E. vermicularis) je aktuálně nejčastějším helmintem lidského střeva. Ze statistik Národní referenční laboratoře pro střevní parazitózy je zřejmé, že je v našich podmínkách téměř jediným zástupcem ze skupiny helmintů (1) (Tab. 1). Vyskytuje se, resp. diagnostikujeme tuto nákazu (enterobióza, oxyurióza) zejména u dětí. Vzhledem k rychlému dozrávání larev ve vajíčku (4–6 hod.), jejich nadprodukci (dospělá samička naklade 5 000–12 000 vajíček (2), (Obr. 1a, b, Obr. 2a, b) a vysoké odolnosti vajíček vůči vnějším vlivům předpokládám současný výskyt u většiny členů rodiny, včetně dospělých. Vzhledem k poměrně vysokému výskytu patogenní trichomonády Dientamoeba fragilis (D. fragilis) ve vzorcích stolice u dětských pacientů se přikláním k hypotéze, kterou vyslovil již v roce 1940 Dobell (3), že právě roup může být vektorem jejich přenosu, a kterou podporuje např. Stark a kol. (4). To naznačují i výsledky studie Prevalence a klinický význam parazitárních infekcí v populaci 0–15letých dětí na Ostravsku, kterou realizovalo naše pracoviště spolu s Dětským oddělením Vítkovické nemocnice. Zde byla D. fragilis přítomna u 26,5 % respondentů, v 11 % společně s E. vermicularis (5). Se zavedením molekulárně biologických diagnostických metod (RT PCR) do rutinní praxe některých laboratoří v ČR se výrazně zvýšil počet jejich nálezů. D. fragilis tak ve statistikách NRL aktuálně již několik let vede (11) (Tab. 2, 3). Způsob přenosu je v zájmu parazitologů (4, 5, 6, 7, 8). Stark a kol. uvádí existenci precystických a cystických stadií (9), nicméně je to i nadále předmětem odborných diskuzí.
Enterobius vermicularis (E. vermicularis) is currently the most common helminth of the human intestine. The statistics of the National Reference Laboratory for Intestinal Parasitoses show that it is almost the only representative of the helminth group in our conditions (1) (Table 1). Occurs or diagnoses this disease (enterobiosis, oxyuriasis) especially in children. Due to the rapid maturation of larvae in the egg (4-6 h), their overproduction (an adult female lays 5 000-12 000 eggs (2) (Fig. 1a, b, Fig. 2a, b) and the high resistance of eggs to external influences, I assume the current occurrence in most family members, including adults. Due to the relatively high prevalence of the pathogenic trichomonad Dientamoeba fragilis (D. fragilis) in stool samples of paediatric patients, I am inclined to the hypothesis, expressed already in 1940 by Dobell (3), that the roup may be the vector of their transmission and which is supported by e.g. Stark et al. (4) This is also suggested by the results of the study Prevalence and clinical significance of parasitic infections in the population of 0-15-year-old children in Ostrava region, which was carried out by our department together with the Children's Department of Vítkovice Hospital.Here, D. fragilis was present in 26,5 % of respondents, in 11% together with E. vermicularis (5). With the introduction of molecular biological diagnostic methods (RT PCR) into the routine practice of some laboratories in the Czech Republic, the number of their findings has increased significantly. Thus, D. fragilis has currently been leading in the NRL statistics for several years (11), (Table 2, 3). The mode of transmission is of interest to parasitologists (4, 5, 6, 7, 8). Stark et al. report the existence of precystic and cystic stages (9), but this remains a matter of professional debate.
- MeSH
- Benzimidazoles therapeutic use MeSH
- Dientamoeba parasitology pathogenicity MeSH
- Child MeSH
- Enterobiasis diagnosis drug therapy transmission MeSH
- Enterobius * parasitology pathogenicity MeSH
- Humans MeSH
- Metronidazole therapeutic use MeSH
- Intestinal Diseases etiology parasitology MeSH
- Intestinal Diseases, Parasitic diagnosis classification parasitology transmission MeSH
- Trichomonadida parasitology pathogenicity MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Review MeSH
Several studies have indicated the beneficial anti-inflammatory effect of butyrate in inflammatory bowel disease (IBD) therapy implying attempts to increase butyrate production in the gut through orally administered dietary supplementation. Through the gut-liver axis, however, butyrate may reach directly the liver and influence the drug-metabolizing ability of hepatic enzymes, and, indirectly, also the outcome of applied pharmacotherapy. The focus of our study was on the liver microsomal cytochrome P450 (CYP) 2A5, which is a mouse orthologue of human CYP2A6 responsible for metabolism of metronidazole, an antibiotic used to treat IBD. Our findings revealed that specific pathogen-free (SPF) and germ-free (GF) mice with dextran sulfate sodium (DSS)-induced colitis varied markedly in enzyme activity of CYP2A and responded differently to butyrate pre-treatment. A significant decrease (to 50%) of the CYP2A activity was observed in SPF mice with colitis; however, an administration of butyrate prior to DSS reversed this inhibition effect. This phenomenon was not observed in GF mice. The results highlight an important role of gut microbiota in the regulation of CYP2A under inflammatory conditions. Due to the role of CYP2A in metronidazole metabolism, this phenomenon may have an impact on the IBD therapy. Butyrate administration, hence, brings promising therapeutic potential for improving symptoms of gut inflammation; however, possible interactions with drug metabolism need to be further studied.
- MeSH
- Anti-Bacterial Agents adverse effects pharmacology therapeutic use MeSH
- Anti-Inflammatory Agents pharmacology MeSH
- Butyrates * pharmacology MeSH
- Metronidazole pharmacology MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Dextran Sulfate adverse effects MeSH
- Gastrointestinal Microbiome * MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Colitis, Ulcerative * chemically induced drug therapy MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Recently, the recommendations for the treatment of Clostridioides difficile infection (CDI) have been updated. However, in addition to the clinical efficacy data, the drug of choice should ideally represent optimal antimicrobial stewardship, with an emphasis on rapid restoration of the gut microbiota to minimize the risk of infection relapses. Oral administration of metronidazole results in low concentration in stool, and interaction with fecal microbiota reduces its antimicrobial bioactivity. Reported elevated minimum inhibitory concentrations of metronidazole in epidemic C. difficile ribotypes and the emergence of plasmid-mediated resistance to metronidazole represent additional potential risks for clinical failure. If metronidazole is the only CDI treatment option, antimicrobial susceptibility testing on agar containing heme should be performed in C. difficile isolate. Compared with metronidazole, oral vancomycin and fidaxomicin reach very high concentrations in the stool, and therefore can quickly reduce C. difficile shedding. Health care facilities with higher CDI incidence and/or occurrence of epidemic ribotypes should not use metronidazole because prolonged C. difficile shedding can increase the risk for further C. difficile transmission. Only fidaxomicin has a narrow spectrum of antimicrobial activity, which might be, together with persistence on spores, the main contributing factor to reduce the recurrent CDI rates.
- MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Clostridioides difficile * MeSH
- Fidaxomicin therapeutic use MeSH
- Clostridium Infections * drug therapy epidemiology microbiology MeSH
- Humans MeSH
- Metronidazole pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH