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Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE. Twenty cirrhotics with MHE underwent cognitive testing, endotoxin analysis, urine/serum metabolomics (GC and LC-MS) and fecal microbiome assessment (multi-tagged pyrosequencing) at baseline and 8 weeks post-rifaximin 550 mg BID. Changes in cognition, endotoxin, serum/urine metabolites (and microbiome were analyzed using recommended systems biology techniques. Specifically, correlation networks between microbiota and metabolome were analyzed before and after rifaximin. There was a significant improvement in cognition(six of seven tests improved, p<0.01) and endotoxemia (0.55 to 0.48 Eu/ml, p = 0.02) after rifaximin. There was a significant increase in serum saturated (myristic, caprylic, palmitic, palmitoleic, oleic and eicosanoic) and unsaturated (linoleic, linolenic, gamma-linolenic and arachnidonic) fatty acids post-rifaximin. No significant microbial change apart from a modest decrease in Veillonellaceae and increase in Eubacteriaceae was observed. Rifaximin resulted in a significant reduction in network connectivity and clustering on the correlation networks. The networks centered on Enterobacteriaceae, Porphyromonadaceae and Bacteroidaceae indicated a shift from pathogenic to beneficial metabolite linkages and better cognition while those centered on autochthonous taxa remained similar. Rifaximin is associated with improved cognitive function and endotoxemia in MHE, which is accompanied by alteration of gut bacterial linkages with metabolites without significant change in microbial abundance. ClinicalTrials.gov NCT01069133.

Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE. In this prospective double-blind randomized controlled trial, 120 patients with overt HE were randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay. A total of 120 patients (mean age 39.4±9.6 years; male/female ratio 89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7±2.8 and the MELD (model for end-stage liver disease) score was 24.6±4.2. At the time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and 58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29 (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8±3.4 vs. 8.2±4.6 days, P=0.001). Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.

In two trials involving patients with irritable bowel syndrome without constipation, 2 weeks of treatment with the minimally absorbed antibiotic rifaximin was more effective than placebo in providing adequate relief of symptoms. The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by recurring symptoms of abdominal pain, bloating, and altered bowel function in the absence of structural, inflammatory, or biochemical abnormalities. 1 IBS often does not respond to current treatment options, including dietary and lifestyle modifications, fiber supplementation, psychological therapy, and pharmacotherapy. 2 , 3 Because no reliable biologic or structural markers have been identified, the effects of pharmacotherapy are typically assessed by asking patients to report whether they had adequate relief of IBS symptoms (with a binary response of yes or no). 4 Given the limitations of available therapies, there is an unmet . . .

In this placebo-controlled, randomized trial of patients with a history of recurrent hepatic encephalopathy resulting from chronic liver disease, rifaximin (at a dose of 550 mg twice daily) prevented episodes of hepatic encephalopathy and hospitalizations involving hepatic encephalopathy. In patients with a history of recurrent hepatic encephalopathy resulting from chronic liver disease, rifaximin prevented episodes of hepatic encephalopathy and hospitalizations involving hepatic encephalopathy. Approximately 5.5 million persons in the United States have hepatic cirrhosis, a major cause of complications and death. 1 – 3 Hepatic encephalopathy, a complication of hepatic cirrhosis, imposes a formidable burden on patients, their families, and the health care system. 1 , 4 Overt episodes of hepatic encephalopathy are debilitating, can occur without warning, render the patient incapable of self-care, and frequently result in hospitalization. 1 , 4 In 2003, more than 40,000 patients were hospitalized with hepatic encephalopathy, a number that increased to over 50,000 in 2004. 4 Although the occurrence of episodes of hepatic encephalopathy appears to be unrelated to the cause of cirrhosis, . . .

Antimicrobial resistance (AMR) threatens global health, particularly through the rise of multidrug-resistant tuberculosis (MDR-TB) and other critical bacterial infections such as methicillin-resistant Staphylococcus aureus (MRSA). Rifamycins remain frontline antibiotics but are increasingly undermined by resistance. Here, we introduce a click-enabled platform for the synthesis of C8-functionalized rifamycins, which can be converted in a single additional step into efficacious 3′-hydroxy-5′-aminobenzoxazinorifamycins (bxRifs) and enzymatically into 25-deacetylated rifamycins (deAcRifs), providing access to novel antibacterial scaffolds that expand beyond the scope of traditional C8 modifications. Accordingly, we establish a modular strategy for late-stage analog development of the complex natural product rifamycin S, wherein azido and alkyne functionalities are installed via tailored core chemistry and converted into 1,2,3-triazoles through copper(I)-catalyzed click chemistry. Another key feature of this work is the development of systematic HPLC purification methods, enabling the isolation of analytically pure compounds despite structural complexity. The resulting analogs exhibit distinct antibacterial profiles, notably against Gram-positive bacteria including MRSA and Streptococcus mutans, informing structure–activity relationships and offering a foundation for further optimization. This approach supports the rapid diversification of rifamycin scaffolds to combat the escalating threat of AMR, while also establishing a foundation for future discovery through bioorthogonal applications.

Travelers' diarrhea causes substantial morbidity and postinfectious irritable bowel syndrome. To evaluate nonabsorbable rifaximin for prevention of travelers' diarrhea. Randomized, double-blind, placebo-controlled clinical trial. Guadalajara, Mexico. U.S. students. On arrival in Guadalajara, Mexico, 210 U.S. adults received rifaximin (200 mg/d, 200 mg twice daily, or 200 mg 3 times daily) or placebo for 2 weeks. Participants were followed daily for 3 weeks for enteric disease and symptoms and daily for 5 weeks for drug side effects. Changes in intestinal coliform flora were studied. Travelers' diarrhea developed in 14.74% of participants taking rifaximin and 53.70% of those taking placebo (rate ratio, 0.27 [95% CI, 0.17 to 0.43]). Rifaximin provided 72% and 77% protection against travelers' diarrhea and antibiotic-treated travelers' diarrhea, respectively (P < 0.001 for both), and all rifaximin doses were superior to placebo. In the groups that did not report travelers' diarrhea, rifaximin significantly reduced the occurrence of mild diarrhea (P = 0.02) and moderate and severe intestinal problems (P = 0.009 for pain or cramps; P = 0.02 for excessive gas). Rates of adverse events were comparable in the rifaximin and placebo groups. Minimal changes in coliform flora were found during rifaximin therapy. Rifaximin safely prevented travelers' diarrhea in Mexico, where most cases are caused by diarrhea-producing Escherichia coli. A study is needed in Asia to determine whether rifaximin can prevent diarrhea caused by invasive bacterial pathogens. Rifaximin prevents travelers' diarrhea with minimal changes in fecal flora, and more liberal chemoprophylaxis against this disease should be considered. Future studies should evaluate whether rifaximin is effective in preventing postinfectious irritable bowel syndrome.

Helichrysum stoechas is a singular halophyte that has been shown to have anti-inflammatory, antioxidant, and allelopathic properties. In the work presented herein, we have characterized its inflorescences hydromethanolic extract and assessed its antifungal activity for the pre- and postharvest management of tomato crop diseases. Gas chromatography–mass spectrometry characterization of the extract showed that 4-ethenyl-1,3-benzenediol, 2,3-dihydro-benzofuran, quinic acid, 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-1-benzopyran-4-one, 1,6-anhydro-β-D-glucopyranose, catechol, scopoletin, and maltol were the main constituents. The co-occurrence of pyranones, benzenediols, and quinic acids as phytoconstituents of H. stoechas extract resulted in promising in vitro minimum inhibitory concentrations of 500, 375, 500, 187.5, 187.5, and 375 μg·mL[sup.−1] against mycelia of Alternaria alternata, Colletotrichum coccodes, Fusarium oxysporum f. sp. lycopersici, Rhizoctonia solani, Sclerotinia sclerotiorum, and Verticillium dahliae, respectively. Further, to assess the potential of H. stoechas inflorescence extract for postharvest tomato crop protection, ex situ tests were conducted against C. coccodes, obtaining high protection at a dose of 750 μg·mL[sup.−1]. Taking into consideration that the demonstrated activity is among the highest reported to date for plant extracts and comparable to that of the synthetic fungicides tested as positive controls, H. stoechas inflorescence extract may be put forward as a promising biorational and may deserve further testing in field-scale studies.

Background The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects. Aims To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects. Methods A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18–65 with C-IBS (Rome II criteria) and breath methane (>3 ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2 weeks of therapy and 4 additional weeks of follow-up. Results Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6 ± 30.8) compared to neomycin alone (61.2 ± 24.1) ( P  = 0.0042), with greater improvement in constipation ( P  = 0.007), straining ( P  = 0.017) and bloating ( P  = 0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3 ppm after treatment reported significantly lower constipation severity (30.5 ± 21.8) than subjects with persistent methane (67.2 ± 32.1) ( P  = 0.020). Conclusions Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.

Antibiotics have demonstrated efficacy in the eradication of the underlying overgrowth bacteria and improvement of symptoms of small intestinal bacterial overgrowth (SIBO). The use of standard antibiotics may cause intolerable side effects such as development of multidrug-resistant enteric bacteria, Clostridioides difficile infections and dysbiosis. Nonabsorbable antibiotics have the advantage of minimized side effects. Rifaximin, an antibiotic of the ansamycin class has been shown to be effective in the treatment of SIBO. We evaluated the use of another ansamycin antibiotic, rifamycin SV MMX (AEMCOLO) in the treatment of SIBO. One difference from rifaximin is the site of delivery of AEMCOLO which appears to be the distal small intestine and colon. Hence by maintaining the microbial milieu of the proximal small intestine, the clearance of the overgrowth bacteria might be enhanced. The side effect profile of Rifamycin SV MMX has been described elsewhere in the pivotal trials; there were no safety signals noted in this study. This randomized open label pilot study evaluated the efficacy of two dosing regimens of AEMCOLO in treating SIBO. We used a simple randomization method to assign participants into study groups. The participants included 31 patients, split between two treatment arms: one receiving the medication twice daily and the other - three times daily. The outcomes were assessed based on symptom improvement and breath test normalization. The results indicated a beneficial response with both dosing regimens leading to symptom improvement and breath test normalization. Further evaluation revealed that in the three-time daily regimen, greater symptomatic improvement was observed. For clinicians treating SIBO, this study suggests that AEMCOLO is a viable treatment option. A double-blind, placebo-controlled design will probably be necessary to ascertain the true efficacy of different dosing regimens of AEMCOLO in treating SIBO.