Search Results (93)

Small intestinal bacterial overgrowth (SIBO) refers to an abnormal increase in the number of bacteria in the small intestine and is observed in various diseases. SIBO can also develop after long-term use of proton pump inhibitors (drug-induced SIBO), bariatric surgery, gastrectomy, and other surgeries (postoperative SIBO). The aim of this narrative review is to summarize all of the published information on the treatment of SIBO in as much detail as possible and present it separately for each specific disease and intervention associated with SIBO. The most extensively studied drug for the treatment of SIBO is rifaximin. It eliminates SIBO in 63% of cases; however, most studies lack a control group. Small RCTs assessing the effects of this antibiotic on SIBO have reported conflicting results, and a meta-analysis showed no effect. A large RCT is required to verify the results of uncontrolled studies. Neomycin and norfloxacin showed efficacy in the treatment of SIBO in single RCTs, with elimination rates of 20 and 100%, respectively. Ciprofloxacin, rifamycin, metronidazole, and other antibiotics, as well as ursodeoxycholic acid, showed positive effects for the treatment of SIBO, but only in uncontrolled studies or in comparison with rifaximin or other drugs. The reported elimination rates were 54%, 67%, 79%, and 75%, respectively. Eradication therapy for Helicobacter pylori infection eliminated SIBO at a rate of approximately 70%. Probiotics have been tested for treatment of SIBO in various diseases. VSL#3 and Saccharomyces boulardii CNCM I-745 were effective in RCTs, with elimination rates of 58% and 80%, respectively. In conclusion, when selecting SIBO treatment regimens, those that have demonstrated the greatest efficacy for a specific concomitant disease should be preferred, despite the generally low level of evidence supporting these approaches in most cases. Full article

Background: Rifaximin is widely used in the management of small intestinal bacterial overgrowth (SIBO), but concerns remain regarding the potential risk of Clostridioides difficile infection (CDI), particularly with repeated antibiotic exposure. Aim: To evaluate the short-term risk of CDI following Rifaximin therapy in patients with SIBO. Materials and Methods: We conducted a retrospective cohort study using the TriNetX Collaborative Research Network. Adult patients with SIBO were identified and categorized based on Rifaximin exposure within 60 days of diagnosis. The primary analysis compared patients with SIBO treated with Rifaximin to those with SIBO who did not receive Rifaximin. Secondary analyses included comparisons between SIBO patients treated with Rifaximin and irritable bowel syndrome (IBS) patients receiving Rifaximin, as well as patients with SIBO receiving a single versus multiple Rifaximin courses. Propensity score matching (1:1) was performed to balance baseline characteristics. The primary outcome was CDI within 60 days of the index event. Secondary outcomes included hospitalization and emergency department (ED) visits. Results: After propensity score matching, 19,597 patients were included in each cohort in the primary comparison of SIBO treated with Rifaximin versus SIBO without Rifaximin. CDI occurred in 0.21% of Rifaximin-treated patients and 0.15% of untreated patients (p = 0.152). In the contextual comparison, CDI incidence was similar between SIBO patients receiving Rifaximin and IBS patients receiving Rifaximin (0.21% vs. 0.15%, p = 0.168). Among patients with SIBO receiving Rifaximin, CDI risk did not differ between single and multiple treatment courses (0.20% vs. 0.21%, p = 0.850). Conclusions: In this large real-world cohort, Rifaximin therapy for SIBO was not associated with a statistically significant increase in short-term CDI risk. However, given the low event rate, wide confidence intervals, and risk of type II error, these findings should be interpreted with caution. Full article

Alterations in the intestinal microbiota have been implicated in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). However, their biological significance and therapeutic implications differ substantially between the two conditions. Although dysbiosis is a common feature, the mechanisms by which alterations in the microbiota contribute to disease pathophysiology and clinical expression are distinct. Some pathways are more prominent in IBS (e.g., the gut–brain axis), whereas others are more prominent in IBD (e.g., reduced microbial diversity). Equally important are pathways that appear to play a role exclusively in IBD [e.g., Adherent-invasive Escherichia coli (AIEC) and Paneth cells], as well as others that seem to be specific to IBS (e.g., mast cell activation). In IBD, microbiota changes are primarily linked to immune dysregulation, mucosal barrier impairment, and inflammation-driven pathways, whereas in IBS, they are mainly associated with functional disturbances mediated by neuroimmune signaling and microbial metabolites. Furthermore, several microbiome-associated biomarkers differ between these two diseases, and some are already assessed by international guidelines. Although the microbiota plays a key role in IBS and IBD pathophysiology, microbiome-based treatments remain limited, especially in IBD. There are clinically available treatments in IBS (e.g., rifaximin, low-FODMAP diet), but in IBD, only the probiotic VSL#3 is guideline-approved in ulcerative colitis pouchitis prophylaxis. Nevertheless, the dynamic nature of the microbiota continues to support the investigation of already studied (e.g., probiotics, fecal microbiota transplantation) and potential novel therapeutic approaches at the research level. The aim of this review is to compare the gut-microbiota-related pathophysiological pathways and biomarkers between IBS and IBD, to summarize the microbiome-related medications that have already been studied in both diseases, and to suggest new potential therapeutic options based on the gut microbiota. Full article

Background and Objectives: Hepatic encephalopathy (HE) management becomes particularly challenging in older patients. This study aimed to evaluate the physician-reported diagnostic approaches, therapeutic strategies, and specific challenges in managing HE in older cirrhotic patients across Italy. Methods: A nationwide survey was conducted under the aegis of the Italian Association for the Study of the Liver (AISF). Forty-three hepatology centres participated. Data were analyzed using descriptive statistics. Results: Participating centers followed over 6000 older patients with cirrhosis, nearly one-third of whom experienced overt HE and/or minimal HE episodes in the previous year. Physicians reported that infections were the most frequently reported precipitating factor, followed by constipation and electrolyte disturbances for OHE. Half of patients with HE (50%; IQR 30.0–50.0%) experienced recurrent episodes, while 22% (IQR 10.0–30.0%) were reported to have persistent HE. In this setting, the diagnosis of HE was often complicated by cognitive decline. Treatment primarily consisted of a combination of lactulose and rifaximin, but adherence was often limited. Caregiver support emerged as a critical element in patient management. The management of comorbidities such as diabetes and chronic kidney disease was a major challenge, and nutritional screening was not routinely implemented across centres. Conclusions: This study highlights the need for better multidisciplinary management, improved caregiver support, and more consistent approaches to the diagnosis and treatment of HE in the elderly. The survey also explored how centres approach the differential diagnosis between HE and age-related cognitive disorders, the practical role of caregivers in outpatient management, and the impact of comorbidities, polypharmacy, and nutritional issues on everyday care. Marked heterogeneity emerged in psychometric assessment, multidisciplinary collaboration, and nutritional screening, indicating that several relevant aspects of care remain insufficiently standardized. Overall, the findings suggest that older patients with HE should be regarded as a distinct high-risk subgroup requiring tailored diagnostic pathways and integrated management models. Full article

Background and Clinical Significance: Hepatic encephalopathy (HE) is a reversible brain dysfunction typically associated with cirrhosis and portal hypertension. In these patients, portosystemic shunts allow ammonia and other toxins to bypass hepatic metabolism, leading to neurological symptoms. However, HE can also occur in non-cirrhotic patients through congenital shunts or, less commonly, through iatrogenic shunts following abdominal trauma or surgery. This case is clinically significant as it illustrates a rare presentation of recurrent HE caused by a de novo portosystemic shunt following major abdominal surgery in a patient without underlying liver disease. Case Presentation: A 76-year-old male was admitted with confusion, lethargy, and flapping tremors. His medical history included a total pancreatectomy for pancreatic adenocarcinoma six months prior. Laboratory tests revealed hyperammonemia and altered liver enzymes likely related to ongoing chemotherapy, but no signs of hepatic insufficiency or cirrhosis. A review of recent CT imaging identified a new portosystemic shunt between the portal territory and the azygous vein that was absent prior to his pancreatectomy. This iatrogenic shunt likely formed via the re-vascularization of vestigial vessels following surgical de-vascularization. The patient was successfully managed with lactulose and rifaximin. At 3-month follow-up, no further HE episodes had occurred. Conclusions: This case highlights that HE should be considered in patients without cirrhosis presenting with altered mental status and hyperammonemia, especially following abdominal surgery. It underscores the importance of a multidisciplinary approach and meticulous re-evaluation of imaging to identify iatrogenic vascular shunts that may be amenable to medical or interventional management. Full article

Rosacea is a chronic skin condition characterized by persistent inflammation, manifesting primarily on the face and causing redness, papules, pustules, and phymatous changes. The etiology of rosacea is multifactorial, with immune system factors playing a crucial role in its pathogenesis. The scientific literature contains an increasing number of studies that suggest a correlation between rosacea and the gut microbiota. Small intestinal bacterial overgrowth (SIBO) is defined as an excessive proliferation of potentially pathogenic bacteria within the small intestine of the gastrointestinal system. Multiple factors have been posited to explain the pathogenesis of rosacea, and the presence of SIBO has been identified as a potential factor in its occurrence. A decrease in the Lactobacillus genus, Prevotella copri, Lachnospiraceae, and Faecalibacterium within the gut microbiota may initiate inflammation related to rosacea. These bacterial species are crucial for regulating the intestinal mucosa. The findings indicate that there is an increase in Bacteriodes, Acidaminococcus, Megasphaera, and Ruminococcus in the gut microbiome of patients with rosacea. Probiotics can be advantageous for managing the intestinal microbiome, while Rifaximin treatment has shown efficacy in addressing inflammatory rosacea lesions associated with SIBO. The present review has been undertaken with the objective of enhancing our comprehension of SIBO in rosacea. The emphasis has been placed on the pathogenetic mechanisms and the shift in the gut microbiota that will lead to understanding probiotic benefits and therapy options in rosacea patients. Full article

Small-intestinal bacterial overgrowth (SIBO) is defined by an excessive microbial presence in the small intestine and is associated with a range of gastrointestinal symptoms. Its management remains complex due to diagnostic limitations and high recurrence rates following treatment. A narrative review was conducted using MEDLINE (PubMed) and Cochrane databases to identify relevant studies published between 1984 and 2024. Search terms included small intestinal bacterial overgrowth SIBO, FODMAP, probiotics, prebiotics, synbiotics, and low-carbohydrate diets. Reference lists were also screened for additional studies. Antibiotics, particularly rifaximin, are commonly used for SIBO treatment but recurrence is frequent. Dietary strategies, such as low-FODMAP and low-carbohydrate diets, may help reduce symptoms, especially in patients with complications like D-lactic acidosis. Evidence for biotic agents (probiotics, prebiotics, synbiotics) is mixed, with limited high-quality studies and inconsistent outcomes. Some probiotic strains show symptom improvement, but effects on breath-test results are variable. A tailored, multidisciplinary approach combining dietary and medical therapies may offer optimal symptom control in SIBO. However, heterogeneity in study designs and limited evidence highlight the need for further research to inform standardised, evidence-based clinical practice. Full article

Metabolic Dysfunction-Associated Steato-Hepatitis (MASH) is a multiple-hit disease. Endotoxins, ethanol, and other metabolites of certain gut microbiota can reach the liver and accelerate inflammation and disease progression. Targeting ethanol-producing colonic bacteria with rifaximin could affect the progress of MASH. In the present study, thirty mice were assigned to three groups (n = 10 mice per group). Mice received either a normal diet, a Western diet, or a Western diet with oral rifaximin. After 12 weeks, liver function, serum levels of TNF-α, interleukin (IL)-1β, IL-6, and lipopolysaccharides (LPS) were measured. Liver specimens were assessed for pathological changes, lipid deposition, and fibrosis. Expression of p53, GFAP, CD68, and TLR-4 in the liver was also assessed. Faecal samples were evaluated for ethanol contents. Lactobacillus acidophilus, in addition to ethanol-producing Klebsiella pneumoniae and Escherichia coli, were isolated, quantified, and tested for sensitivity to rifaximin. Rifaximin was able to ameliorate Western diet-induced biochemical changes and elevated TNF-α, IL-1β, IL-6, and LPS levels. Changes in liver histology, fibrosis, and lipid content were attenuated. Expressions of p53, GFAP, CD68, and TLR-4 in the liver were all reduced. The Western diet-induced increases in faecal ethanol or ethanol-producing bacteria were not corrected by rifaximin. After 12 weeks, isolated bacteria from the rifaximin group were rifaximin-resistant. Our findings imply that the protective impact of rifaximin in the MASH model is unlikely to be mediated by alteration of ethanol-producing colonic bacteria because of acquired rifaximin resistance. Rifaximin-induced reduction in endotoxemia and inflammation in the liver appears to be a more relevant explanation. Full article

Background: Rifaximin is a non-aminoglycoside antibiotic utilized for the treatment of mastitis in cows, but its milk disposition kinetics, residue, and bacteriological status in lactating cow milk have hardly been reported. This study aimed to assess the milk disposition kinetics and residue of rifaximin in milk and to evaluate the bacteriological status in milk after intramammary treatment with rifaximin. Methods: An ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) approach was developed to assess rifaximin concentrations in milk. Milk disposition kinetics parameters of rifaximin in cow milk were obtained by non-compartment model analysis. Rifaximin residues in milk were analyzed up to 108 h post-administration to estimate the withdrawal period. Clinically, the efficacy of Rifaximin Intramammary Infusion (Lactating Cow) was evaluated in mastitis cases caused by various pathogens and compared with lincomycin as the control drug, including clinical cure rate, bacteriological cure rate, and somatic cell count (SCC) at D21 post-treatment. Results: The C_max of rifaximin in milk was 54,273.3 ± 12,421.32 ng/mL, the area under the curve (AUC) was 340,731.8 ± 43,968.82 h⋅ng/mL, the T_1/2 was 5.57 ± 0.68 h, the mean resident time (MRT) was 7.3927 ± 1.34 h, and the area under the moment curve (AUMC) was 2,475,745 ± 230,305.1 h⋅h⋅ng/mL. Based on rifaximin residues in milk, the withdrawal period for cow milk was calculated to be 95.1 h. Clinically, Rifaximin Intramammary Infusion (Lactating Cow) demonstrated a clinical cure rate of 83.33% and a bacteriological cure rate of 76.67% in mastitis cases caused by various pathogens, with both rates being 10% higher than those of lincomycin. At D21 post-treatment, the rifaximin group had a significantly lower SCC than the lincomycin group (p < 0.05). Conclusions: Rifaximin exhibits favorable milk disposition kinetics, an acceptable withdrawal period of 95.1 h, and good clinical and bacteriological cure rates in bovine mastitis. These findings support rifaximin as a useful intramammary option and contribute to rational antimicrobial use and milk safety in dairy. Full article

Small Intestinal Bacterial Overgrowth (SIBO) is characterized by an abnormal proliferation of bacteria in the small intestine, leading to gastrointestinal symptoms and nutritional deficiencies. Short Bowel Syndrome (SBS), resulting from extensive surgical resection of the small intestine, predisposes children to SIBO due to anatomical disruptions, motility dysfunction, parenteral nutrition dependence, and immune dysregulation. Clinical manifestations of SIBO in SBS include bloating, diarrhea, malabsorption, and failure to thrive, with severe cases leading to complications such as D-lactic acidosis. Diagnosis remains challenging, with breath testing being the most commonly used method despite limitations in accuracy, especially in SBS patients. Jejunal aspiration, the gold standard, presents limitations due to contamination risks, potential for sampling error, and a relatively low diagnostic yield. Management involves antibiotics like rifaximin and metronidazole, alongside strategies to address anatomical dysfunction, optimize nutrition, and prevent recurrence. Adjunctive therapies, including probiotics and dietary modifications, show promise but require further validation in children. Emerging treatments, such as glucagon-like peptide-2 (GLP-2) analogs, may enhance mucosal integrity and reduce SIBO risk. Given the chronic and recurrent nature of SIBO in SBS, a multidisciplinary approach is essential, integrating gastroenterological, surgical, and nutritional care to effectively manage the condition. Future research should focus on improving diagnostic methods, refining treatment protocols, and exploring targeted therapies to enhance outcomes and quality of life for affected children. Full article

Background: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of advanced liver disease, driven primarily by ammonia accumulation due to impaired hepatic detoxification and portosystemic shunting. Lactulose is a cornerstone therapy, while rifaximin serves as an effective adjunct for reducing recurrence and hospitalizations. Methods: We conducted a retrospective cohort study at Constanța Emergency County Hospital from January 2022 to March 2025, including 120 adult patients diagnosed with HE. Inclusion criteria were confirmed diagnosis of cirrhosis with clinical and/or biochemical evidence of HE. Patients with other primary neurological disorders or incomplete medical records were excluded. Data on demographics, comorbidities, laboratory results, and medications were collected. Statistical analyses were performed employing descriptive statistics, Friedman’s two-way ANOVA by ranks for medication use, and Cox proportional hazards regression to assess survival associations. Results: The mean age was 61.19 years, with high prevalence of anemia (mean hemoglobin: 9.35 g/dL) and thrombocytopenia (mean: 121.86 × 10³/µL). Inflammatory markers were elevated (mean CRP: 36.95 mg/L; ESR: 55.83 mm/h), and INR averaged 1.86. Lactulose was administered to 63.3% of patients, rifaximin to 52.5%, with diuretics, pantoprazole, and albumin being frequently used. Friedman’s analysis ranked lactulose highest in usage frequency. Cox regression indicated no significant short-term survival difference associated with toxic encephalopathy or rifaximin use. Conclusion: In this cohort, lactulose remained the primary treatment for HE, often complemented by supportive pharmacotherapy. While rifaximin use was limited, the overall medication patterns reflected standard practice priorities in HE management. Full article

Objectives: Rifaximin is a non-absorbable antibiotic that has an efficacy for hepatic encephalopathy (HE). We previously demonstrated that rifaximin improved liver functional reserve, but this was a single-center study with a limited number of cases, and there were few cases of long-term use. Here, we conducted a multicenter study to evaluate the efficacy of long-term rifaximin administration on the liver functional reserve. Methods: A multicenter retrospective study was conducted on cirrhotic patients who received rifaximin for more than 12 months. We evaluated the efficacy of long-term rifaximin administration on the liver functional reserve. Results: A total of 65 cirrhotic patients were enrolled. Administration of rifaximin for 12 months significantly improved the Child–Pugh score (CPS) and albumin–bilirubin (ALBI) score. Regarding the parameters of the CPS, albumin scores significantly improved in addition to HE scores at 12 months. Univariate and multivariate analysis revealed that high C-reactive protein (CRP) levels (>0.69 mg/dL) at baseline were the predictive factor for improvement in the liver functional reserve. Conclusions: This study suggests that long-term rifaximin administration may improve the liver functional reserve in cirrhotic patients through improvement in albumin levels. CRP levels predict improvement in the liver functional reserve. Full article

Background/Objectives: Antimicrobial resistance (AMR) remains a major topic of interest in infectious disease management. We studied AMR in Clostridioides difficile isolated in Cambodia. Methods: Agar dilution susceptibility testing was performed according to the CLSI guidelines to determine minimal inhibitory concentrations (MICs) of 10 antimicrobials for 192 isolates of C. difficile from four populations in Cambodia: hospitalised adults, hospitalised children, children from an outpatient department (OPD), and healthy adolescents in the community. Results: Using the CLSI MIC breakpoints for anaerobes and EUCAST breakpoints for C. difficile, all isolates were susceptible to vancomycin, metronidazole, fidaxomicin, and amoxicillin/clavulanic acid, and none were resistant to meropenem. The resistance proportions were for clindamycin, 88% (169/192); tetracycline, 50% (96/192); moxifloxacin, 20% (38/192); and rifaximin, 8% (15/192). Among the 169 clindamycin-resistant isolates, 56.8% (96/169) had an erythromycin MIC of >512 mg/L. Multidrug resistance (MDR) occurred in 20% (39/192) of the isolates, of which 82% (32/39) were non-toxigenic strains. The proportion of MDR varied between collections of isolates from different populations: 28.6% (22/77) in hospitalised adults, 29.8% (14/47) in hospitalised children, 5% (3/59) in OPD children, and none (00/07) in healthy adolescents in the community. Conclusions: C. difficile isolates from Cambodia remained susceptible to antimicrobials used to treat C. difficile infection: vancomycin, metronidazole, and fidaxomicin; however, high proportions of resistance to clindamycin and tetracycline were observed. The high number of MDR strains of C. difficile is a threat to AMR management in Cambodia and a factor contributing to the persistent spread of C. difficile in both hospital and community settings. Full article

Background/Objectives: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption of liver tissue, with transforming growth factor-β (TGF-β) signaling and inflammatory mediators as central pathways. Current therapies primarily target the underlying causes, which may halt disease progression but rarely reverse established fibrosis. This review aims to outline current and emerging therapeutic strategies for liver fibrosis, informing both clinical practice and future research directions. Methods: A narrative synthesis of preclinical and clinical evidence was conducted, focusing on pharmacological interventions, microbiota-directed strategies, and innovative modalities under investigation for antifibrotic activity. Results: Bile acids, including ursodeoxycholic acid and derivatives, modulate HSC activity and autophagy. Farnesoid X receptor (FXR) agonists, such as obeticholic acid, reduce fibrosis but are limited by adverse effects. Fatty acid synthase inhibitors, exemplified by denifanstat, show promise in metabolic dysfunction-associated steatohepatitis (MASH). Additional strategies include renin–angiotensin system inhibitors, omega-3 fatty acids, and agents targeting the gut–liver axis. Microbiota-directed interventions—probiotics, prebiotics, symbiotics, antibiotics (e.g., rifaximin), and fecal microbiota transplantation—are emerging as potential modulators of barrier integrity, inflammation, and fibrogenesis, though larger clinical trials are required. Reliable non-invasive biomarkers and innovative trial designs, including adaptive platforms, are essential to improve patient selection and efficiently evaluate multiple agents and combinations. Conclusions: Novel modalities such as immunotherapy, gene editing, and multi-targeted therapies hold additional potential for fibrosis reversal. Continued translational efforts are critical to establish safe, effective, and accessible treatments for patients with liver fibrosis. Full article

Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. Full article