Oral Nonabsorbable Antibiotics Research Articles

Portal Systemic Encephalopathy without Significant Changes of Chronic Liver Disease

Introduction: Determining the etiology of an encephalopathy can be challenging for the neurologists, especially when the preliminary investigations do not indicate any significant biochemical or other systemic abnormality. Portosystemic shunts maybe easily missed and may present as recurrent encephalopathy with elevated serum ammonia or cerebrospinal glutamate levels. These shunts maybe easily identified in the presence of overt chronic liver disease, but maybe easily missed in patients with cryptogenic liver disease or in congenital abnormalities of the intrahepatic vascular system without an associated chronic liver disease. Materials and Methods: The triple-phase computed tomography (CT) or contrast magnetic resonance imaging can demonstrate the extent of portal vein thrombosis, map the extent of the portosystemic collateral, and aid in planning the treatment in patients with difficult anatomy of the portosystemic collaterals. Treatment regimens for patients with portosystemic shunts manifesting as hyperammonemic encephalopathy include restriction of oral protein intake, lactulose administration, oral nonabsorbable antibiotics, closure of the endovascular shunt, or finally, liver transplant. We present a case of a 55-year-old female with seizure disorder presenting with recurrent episodes of encephalopathy with elevated serum ammonia without the overt signs of chronic liver disease with identification of portosystemic shunting on a triple-phase CT of the abdomen. Conclusion: Specialized investigations to identify the presence of portosystemic collaterals should be conducted in patients with cryptogenic encephalopathy with elevated serum ammonia.

Harnessing the microbiome to regulate systemic innate immunity

Abstract The mechanisms used by the gastrointestinal microbiome to regulate systemic immunity remain unclear. We have identified a microbiome Bacteroidota-derived lipopeptide—L654—that is a TLR2 ligand, accesses the systemic circulation, and thus potentially links the microbiome and systemic innate immunity. We previously documented that Multiple Sclerosis patients have significantly lower serum L654 levels than healthy controls, leading us to postulate that: 1) L654 regulates systemic innate immunity by entering the systemic circulation and mediating TLR2 interactions that maintain “normal” levels of innate immune signaling feedback inhibitors; and 2) inadequate systemic L654 levels result in poorly regulated, enhanced innate immune responses. In prior proof-of-concept studies, we reported that increasingsystemic L654 levels by administering exogenous L654 intravenously significantly diminishessystemic innate immune responses and attenuates murine autoimmunity. In the present study, our goal was to document the converse effect, i.e., that decreasingmicrobiome L654 production enhancessystemic innate immune responses. Using wild-type C57BL/6 mice, we report that decreasing microbiome Bacteroidota using specific non-absorbable oral antibiotics reduces fecal and serum L654 levels and significantly enhances innate immune responses. Moreover, the intravenous administration of L654 to antibiotic-treated mice prevents this innate immune enhancement. Overall, our results suggest that L654 is: 1) used by the microbiome to regulate systemic innate immunity; and 2) a manipulatable target capable of enhancing or decreasing innate immunity in the context of infectious, malignant, or autoimmune diseases. UConn Health Center Academic Advancement Fund

An overview of diverticular pathophysiology and its treatment

Diverticula are protrusions that resemble sacs in the colon's wall. Acute or chronic problems are experienced by 4% of diverticula patients. Diverticulosis development has been linked in large part to the western way of life. Colonic diverticular disease has become more common. Obesity, smoking, and inadequate fibre consumption are risk factors for the illness. Most of the time, surgery is not necessary to treat this; however, if the bleeding is significant, angiography and endovascular intervention may be helpful. Ureteral catheters should be considered when a patient has undergone radiation therapy, resurgery, or preoperative imaging reveals an abnormal anatomy. Oral antibiotics can help prevent surgical site infections after an elective colon resection, according to studies. Using nonabsorbable oral antibiotics like erythromycin, neomycin, and metronidazole reduces surgical site infections overall.

Early-Life Exposure to Non-Absorbable Broad-Spectrum Antibiotics Affects the Dopamine Mesocorticolimbic Pathway of Adult Rats in a Sex-Dependent Manner.

Gut microbiota with a stable, rich, and diverse composition is associated with adequate postnatal brain development. Colonization of the infant’s gut begins at birth when parturition exposes the newborn to a set of maternal bacteria, increasing richness and diversity until one to two first years of age when a microbiota composition is stable until old age. Conversely, alterations in gut microbiota by diet, stress, infection, and antibiotic exposure have been associated with several pathologies, including metabolic and neuropsychiatric diseases such as obesity, anxiety, depression, and drug addiction, among others. However, the consequences of early-life exposure to antibiotics (ELEA) on the dopamine (DA) mesocorticolimbic circuit are poorly studied. In this context, we administered oral non-absorbable broad-spectrum antibiotics to pregnant Sprague-Dawley dams during the perinatal period (from embryonic day 18 until postnatal day 7) and investigated their adult offspring (postnatal day 60) to assess methylphenidate-induced conditioned place preference (CPP) and locomotor activity, DA release, DA and 3,4-dihydroxyphenylacetic acid (DOPAC) content in ventral tegmental area (VTA), and expression of key proteins within the mesocorticolimbic system. Our results show that ELEA affect the rats conduct by increasing drug-seeking behavior and locomotor activity induced by methylphenidate of males and females, respectively, while reducing dopamine striatal release and VTA content of DOPAC in females. In addition, antibiotics increased protein levels of DA type 1 receptor in prefrontal cortex and VTA of female rats, and tyrosine hydroxylase in VTA of adult male and female rats. Altogether, these results suggest that ELEA alters the development of the microbiota-gut-brain axis affecting the reward system and the response to abuse drugs in adulthood.

RISE OF RIFAXIMIN IN PAEDIATRIC INFECTIOUS DIARRHOEA

The incidence and risk of morality is high under the age of five years is due to diarrhoea. In India twenty percentages of paediatric deaths is due to diarrhoeal disease. It is the second cause of leading mortality in children after acute respiratory infections. Following on from the GEMS study when we looked at the data in the management of bacterial diarrhoea the primary treatments included oral rehydration solution, oral zinc probiotics and antibiotics. Anecdotally we noted that a lot of children were treated with oral antibiotics and the majority of them were treated with fluoroquinolones like Ofloxacin and drugs like Metronidazole there are multiple side-effects associated with the usage of fluoroquinolones and a major side-effect of that is the risk to the growing cartilage. We also noticed that irrational combinations such as imidazole like metronidazole have shown more problems than solutions .usage of Ofloxacin in children should be discouraged for all the side-effects plus the infectivity in the management of bacterial diarrhoea. The duration of treatment have paved the way for usage of drugs such as new molecules in paediatric i.e. rifaximin comes under the group of oral non-absorbable GI antibiotics broad-spectrum agents with antibacterial activity against gram positive and gram negative aerobes and Anaerobes makes Rifaximin a bactericidal drug in nature. Rifaximin is particularly recommended in children above the age of two years in acute infectious diarrhoea the mechanism of action of rifaximin is by inhibition of bacterial protein synthesis by reversibly binding to bacterial DNA dependent RNA polymerase. In this review we discussed the “phrma” behind rifaximin, clinical experience of rifaximin in children and indications and dosage of rifaximin in paediatric.

Rifaximin as a Potential Treatment for IgA Nephropathy in a Humanized Mice Model.

: BackgroundIgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Rifaximin (NORMIX®), a non-absorbable oral antibiotic, induces positive modulation of the gut microbiota, favoring the growth of bacteria beneficial to the host. Here, we evaluate the effect of rifaximin on a humanized mice model of IgAN (α1KI-CD89Tg). Methods: The α1KI-CD89Tg mice were treated by the vehicle (olive oil) or rifaximin (NORMIX®). Serum levels of hIgA, hIgA1–sCD89, and mIgG–hIgA1 immune complexes were determined. Glomerular hIgA1 deposit and CD11b+ cells recruitment were revealed using confocal microscopy. Furthermore, the mRNA of the B-Cell Activating Factor (BAFF), polymeric immunoglobulin receptor (pIgR), and Tumor Necrosing Factor-α (TNF-α) in gut samples were detected by qPCR. Results: Rifaximin treatment decreased the urinary protein-to-creatinine ratio, serum levels of hIgA1–sCD89 and mIgG–hIgA1 complexes, hIgA1 glomerular deposition, and CD11b+ cell infiltration. Moreover, rifaximin treatment decreased significantly BAFF, pIgR, and TNF-α mRNA expression. Conclusions: Rifaximin decreased the IgAN symptoms observed in α1KI-CD89Tg mice, suggesting a possible role for it in the treatment of the disease.

Pharmacokinetics and Safety of Rifamycin SV after Single and Multiple Doses of MMX® Modified Release Tablets in Healthy Male and Female Volunteers.

The primary objective of this single- and multiple-dose pharmacokinetic study was the investigation of rifamycin SV’s pharmacokinetic profile in plasma and urine. All the 18 enrolled healthy men and post-menopausal women received modified release tablets containing 600 mg of the oral non-absorbable antibiotic, rifamycin SV, according to a multiple dose regimen: one tablet three times a day (daily intake: 1800 mg) for 14 consecutive days. Blood sampling and urine collection were performed up to 24 h post-dose after the first dose on Days 1 and 7. On average, on Day 1, Cmax,0–24 was 5.79 ± 4.24 ng/mL and was attained in a median time of 9 h. On Day 7, all the subjects had quantifiable levels of rifamycin SV in plasma at each sampling time. After a peak concentration attained 2 h post-dose (mean ± SD concentration: 10.94 ± 16.41 ng/mL), rifamycin SV decreased in plasma to levels similar to those of Day 1. The amounts of rifamycin SV excreted in urine paralleled the plasma concentration at the corresponding times. On Day 1, the total amount excreted in urine was 0.0013%, and was 0.0029% on Day 7. The study results confirmed those of the previous Phase I study: the systemic absorption of rifamycin SV was also proved negligible after 7 days of the 600 mg t.i.d. dose regimen of the newly formulated tablets, currently under development for the treatment of several small and large intestinal pathologies, including diarrhea-predominant irritable bowel syndrome, hepatic encephalopathy, and others. Registered at ClinicalTrials.gov with the identifier NCT02969252, last updated on 26JAN18.

Factors Associated With Short-Term Eradication of Rectal Colonization by KPC-2 Producing Klebsiella pneumoniae in an Outbreak Setting.

Background: KPC-producing Klebsiella pneumoniae (KPCKP) is a threat for patients admitted to healthcare institutions.Objectives: To assess the efficacy of several decolonization strategies for KPCKP rectal carriage.Methods: Observational study performed in a 750-bed university center from July to October 2018 on the efficacy of a 10-day non-absorbable oral antibiotic (NAA) regimen (colistin 10 mg/ml, amikacin 8 mg/ml, and nystatin 30 mg/ml, 10 ml/6 h) vs. the same regimen followed by a probiotic (Vivomixx®) for 20 days in adult patients with KPCKP rectal colonization acquired during an outbreak.Results: Seventy-three patients colonized by KPCKP were included, of which 21 (29%) did not receive any treatment and 52 (71.2%) received NAA either alone (n = 26, 35.6%) or followed by a probiotic (n = 26, 35.6%). Eradication was observed in 56 (76.7%) patients and the only variable significantly associated with it was not receiving systemic antibiotics after diagnosis of rectal carriage [22/24 (91.6%) vs. 34/49 (69.3%), p = 0.04]. Eradication in patients receiving NAA plus probiotic was numerically but not significantly higher than that of controls [23/26 (88.4%) vs. 15/21 (71.4%), p = 0.14] and of those receiving only NAA (OR = 3.4, 95% CI = 0.78–14.7, p = 0.09).Conclusion: In an outbreak setting, rectal carriage of KPCKP persisted after a mean of 36 days in about one quarter of patients. The only factor associated with eradication was not receiving systemic antibiotic after diagnosis. A 10-day course of NAA had no impact on eradication. Probiotics after NAA may increase the decolonization rate, hence deserving further study.

Innate gut microbiota predisposes to high alcohol consumption.

Gut microbiota is known to be transferred from the mother to their offspring. This study determines whether the innate microbiota of rats selectively bred for generations as high alcohol drinkers play a role in their alcohol intake. Wistar-derived high-drinker UChB rats (intake 10-g ethanol/kg/day) administered nonabsorbable oral antibiotics before allowing access to alcohol, reducing their voluntary ethanol intake by 70%, an inhibition that remained after the antibiotic administration was discontinued. Oral administration of Lactobacillus rhamnosus Gorbach-Goldin (GG) induced the synthesis of FGF21, a vagal β-Klotho receptor agonist, and partially re-invoked a mechanism that reduces alcohol intake. The vagus nerve constitutes the main axis transferring gut microbiota information to the brain ("microbiota-gut-brain" axis). Bilateral vagotomy inhibited rat alcohol intake by 75%. Neither antibiotic treatment nor vagotomy affected total fluid intake. A microbiota-mediated marked inflammatory environment was observed in the gut of ethanol-naïve high-drinker rats, as gene expression of proinflammatory cytokines (TNF-α; IL-6; IL-1β) was significantly reduced by nonabsorbable antibiotic administration. Gut cytokines are known to activate the vagus nerve, while vagal activation induces pro-rewarding effects in nucleus accumbens. Both alcoholics and alcohol-preferring rats share a marked preference for sweet tastes-likely an evolutionary trait to seek sweet fermented fruits. Saccharin intake by UChB rats was inhibited by 75%-85% by vagotomy or oral antibiotic administration, despite saccharin-induced polydipsia. Overall, data indicate that the mechanisms that normally curtail heavy drinking are inhibited in alcohol-preferring animals and inform a gut microbiota origin. Whether it applies to other mammals and humans merits further investigation.

Role of non-absorbable oral antibiotics in bowel preparation for intracavitary brachytherapy: effects of rifaximin on rectal dosimetric parameters during vaginal cuff brachytherapy.

PurposeBrachytherapy is a major tool for dose escalation in gynecological cancer treatment. Control of rectal repletion is particularly challenging; it can impact dose received by this organ at risk and there are reported toxicities. The use of methods, such as enema and bowel preparation, to reduce rectal volume is a difficult process for patients, and its repeatability requires patients’ cooperation. Due to the effect of antibiotics on reducing intestinal gases, this study was conducted to measure the effect of adding rifaximin to bowel preparation on rectal dose-volume histogram (DVH) parameters.Material and methodsIn this prospective interventional study, 24 patients with cervical and endometrial cancer were treated with adjuvant high-dose-rate (HDR) brachytherapy. Both first and second sessions of brachytherapy were performed with bowel preparation, before and after the administration of rifaximin, respectively. The rectum was contoured as an organ at risk, and DVH parameters were recorded and compared in both sessions using magnetic resonance imaging (MRI)-based 3D treatment planning system.ResultsRifaximin consumption reduced the rectal volume (p = 0.01), but had no significant correlation with other DVH parameters, especially D2cc (p = 0.599). Moreover, rectal volume had no significant correlation with DVH parameters (all p-values ≤ 0.05).ConclusionsEven though the addition of rifaximin to bowel preparation significantly reduced rectal volume, no significant difference was observed in DVH parameters. Therefore, it is recommended that adjuvant vaginal cuff HDR brachytherapy should be performed without the use of rifaximin, until further researches’ validate its effects.

The efficacy of antibiotics in reducing morbidity and mortality from heatstroke - A systematic review.

Severe hyperthermia, for example, classical heatstroke or exertional heatstroke from heatwaves or exercise respectively, or from drug ingestion or other non-infective pyrogens, is associated with a high mortality and morbidity, which may be chronic or permanent. Abolition of lipopolysaccharide, from gram-negative intestinal bacteria translocating into the systemic circulation via an intestinal wall rendered permeable from the hyperthermia, reduces the adverse effects, suggesting that antibiotics against the intestinal bacteria may have a similar effect. A systematic review searching Embase, MEDLINE and PubMed from the earliest date available until 2019 was conducted, according to PRISMA guidelines. Two papers were found which fit the criteria. In one, non-absorbable oral antibiotics were administered prior to the onset of heat stress, which reduced the cardiovascular dysfunction and rise in endotoxaemia, but animals succumbed at a lower temperature. In the second, non-absorbable oral antibiotics, in combination with a laxative and enema, given prior to the onset of heat stress, improved mortality; antibiotics administered after the heat stress did not, but the antibiotics used may have limited action against intestinal bacteria. Only two papers were found; both suggest an improvement in organ dysfunction or mortality after an episode of heat stress. No papers were found that investigate the sole use of antibiotics effective against intestinal bacteria given after the onset of heat stress, although biological plausibility suggest they warrant further research.

Longitudinal Changes in the Intestinal Microbiome Composition Following Gut Decontamination in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients: A Pilot Study

Introduction: Early preclinical studies demonstrating that eradication of intestinal bacteria could prevent the development of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) led many adult and pediatric HSCT programs to practice "gut decontamination" (GD) with non-absorbable oral antibiotics for aGVHD prophylaxis. However, there is insufficient data supporting a clear benefit for GD in HSCT patients. Recent adult HSCT studies show that GVHD-related mortality is associated with decreased bacterial diversity in the gut microbiome, suggesting that certain bacterial species are protective against aGVHD. GD may decrease microbiome diversity and lead to worse post-HSCT outcomes. Methods: We conducted a randomized phase 2 study to examine the impact of GD on intestinal microbiome composition in pediatric allogeneic HSCT patients. 20 patients were enrolled and randomized to receive (GD) or not receive (no GD) oral vancomycin-polymyxin per our institutional standard from day -5 through engraftment. Stool samples were collected pre-transplant, weekly until neutrophil engraftment, monthly through day +100, then at 6 months and 1-year post-HSCT. Our primary endpoint is bacterial diversity, quantified by Shannon diversity index, at 2 weeks post-HSCT. Change in diversity is defined as the delta of diversity before transplantation compared to the minimum diversity seen in a single patient in a one-week window (around 14 days post-transplantation). This change in diversity was then averaged (mean) across each treatment arm. The stool microbiome was characterized using shotgun metagenomic sequencing (Nextera Tagmentation and Illumina HiSeq4000 Sequencing) for 10 patients to date, with median count of 1.4x107 reads per sample (range 1.3x106 to 3.3x107). Following quality control (FastQC, Trim Galore, Super Deduper), reads are assigned taxonomic designations using Kraken2 and GenBank (Oct. 2018) database. Secondary endpoints include the frequency of diarrhea (defined as >3 bowel movements per day in the first 7 days post-HSCT), incidence of aGVHD and bacteremia during the first 100 days post-transplant, immune reconstitution, survival, and malignant disease relapse at 2 years after study entry. Comparisons by treatment group were performed with Fisher's exact test (binary) or Wilcoxon rank-sum test (continuous). Results: Baseline patient characteristics were similar between the two arms (Table 1). At present,5 patients (25%) have completed 2 years of follow up, 4 of 15 patients with malignant disease (27%) have had relapse (3 GD, 1 No GD), and 2 patients (10%) in the No GD arm have died (1 malignant relapse, 1 refractory chronic GVHD). Microbiome analysis in the first 10 patients (4 GD, 6 No GD) demonstrates that the average change in Shannon diversity score at 2 weeks is 1.7 (SD 0.86) in GD and 0.65 (SD 0.61) in No GD (Table 2). Diarrhea occurred in 4/10 patients in GD vs 4/10 patients in no GD (p≥0.99).1/10 patients in GD and 3/10 in No GD developed aGVHD grade II or above(p=0.58). Bacteremia within the first 100 days post-HSCT occurred in 1/10 patient in GD, whereas 5/10 patients in No GD had 8 different bacteremia events (p=0.14) (Table 3). Conclusions: This is the first randomized study of gut decontamination in pediatric patients undergoing HSCT with long-term prospective post-transplant stool sample collection and immune monitoring. Though the small sample size is currently not powered to detect differences in clinical outcomes between the 2 study arms, the descriptive microbiome and immune reconstitution data will inform larger studies. There is no statistical difference in the diarrhea, aGVHD, or bacteremia incidence between the two groups but it is interesting that there was 1 vs 8 bacteremia events in GD vs No GD. Microbiota diversity results from our pilot study with 10 patients indicate a trend toward lower diversity at 2 weeks post-transplant in the GD arm. Microbiome analysis of the remaining samples from the remaining 10 patients is underway as well as longitudinal analysis of samples from all patients. Describing the changes to the microbiota composition over time in two groups will provide insight to practice of GD, potential targets for aGVHD, and will provide preliminary data to understand which microbes and microbial gene-pathways may influence immune reconstitution. Disclosures London: United Therapeutics: Consultancy; ArQule, Inc: Consultancy. Ritz:Draper Labs: Consultancy; Kite Pharma: Research Funding; Avrobio: Consultancy; LifeVault Bio: Consultancy; Merck: Research Funding; TScan Therapeutics: Consultancy; Talaris Therapeutics: Consultancy; Celgene: Consultancy; Aleta Biotherapeutics: Consultancy; Equillium: Research Funding. Bhatt:ArcBio: Other: Scientific Advisory Board; January.ai: Other: Scientific Advisory Board; Caribou Bioscience: Other: Scientific Advisory Board; Kaleido Biosciences: Consultancy, Other: Paid Consultant; Janssen Human Microbiome Institute: Consultancy, Other: Paid Consultant; Illumina: Honoraria; 10x Genomics: Other: Research collaboration without funding support; Illumina: Other: Research collaboration without funding support; Agilent: Research Funding; Global Oncology, Inc: Other: Nonprofit Board.

Prophylactic Antibiotics in Cirrhosis: Are They Promoting or Preventing Infections?

Prophylactic Antibiotics in Cirrhosis: Are They Promoting or Preventing Infections?

Routine preoperative mechanical bowel preparation with additive oral antibiotics is associated with a reduced risk of anastomotic leakage in patients undergoing elective oncologic resection for colorectal cancer

BackgroundAnastomotic leakage (AL) following colorectal resection is a serious issue. AL in oncologic patients might negatively affect the overall survival. Recently, mechanical bowel preparation with additive oral antibiotics (MBP + AB) prior to surgery has been suggested as a means of reducing AL. However, it is unclear whether this positive effect is secondary to MBP alone or secondary to the additive oral antibiotic (MBP + AB). The aim of this study was to investigate the effect of mechanical bowel preparation with additive oral antibiotics (MBP + AB) and without additive oral antibiotics (MBP − AB) on the rate of AL following colorectal resection for cancer.Materials and methodsPatients undergoing surgical management for colorectal cancer with anastomosis from January 2014 till September 2017 were included for analysis. Cases undergoing MBP + AB were included in the study group. Patients undergoing MBP − AB were included in the control group. Both groups were compared with regard to the rate of AL.ResultsFour hundred and ninety-six patients: 125 undergoing MBP + AB and 371 undergoing MBP – AB were included for analysis. Significantly, more male patients were included in the MBP – AB group compared to the MBP + AB group: 60.1% vs. 45.6% respectively (p = 0.03). Both groups were similar with regard to age distribution and clinicopathological findings (p > 0.05). The rate of AL was significantly higher in the control group (MBP − AB) compared to study group (MBP + AB) (9.1% vs. 4.0%, p = 0.03).ConclusionMechanical bowel preparation with additive oral antibiotics prior to elective colorectal resection with anastomosis significantly reduces the risk of AL. Therefore, mechanical bowel preparation with additive non-absorbable oral antibiotics should be recommended in all cases prior to elective colorectal surgery.

Novel perspectives in the management of decompensated cirrhosis.

The current approaches to the management of patients with decompensated cirrhosis are based on targeted strategies aimed at preventing or treating specific complications of the disease. The improved knowledge of the pathophysiological background of advanced cirrhosis, represented by a sustained systemic inflammation strictly linked to a circulatory dysfunction, provides a novel paradigm for the management of these patients, with the ambitious target of modifying the course of the disease by preventing the onset of complications and multiorgan failure; these interventions will eventually improve patients' quality of life, prolong survival and reduce health-care costs. Besides aetiological treatments, these goals could be achieved by persistently antagonizing key pathophysiological events, such as portal hypertension, abnormal bacterial translocation from the gut, liver damage, systemic inflammation, circulatory dysfunction and altered immunological responses. Interestingly, in addition to strategies based on new therapeutic agents, these targets can be tackled by employing drugs that are already used in patients with cirrhosis for different indications or in other clinical settings, including non-absorbable oral antibiotics, non-selective β-blockers, human albumin and statins. The scope of the present Review includes reporting updated information on the treatments that promise to influence the course of advanced cirrhosis and thus act as disease-modifying agents.

Current Trends in the Use of Bowel Preparation for Colorectal Surgery

This article reviews recent findings in the use of bowel preparation for preventing infectious complications after colorectal surgery. Whereas mechanical bowel preparation (MBP) was formerly used routinely in combination with prophylactic non-absorbable oral antibiotics (OAs) and prophylactic intravenous antibiotics, there was a trend toward omitting OAs in the 1990s and early 2000s. Since the mid-2000s, the use of MBP has declined given evidence of the limited role of MBP alone in preventing infectious complications. However, recent studies have demonstrated favorable outcomes after MBP when used in combination with OAs. Results from recent studies have prompted surgeons to reexamine the appropriate regimen for preoperative bowel preparation. The principal question that should now be addressed by future research is whether OAs alone reduce surgical infectious complications after colorectal surgery.

Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study

BackgroundAutism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.ResultsMTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).ConclusionsThis exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.Trial registrationThis trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554

Antibiotic-mediated modification of the intestinal microbiome in allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many patients with severe benign and malignant hematologic disorders. The success of allogeneic HSCT is limited by the development of transplant-related complications such as acute graft-versus-host disease (GvHD). Early pre-clinical studies suggested that intestinal microflora contribute to the pathogenesis of acute GvHD, and that growth suppression or eradication of intestinal bacteria prevented the development of acute GvHD even in MHC-mismatched transplants. These observations led to the practice of gut decontamination (GD) with oral non-absorbable antibiotics in patients undergoing allogeneic HSCT as a method of acute GvHD prophylaxis. Microbiome studies in the modern sequencing era are beginning to challenge the benefit of this practice. In this review, we provide a historical perspective on the practice of GD and highlight findings from the limited number of clinical trials evaluating the use of GD for acute GvHD prevention in allogeneic HSCT patients. In addition, we examine the role of the gut microbiota in allogeneic HSCT in the context of recent studies linking the microflora to regulation of intestinal immune homeostasis. We discuss the implications of these findings for future strategies to reduce acute GvHD risk by selective manipulation of the microbiota.

Quantification of Rifaximin in Tablets by Spectrophotometric Method Ecofriendly in Ultraviolet Region.

Rifaximin is an oral nonabsorbable antibiotic that acts locally in the gastrointestinal tract with minimal systemic adverse effects. It does not have spectrophotometric method ecofriendly in the ultraviolet region described in official compendiums and literature. The analytical techniques for determination of rifaximin reported in the literature require large amount of time to release results and are significantly onerous. Furthermore, they use toxic reagents both for the operator and environment and, therefore, cannot be considered environmentally friendly analytical techniques. The objective of this study was to develop and validate an ecofriendly spectrophotometric method in the ultraviolet region to quantify rifaximin in tablets. The method was validated, showing linearity, selectivity, precision, accuracy, and robustness. It was linear over the concentration range of 10–30 mg L−1 with correlation coefficients greater than 0.9999 and limits of detection and quantification of 1.39 and 4.22 mg L−1, respectively. The validated method is useful and applied for the routine quality control of rifaximin, since it is simple with inexpensive conditions and fast in the release of results, optimizes analysts and equipment, and uses environmentally friendly solvents, being considered a green method, which does not prejudice either the operator or the environment.

Rifaximin combined with polymyxins: A potential regimen for selective decontamination of multidrug-resistant bacteria in the digestive tract?

Selective decontamination of the digestive tract (SDD) using combinations of oral non-absorbable antibiotics has been proposed as a means of preventing multidrug-resistant (MDR) infections. The minimum inhibitory concentrations (MICs) of rifaximin (RIFAX) were determined against 262 Gram-negative and Gram-positive bacterial isolates by broth microtitre assay. Rifampicin (RIF) was used as a comparator in the analysis. Synergistic interactions between RIFAX and polymyxin B (PMB) were assessed by using the chequerboard method and calculating the fractional inhibitory concentration index (FICI). The antimicrobial activities of both RIFAX and RIF were similar with little variation in the overall MIC distributions for Gram-negative non-fermenters and Gram-positive bacteria. However, against Enterobacteriaceae higher MICs (>16mg/L) were observed for RIFAX than for RIF (50% vs 27%). Amongst the 262 isolates tested, 100 could be considered resistant to RIFAX. Overall, the combination of RIFAX and PMB was more active against all of the isolates tested compared with either drug alone, with reductions of 2-11 doubling dilutions in individual MICs. Potent synergy was observed with the RIFAX+PMB combination using FICI criteria (FICI range 0.02-0.5). The data presented here suggest that combination therapy may be significantly more effective against isolates with RIFAX and/or PMB resistance and could be considered as part of a SDD regimen aimed at reducing enteric carriage of MDR pathogens in colonised and infected patients.