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Qiao W, Wang L, Luo Y, Yang T. Synthetic approaches and therapeutic applications of FDA-approved antibacterial agents: A comprehensive review from 2003 to 2023. Eur J Med Chem 2025; 285:117267. [PMID: 39808973 DOI: 10.1016/j.ejmech.2025.117267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/16/2024] [Accepted: 01/08/2025] [Indexed: 01/16/2025]
Abstract
The increasing threat of antibiotic resistance has necessitated the development of new antibacterial agents. 33 novel antibacterial agents have been approved by the U.S. Food and Drug Administration (FDA) within the two-decade timeframe from 2003 to 2023. These novel antibacterial agents included new chemical classes, such as lipopeptides, 18-membered macrolides, diaromatic quinolones, and nitroimidazoles, as well as modified existing classes, such as quinolones, tetracyclines, β-lactams, macrolides, oxazolidinones, and aminoglycosides. Nonetheless, during these twenty years, approval for new antibiotics was notably absent in 6 different years, and the total number of antibiotics approved was considerably less than that of other drug classes, including anticancer drugs. In this review, we provide an extensive analysis of the synthetic approaches and therapeutic applications of these approved antibacterial agents. We believe that this review will help further research on potential antibacterial agents for clinical use and development of next generation of antibacterial agents.
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Affiliation(s)
- Wenliang Qiao
- Lung Cancer Center, Laboratory of Lung Cancer, and Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lijiao Wang
- College of Food and Bioengineering, Xihua University, Sichuan, 610039, China
| | - Youfu Luo
- Lung Cancer Center, Laboratory of Lung Cancer, and Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, 610041, China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tao Yang
- Lung Cancer Center, Laboratory of Lung Cancer, and Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, Chengdu, 610041, China; Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Huang C, Lan H, Bai M, Chen J, Xu S, Sun Q, Chen Q, Mao W, Jiang J, Zhu J. Rifaximin alleviates irinotecan-induced diarrhea in mice model. Ann Med 2024; 56:2429029. [PMID: 39575573 PMCID: PMC11587719 DOI: 10.1080/07853890.2024.2429029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 04/04/2024] [Accepted: 04/12/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND Irinotecan is a chemotherapeutic drug widely used to treat solid tumors. However, its effectiveness is limited by the severely delayed onset of diarrhea. This study aimed to confirm the protective effects of the non-systemic oral antibiotic rifaximin on irinotecan-induced mucositis in mice model. MATERIALS AND METHODS Six to eight week-old BALB/c mice were treated with saline, irinotecan (50 mg/kg, i.p. once daily), rifaximin (50 mg/kg, p.o. twice daily), or irinotecan + rifaximin for 9 consecutive days. Signs of diarrhea, bloody diarrhea, and body weight were monitored daily. Intestinal tissues were harvested for histopathological analysis and quantitative PCR. SN38 and SN38G concentration in intestine were detected using LC-MS analysis. Intestinal bacteria β-glucuronidase (BGUS) activity was detected using mouse feces. We performed 16S rRNA sequencing to investigate the gut microbiota composition. Gut permeability was tested in vivo by measuring the fluorescein isothiocyanate-dextran intensity in the serum. RESULTS Rifaximin reduced the frequency of delayed diarrhea and attenuated the severity of diarrhea caused by irinotecan in mice. Rifaximin significantly inhibited SN38 exposure in intestine and irinotecan-induced increase in BGUS activity. Rifaximin alleviated intestinal mucosal inflammation, prevented intestinal epithelial damage caused by irinotecan, and maintained gut barrier function. Moreover, the consecutive use of rifaximin did not cause a disorder in gut microbiota and reduced irinotecan-induced Firmicutes expansion. More importantly, rifaximin inhibited the expansion of some microbiota (such as Blautia, Eggerthella, and f_Enterobacteriaceae) and promoted an increase in beneficial microbiota (such as Lactobacillus intestinalis, Lachnospiraceae NK4A136 group, and f_Oscillospiraceae). CONCLUSIONS Preventive use of rifaximin is a feasible method to protect against irinotecan-induced diarrhea.
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Affiliation(s)
- Chengyi Huang
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Huiyin Lan
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Minghua Bai
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Jinggang Chen
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Shengkun Xu
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Quanquan Sun
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Qianping Chen
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Wei Mao
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Jin Jiang
- Department of Oncology, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Ji Zhu
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
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Yang W, Guo G, Sun C. Therapeutic potential of rifaximin in liver diseases. Biomed Pharmacother 2024; 178:117283. [PMID: 39126775 DOI: 10.1016/j.biopha.2024.117283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/05/2024] [Accepted: 08/08/2024] [Indexed: 08/12/2024] Open
Abstract
Rifaximin, derived from rifamycin, is a broad-spectrum antibiotic by inhibiting bacterial RNA synthesis. Rifaximin has a very low intestinal absorption and exerts its antimicrobial activity primarily in the intestinal tract. It regulates the gut microbiota with limited side effects systemically. Rifaximin has been recommended for the treatment of hepatic encephalopathy but some studies shed light on its medicinal effects in many other diseases. For instance, rifaximin may suppress the progression of liver fibrosis and its related complications, and ameliorate metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, etc. Rifaximin can also mediate anti-inflammation, antiproliferation, and proapoptotic events by activating pregnane X receptor, which is efficious in cancers such as colon cancer. In addition, some investigations have shown rifaximin may play a therapeutic role in various autoimmune and neurological disorders. However, these findings still need more real-world practices and in-depth investigations to obtain more precise indications and fully elucidate the multifaceted potentials of rifaximin.
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Affiliation(s)
- Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin 300308, China
| | - Gaoyue Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin 300308, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin 300308, China.
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Guevara-Cruz M, Hernández-Gómez KG, Condado-Huerta C, González-Salazar LE, Peña-Flores AK, Pichardo-Ontiveros E, Serralde-Zúñiga AE, Sánchez-Tapia M, Maya O, Medina-Vera I, Noriega LG, López-Barradas A, Rodríguez-Lima O, Mata I, Olin-Sandoval V, Torres N, Tovar AR, Velázquez-Villegas LA. Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial. Clin Nutr 2024; 43:1914-1928. [PMID: 39003957 DOI: 10.1016/j.clnu.2024.06.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 06/24/2024] [Accepted: 06/30/2024] [Indexed: 07/16/2024]
Abstract
BACKGROUND Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota. METHODS AND FINDINGS A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n2p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of Phascolarctobacterium faecium (p = 0.019) in the CR group and Ruminococcus bromii (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study. CONCLUSIONS We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials. TRIAL REGISTRATION This trial was registered with ClinicalTrials.gov (NCT05200468).
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Affiliation(s)
- Martha Guevara-Cruz
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Karla G Hernández-Gómez
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Citlally Condado-Huerta
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Luis E González-Salazar
- Servicio de Nutriología Clínica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Ana Karen Peña-Flores
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Edgar Pichardo-Ontiveros
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Aurora E Serralde-Zúñiga
- Servicio de Nutriología Clínica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Mónica Sánchez-Tapia
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Otoniel Maya
- Chalmers e-Commons. Chalmers University of Technology, Gotemburg, Vastra Gotaland, Sweden
| | - Isabel Medina-Vera
- Departamento de Metodología de la Investigación, Instituto Nacional de Pediatría, Ciudad de México, Mexico
| | - Lilia G Noriega
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Adriana López-Barradas
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Oscar Rodríguez-Lima
- Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Irma Mata
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Viridiana Olin-Sandoval
- Laboratorio 43. Departamento de Biotecnología y Bioingeniería, Cinvestav-Zacatenco, Ciudad de México, Mexico
| | - Nimbe Torres
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Armando R Tovar
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Laura A Velázquez-Villegas
- Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico.
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Kebede V, Ravizza T, Balosso S, Di Sapia R, Canali L, Soldi S, Galletti S, Papazlatani C, Karas PA, Vasileiadis S, Sforzini A, Pasetto L, Bonetto V, Vezzani A, Vesci L. Early treatment with rifaximin during epileptogenesis reverses gut alterations and reduces seizure duration in a mouse model of acquired epilepsy. Brain Behav Immun 2024; 119:363-380. [PMID: 38608741 DOI: 10.1016/j.bbi.2024.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 04/04/2024] [Accepted: 04/09/2024] [Indexed: 04/14/2024] Open
Abstract
The gut microbiota is altered in epilepsy and is emerging as a potential target for new therapies. We studied the effects of rifaximin, a gastrointestinal tract-specific antibiotic, on seizures and neuropathology and on alterations in the gut and its microbiota in a mouse model of temporal lobe epilepsy (TLE). Epilepsy was induced by intra-amygdala kainate injection causing status epilepticus (SE) in C57Bl6 adult male mice. Sham mice were injected with vehicle. Two cohorts of SE mice were fed a rifaximin-supplemented diet for 21 days, starting either at 24 h post-SE (early disease stage) or at day 51 post-SE (chronic disease stage). Corresponding groups of SE mice (one each disease stage) were fed a standard (control) diet. Cortical ECoG recording was done at each disease stage (24/7) for 21 days in all SE mice to measure the number and duration of spontaneous seizures during either rifaximin treatment or control diet. Then, epileptic mice ± rifaximin and respective sham mice were sacrificed and brain, gut and feces collected. Biospecimens were used for: (i) quantitative histological analysis of the gut structural and cellular components; (ii) markers of gut inflammation and intestinal barrier integrity by RTqPCR; (iii) 16S rRNA metagenomics analysis in feces. Hippocampal neuronal cell loss was assessed in epileptic mice killed in the early disease phase. Rifaximin administered for 21 days post-SE (early disease stage) reduced seizure duration (p < 0.01) and prevented hilar mossy cells loss in the hippocampus compared to epileptic mice fed a control diet. Epileptic mice fed a control diet showed a reduction of both villus height and villus height/crypt depth ratio (p < 0.01) and a decreased number of goblet cells (p < 0.01) in the duodenum, as well as increased macrophage (Iba1)-immunostaining in the jejunum (p < 0.05), compared to respective sham mice. Rifaximin's effect on seizures was associated with a reversal of gut structural and cellular changes, except for goblet cells which remained reduced. Seizure duration in epileptic mice was negatively correlated with the number of mossy cells (p < 0.01) and with villus height/crypt depth ratio (p < 0.05). Rifaximin-treated epileptic mice also showed increased tight junctions (occludin and ZO-1, p < 0.01) and decreased TNF mRNA expression (p < 0.01) in the duodenum compared to epileptic mice fed a control diet. Rifaximin administered for 21 days in chronic epileptic mice (chronic disease stage) did not change the number or duration of seizures compared to epileptic mice fed a control diet. Chronic epileptic mice fed a control diet showed an increased crypt depth (p < 0.05) and reduced villus height/crypt depth ratio (p < 0.01) compared to respective sham mice. Rifaximin treatment did not affect these intestinal changes. At both disease stages, rifaximin modified α- and β-diversity in epileptic and sham mice compared to respective mice fed a control diet. The microbiota composition in epileptic mice, as well as the effects of rifaximin at the phylum, family and genus levels, depended on the stage of the disease. During the early disease phase, the abundance of specific taxa was positively correlated with seizure duration in epileptic mice. In conclusion, gut-related alterations reflecting a dysfunctional state, occur during epilepsy development in a TLE mouse model. A short-term treatment with rifaximin during the early phase of the disease, reduced seizure duration and neuropathology, and reversed some intestinal changes, strengthening the therapeutic effects of gut-based therapies in epilepsy.
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Affiliation(s)
- Valentina Kebede
- Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
| | - Teresa Ravizza
- Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
| | - Silvia Balosso
- Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
| | - Rossella Di Sapia
- Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
| | - Luca Canali
- Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
| | - Sara Soldi
- AAT Advanced Analytical Technologies Srl, Fiorenzuola d'Arda (PC), Italy
| | - Serena Galletti
- AAT Advanced Analytical Technologies Srl, Fiorenzuola d'Arda (PC), Italy
| | - Christina Papazlatani
- Dept. Biochemistry and Biotechnology University of Thessaly Biopolis, Larissa, Greece
| | - Panagiotis A Karas
- Dept. Biochemistry and Biotechnology University of Thessaly Biopolis, Larissa, Greece
| | - Sotirios Vasileiadis
- Dept. Biochemistry and Biotechnology University of Thessaly Biopolis, Larissa, Greece
| | | | - Laura Pasetto
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
| | - Valentina Bonetto
- Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
| | - Annamaria Vezzani
- Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
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Abstract
Chronic liver disease (CLD) is a persistent public health burden, with over one billion cases reported worldwide. In most cases, the progression of CLD is slow and undulating with end-stage liver disease developing at variable time points depending on the underlying etiology of the disease. The concept of reversibility or halting progression to end stage liver disease is recent and various medications are in the pipeline which influence the progression of CLD. Non-invasive tests for monitoring of CLD may have the potential to avoid the morbidity and mortality related to invasive procedures. However, their applicability and validation in pediatrics requires further development and a coordinated effort by large pediatric liver centres. Recent advances in metabolomics and modern molecular technologies have led to an understanding of the interaction between gut microbiome liver axis and gut dysbiosis contributing to liver diseases. In the future, modifying the gut microbiome has the potential to change the outcome and significantly reduce the morbidity associated with CLD. This article focuses on newer modalities and concepts in the management of CLD, which may help develop strategies to prevent its progression to end-stage liver disease and associated morbidity/mortality.
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Affiliation(s)
- Ezyana Effandie
- Liver Unit (Including Small Bowel Transplantation), Birmingham Women's and Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK
| | - Girish L Gupte
- Liver Unit (Including Small Bowel Transplantation), Birmingham Women's and Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.
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Yoon SH, Yang IJ, Kim JY, Lee KH. Efficacy of a 1 day Rifaximin and Metronidazole Regimen and Mechanical Bowel Preparation for Preventing Surgical Site Infection in Minimally Invasive Colorectal Cancer Surgery: A Prospective Observational Study. Am Surg 2024; 90:550-559. [PMID: 37707885 DOI: 10.1177/00031348231200667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023]
Abstract
BACKGROUND A combination of oral antibiotics and mechanical bowel preparation is recommended for patients scheduled to undergo elective colorectal surgery on the basis of recent large trials that have reported the superiority of this approach in preventing surgical site infections (SSIs). However, there are no standard recommendations for this approach. Therefore, in this study, we evaluated the efficacy of rifaximin and metronidazole and mechanical bowel preparation for preventing SSIs in cases of minimally invasive surgery for colorectal cancer. METHODS This single-arm prospective observational study included 256 individuals. The primary end point was the rate of SSI. Rifaximin 400 mg and metronidazole 500 mg were administered twice daily (10 am and 10 pm), and mechanical bowel preparation was administered the day before the operation. RESULTS After excluding 15 patients, 241 were enrolled. No adverse event occurred following the administration of oral antibiotics and mechanical bowel preparation; there was 100% compliance. The total SSI rate was 2.9%; the rates of incisional and organ/space SSIs were 1.2% and 1.7%, respectively. All patients were treated conservatively. Univariate analyses revealed preoperative anemia, hypoalbuminemia, and transfusion and postoperative transfusion were significantly associated with SSIs. DISCUSSION A 1 day rifaximin and metronidazole regimen with mechanical bowel preparation for elective minimally invasive surgery for colorectal cancer was associated with a favorable SSI rate of 2.9%, safety, and high compliance. This approach is appropriate for inclusion in the current guidelines for perioperative management of patients scheduled to undergo minimally invasive surgery for colorectal cancer.
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Affiliation(s)
- Seung-Hwan Yoon
- Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - In Jun Yang
- Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Ji Yeon Kim
- Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Kyung-Ha Lee
- Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
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Piccin A, Gulotta M, di Bella S, Martingano P, Crocè LS, Giuffrè M. Diverticular Disease and Rifaximin: An Evidence-Based Review. Antibiotics (Basel) 2023; 12:antibiotics12030443. [PMID: 36978310 PMCID: PMC10044695 DOI: 10.3390/antibiotics12030443] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/20/2023] [Accepted: 02/21/2023] [Indexed: 02/25/2023] Open
Abstract
There have been considerable advances in the treatment of diverticular disease in recent years. Antibiotics are frequently used to treat symptoms and prevent complications. Rifaximin, a non-absorbable antibiotic, is a common therapeutic choice for symptomatic diverticular disease in various countries, including Italy. Because of its low systemic absorption and high concentration in stools, it is an excellent medicine for targeting the gastrointestinal tract, where it has a beneficial effect in addition to its antibacterial properties. Current evidence shows that cyclical rifaximin usage in conjunction with a high-fiber diet is safe and effective for treating symptomatic uncomplicated diverticular disease, while the cost-effectiveness of long-term treatment is unknown. The use of rifaximin to prevent recurrent diverticulitis is promising, but further studies are needed to confirm its therapeutic benefit. Unfortunately, there is no available evidence on the efficacy of rifaximin treatment for acute uncomplicated diverticulitis.
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Affiliation(s)
- Anna Piccin
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
| | - Marco Gulotta
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
| | - Stefano di Bella
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
- Infectious Disease Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), 34128 Trieste, Italy
| | - Paola Martingano
- Department of Radiology, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), 34128 Trieste, Italy
| | - Lory Saveria Crocè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
- Liver Clinic, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), 34128 Trieste, Italy
| | - Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy
- Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT 06510, USA
- Correspondence:
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Hong CT, Chan L, Chen KY, Lee HH, Huang LK, Yang YCSH, Liu YR, Hu CJ. Rifaximin Modifies Gut Microbiota and Attenuates Inflammation in Parkinson's Disease: Preclinical and Clinical Studies. Cells 2022; 11:3468. [PMID: 36359864 PMCID: PMC9656351 DOI: 10.3390/cells11213468] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/30/2022] [Accepted: 10/27/2022] [Indexed: 09/15/2023] Open
Abstract
Patients with Parkinson's disease (PD) exhibit distinct gut microbiota, which may promote gut-derived inflammation. Rifaximin is a nonabsorbable antibiotic that can modify gut microbiota. The present study investigated the effect of rifaximin on gut microbiota and inflammation status in PD. The study examined the effect of long-term rifaximin treatment on in vivo transgenic PD mice (MitoPark) and short-term rifaximin treatment on patients with PD. Rifaximin treatment caused a significant change in gut microbiota in the transgenic PD mice; in particular, it reduced the relative abundance of Prevotellaceae UCG-001 and increased the relative abundance of Bacteroides, Muribaculum, and Lachnospiraceae UCG-001. Rifaximin treatment attenuated serum interleukin-1β, interleukin-6 and tumor necrosis factor-α, claudin-5 and occludin, which indicated the reduction of systemic inflammation and the protection of the blood-brain barrier integrity. The rifaximin-treated MitoPark mice exhibited better motor and memory performance than did the control mice, with lower microglial activation and increased neuronal survival in the hippocampus. In the patients with PD, 7-day rifaximin treatment caused an increase in the relative abundance of Flavonifractor 6 months after treatment, and the change in plasma proinflammatory cytokine levels was negatively associated with the baseline plasma interleukin-1α level. In conclusion, the present study demonstrated that rifaximin exerted a neuroprotective effect on the transgenic PD mice by modulating gut microbiota. We observed that patients with higher baseline inflammation possibly benefited from rifaximin treatment. With consideration for the tolerability and safety of rifaximin, randomized controlled trials should investigate the disease-modification effect of long-term treatment on select patients with PD.
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Affiliation(s)
- Chien-Tai Hong
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Lung Chan
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Kai-Yun Chen
- Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Hsun-Hua Lee
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Li-Kai Huang
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
| | - Yu-Chen S. H. Yang
- Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, Taiwan
| | - Yun-Ru Liu
- Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, Taiwan
| | - Chaur-Jong Hu
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
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10
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The Relevance of Crystal Forms in the Pharmaceutical Field: Sword of Damocles or Innovation Tools? Int J Mol Sci 2022; 23:ijms23169013. [PMID: 36012275 PMCID: PMC9408954 DOI: 10.3390/ijms23169013] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/01/2022] [Accepted: 08/05/2022] [Indexed: 12/22/2022] Open
Abstract
This review is aimed to provide to an “educated but non-expert” readership and an overview of the scientific, commercial, and ethical importance of investigating the crystalline forms (polymorphs, hydrates, and co-crystals) of active pharmaceutical ingredients (API). The existence of multiple crystal forms of an API is relevant not only for the selection of the best solid material to carry through the various stages of drug development, including the choice of dosage and of excipients suitable for drug development and marketing, but also in terms of intellectual property protection and/or extension. This is because the physico-chemical properties, such as solubility, dissolution rate, thermal stability, processability, etc., of the solid API may depend, sometimes dramatically, on the crystal form, with important implications on the drug’s ultimate efficacy. This review will recount how the scientific community and the pharmaceutical industry learned from the catastrophic consequences of the appearance of new, more stable, and unsuspected crystal forms. The relevant aspects of hydrates, the most common pharmaceutical solid solvates, and of co-crystals, the association of two or more solid components in the same crystalline materials, will also be discussed. Examples will be provided of how to tackle multiple crystal forms with screening protocols and theoretical approaches, and ultimately how to turn into discovery and innovation the purposed preparation of new crystalline forms of an API.
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11
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Santopaolo F, Coppola G, Giuli L, Gasbarrini A, Ponziani FR. Influence of Gut–Liver Axis on Portal Hypertension in Advanced Chronic Liver Disease: The Gut Microbiome as a New Protagonist in Therapeutic Management. MICROBIOLOGY RESEARCH 2022; 13:539-555. [DOI: 10.3390/microbiolres13030038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Clinically significant portal hypertension is associated with most complications of advanced chronic liver disease (ACLD), including variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. Gut dysbiosis is a hallmark of ACLD with portal hypertension and consists of the overgrowth of potentially pathogenic bacteria and a decrease in autochthonous bacteria; additionally, congestion makes the intestinal barrier more permeable to bacteria and their products, which contributes to the development of complications through inflammatory mechanisms. This review summarizes current knowledge on the role of the gut–liver axis in the pathogenesis of portal hypertension, with a focus on therapies targeting portal hypertension and the gut microbiota. The modulation of the gut microbiota on several levels represents a major challenge in the upcoming years; in-depth characterization of the molecular and microbiological mechanisms linking the gut–liver axis to portal hypertension in a bidirectional relationship could pave the way to the identification of new therapeutic targets for innovative therapies in the management of ACLD.
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Affiliation(s)
- Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Gaetano Coppola
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Lucia Giuli
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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12
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Mitochondrial Side Effects of Surgical Prophylactic Antibiotics Ceftriaxone and Rifaximin Lead to Bowel Mucosal Damage. Int J Mol Sci 2022; 23:ijms23095064. [PMID: 35563455 PMCID: PMC9103148 DOI: 10.3390/ijms23095064] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/28/2022] [Accepted: 04/30/2022] [Indexed: 02/04/2023] Open
Abstract
Despite their clinical effectiveness, a growing body of evidence has shown that many classes of antibiotics lead to mitochondrial dysfunction. Ceftriaxone and Rifaximin are first choice perioperative antibiotics in gastrointestinal surgery targeting fundamental processes of intestinal bacteria; however, may also have negative consequences for the host cells. In this study, we investigated their direct effect on mitochondrial functions in vitro, together with their impact on ileum, colon and liver tissue. Additionally, their impact on the gastrointestinal microbiome was studied in vivo, in a rat model. Rifaximin significantly impaired the oxidative phosphorylation capacity (OxPhos) and leak respiration in the ileal mucosa, in line with increased oxidative tissue damage and histological changes following treatment. Ceftriaxone prophylaxis led to similar changes in the colon mucosa. The composition and diversity of bacterial communities differed extensively in response to antibiotic pre-treatment. However, the relative abundances of the toxin producing species were not increased. We have confirmed the harmful effects of prophylactic doses of Rifaximin and Ceftriaxone on the intestinal mucosa and that these effects were related to the mitochondrial dysfunction. These experiments raise awareness of mitochondrial side effects of these antibiotics that may be of clinical importance when evaluating their adverse effects on bowel mucosa.
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13
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Jiménez C, Ventura-Cots M, Sala M, Calafat M, Garcia-Retortillo M, Cirera I, Cañete N, Soriano G, Poca M, Simón-Talero M, Altamirano J, Lucey M, Garcia-Tsao G, Brown RS, Schwabe RF, Verna EC, Schnabl B, Bosques-Padilla F, Mathurin P, Caballería J, Louvet A, Shawcross DL, Abraldes JG, Genescà J, Bataller R, Vargas V. Effect of rifaximin on infections, acute-on-chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA-AH). Liver Int 2022; 42:1109-1120. [PMID: 35220659 PMCID: PMC9311407 DOI: 10.1111/liv.15207] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 01/31/2022] [Accepted: 02/15/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND & AIMS Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort. METHODS This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end-stage liver disease (MELD). We evaluated bacterial infections, liver-related complications, mortality and liver function tests after 90 days. RESULTS Twenty-one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute-on-chronic liver failure (ACLF) linked to infections within the treatment group. Liver-related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment. CONCLUSIONS Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.
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Affiliation(s)
- César Jiménez
- Vall d'Hebron Hospital Universitari, Liver Unit; Vall d'Hebron Institut de Recerca, Liver Unit, Universitat Autonoma de Barcelona, Department of Medicine, Barcelona, Spain
| | - Meritxell Ventura-Cots
- Vall d'Hebron Hospital Universitari, Liver Unit; Vall d'Hebron Institut de Recerca, Liver Unit, Universitat Autonoma de Barcelona, Department of Medicine, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Center for Liver Diseases, Pittsburgh Liver Research Center, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Margarita Sala
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Gastroenterology Department, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
| | - Margalida Calafat
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Gastroenterology Department, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
| | - Montserrat Garcia-Retortillo
- Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Isabel Cirera
- Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Nuria Cañete
- Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Germán Soriano
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Department of Gastroenterology Hospital de la Santa Creu i Sant Pau Barcelona Spain, Institut d'Investigació Biomèdica Sant Pau IIB Sant Pau, Gastroenterology, Barcelona, Catalunya, ES, Universitat Autonoma de Barcelona, Medicine, Barcelona, Catalunya, Spain
| | - María Poca
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Department of Gastroenterology Hospital de la Santa Creu i Sant Pau Barcelona Spain, Institut d'Investigació Biomèdica Sant Pau IIB Sant Pau, Gastroenterology, Barcelona, Catalunya, ES, Universitat Autonoma de Barcelona, Medicine, Barcelona, Catalunya, Spain
| | - Macarena Simón-Talero
- Vall d'Hebron Hospital Universitari, Liver Unit; Vall d'Hebron Institut de Recerca, Liver Unit, Universitat Autonoma de Barcelona, Department of Medicine, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - José Altamirano
- Department of Internal Medicine, Hospital Quironsalud, Barcelona, Spain
| | - Michael Lucey
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Guadalupe Garcia-Tsao
- Section of Digestive Diseases, Yale University, New Haven, Connecticut Section of Digestive Diseases, Department of Veterans Affairs Connecticut Healthcare, West Haven, Connecticut, USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York City, New York, USA
| | - Robert F Schwabe
- Department of Medicine, Columbia University, New York City, New York, USA
| | - Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York City, New York, USA
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | | | - Philippe Mathurin
- Service des Maladies de L'appareil Digestif et Unité INSERM U995, Lille, France
| | - Juan Caballería
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Liver Unit, Hospital Clinic, Barcelona, Spain
| | - Alexandre Louvet
- Service des Maladies de L'appareil Digestif et Unité INSERM U995, Lille, France
| | - Debbie L Shawcross
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, Institute of Liver Sciences, King's College London, London, UK
| | - Juan G Abraldes
- Division of Gastroenterology, Liver Unit, University of Alberta, Edmonton, Canada
| | - Joan Genescà
- Vall d'Hebron Hospital Universitari, Liver Unit; Vall d'Hebron Institut de Recerca, Liver Unit, Universitat Autonoma de Barcelona, Department of Medicine, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Ramon Bataller
- Center for Liver Diseases, Pittsburgh Liver Research Center, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Víctor Vargas
- Vall d'Hebron Hospital Universitari, Liver Unit; Vall d'Hebron Institut de Recerca, Liver Unit, Universitat Autonoma de Barcelona, Department of Medicine, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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14
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Nathwani R, Mullish B, Kockerling D, Cole A, Selvapatt N, Dhar A. Review of Rifaximin: A Summary of the Current Evidence and Benefits Beyond Licensed Use. EUROPEAN MEDICAL JOURNAL 2021. [DOI: 10.33590/emj/21-00026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Antibiotic resistance in patients with cirrhosis continues to draw significant attention. With a propensity to frequent hospitalisations, patients with cirrhosis are subject to frequent antibiotic prescription. This increases their risk of developing resistance to one or more antimicrobial agents, making management of their condition particularly challenging. Despite advancements being made in the management of liver disease, mortality rates continue to rise: almost 5-fold in those <65 years of age while remaining the leading cause of death in those 35–49 years of age. Alternative therapeutic options to prevent disease progression and cirrhosis-associated complications are urgently required; rifaximin is one such example. The medication use in patients with cirrhosis demonstrates additional benefits beyond current licensed use in the UK, that being for the prevention of hepatic encephalopathy and traveller’s diarrhoea; rifaximin has especially been explored beyond current licensed use in the context of enteric-driven pathologies. Through the therapy’s key central action as a broad-spectrum antimicrobial, rifaximin has the ability to modulate the gut–liver axis via removal of gut microbial products associated with the progression of cirrhosis and its sequalae.
The benefits of rifaximin use continues to gather momentum, given its non-absorbable nature and well-tolerated side-effect profile, and these require consideration. With broad-spectrum antimicrobial properties, its use may assist in overcoming the conundrum posed of antibiotic resistance amongst patients with cirrhosis. This literature review discusses the chemical and antimicrobial properties of rifaximin, its licenced indication for use, and its reported benefits beyond this, as well as concerns regarding rifaximin resistance.
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Affiliation(s)
- Rooshi Nathwani
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
| | - Benjamin Mullish
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
| | - David Kockerling
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
| | - Alexander Cole
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
| | - Nowlan Selvapatt
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
| | - Ameet Dhar
- Liver Unit/Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
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15
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Shmoylova YY, Kovygin YA, Ledenyova IV, Prezent MA, Baranin SV, Shikhaliev KS. Synthesis of new tetrahydropyrido[1,2-a]benzimidazoles based on recyclization of N-arylitaconimides with 2-cyanomethylbenzimidazole. MENDELEEV COMMUNICATIONS 2021. [DOI: 10.1016/j.mencom.2021.03.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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16
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Novel therapeutics for portal hypertension and fibrosis in chronic liver disease. Pharmacol Ther 2020; 215:107626. [DOI: 10.1016/j.pharmthera.2020.107626] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 06/30/2020] [Indexed: 02/06/2023]
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17
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Lee SD, Singla A, Rulyak SJ, Clark‐Snustad K. Double‐blind, randomised, placebo‐controlled crossover trial to evaluate the clinical efficacy of rifaximin in patients with moderate to severe active Crohn’s disease. ACTA ACUST UNITED AC 2020. [DOI: 10.1002/ygh2.416] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Scott D. Lee
- University of Washington School of Medicine Seattle WA USA
| | - Anand Singla
- University of Washington School of Medicine Seattle WA USA
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18
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Lv XY, Ding HG, Zheng JF, Fan CL, Li L. Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study. World J Gastroenterol 2020; 26:199-218. [PMID: 31988585 PMCID: PMC6962437 DOI: 10.3748/wjg.v26.i2.199] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 12/06/2019] [Accepted: 12/21/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis. However, few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites. AIM To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism. METHODS A total of 75 cirrhotic patients with refractory ascites were enrolled in the study (50 in a rifaximin and 25 in a control group). Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics (19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics). All patients received conventional treatment for refractory ascites, while patients in the rifaximin group received oral rifaximin-α 200 mg four times daily for at least 2 wk. The ascites grade, fasting weight, liver and kidney function, and inflammatory factors in the plasma were evaluated before and after treatment. In addition, the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment. The patients were followed for 6 mo. RESULTS Compared with the control group, the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin (P = 0.011 and 0.009, respectively). The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group (P = 0.048). The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group (P = 0.024). The abundance of Roseburia, Haemophilus, and Prevotella was significantly reduced after rifaximin treatment, while the abundance of Lachnospiraceae_noname, Subdoligranulum, and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics. The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics. CONCLUSION Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites. A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria, thus improving the systemic inflammatory state.
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Affiliation(s)
- Xin-Yue Lv
- Department of Gastroenterology and Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
| | - Hui-Guo Ding
- Department of Gastroenterology and Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
| | - Jun-Fu Zheng
- Department of Gastroenterology and Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
| | - Chun-Lei Fan
- Department of Gastroenterology and Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
| | - Lei Li
- Department of Gastroenterology and Hepatology, Beijing You An Hospital, Capital Medical University, Beijing 100069, China
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19
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Ito T, Nakamura K, Kageyama S, Korayem IM, Hirao H, Kadono K, Aziz J, Younan S, DiNorcia J, Agopian VG, Yersiz H, Farmer DG, Busuttil RW, Kupiec-Weglinski JW, Kaldas FM. Impact of Rifaximin Therapy on Ischemia/Reperfusion Injury in Liver Transplantation: A Propensity Score-Matched Analysis. Liver Transpl 2019; 25:1778-1789. [PMID: 31509643 PMCID: PMC6887108 DOI: 10.1002/lt.25633] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 08/13/2019] [Indexed: 12/22/2022]
Abstract
Intestinal microbiota is thought to play an important role in hepatic ischemia/reperfusion injury (IRI) after liver transplantation (LT). Rifaximin, a nonabsorbable antibiotic used to treat encephalopathy, exhibits antibacterial activity within the gut. We report the first study examining the impact of pre-LT rifaximin use on reducing hepatic IRI and inflammatory cell infiltration after LT. This retrospective single-center study included adult LT recipients from January 2013 through June 2016. Patients were divided into 2 groups based on duration of rifaximin use before LT: rifaximin group (≥28 days) and control group (none or <28 days). Patients receiving other antibiotics within 28 days of LT and re-LTs were excluded. Outcomes and messenger RNA (mRNA) expression in the graft were compared by 1:1 propensity score-matching and multivariate analyses. On 1:1 matching (n = 39/group), rifaximin patients had lower postoperative serum transaminase levels and lower early allograft dysfunction (EAD; 10.3% versus 33.3%; P = 0.014). Of the matched patients, 8 patients (n = 4/group) had postreperfusion liver biopsies (approximately 2 hours after reperfusion) available for mRNA analysis. Hepatic expression of CD86 (macrophage marker) and cathepsin G (neutrophil marker) was significantly lower in rifaximin patients than controls (P < 0.05). The multivariate analysis included 458 patients. Rifaximin treatment <28 days was identified as an independent risk factor EAD in all patients and those with high Model for End-Stage Liver Disease (MELD) score (MELD ≥35; n = 230). In conclusion, the propensity score-matched and multivariate analyses suggest a therapeutic role of rifaximin in reducing EAD. Pre-LT rifaximin administration exerted a protective function against early liver injury, potentially by suppressing inflammatory cell activation in the graft.
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Affiliation(s)
- Takahiro Ito
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Kojiro Nakamura
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA,Department of Surgery, Kyoto University, Kyoto,
Japan
| | - Shoichi Kageyama
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Islam M. Korayem
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA,Hepato-Pancreato-Biliary Surgery Unit, Department of
Surgery, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Hirofumi Hirao
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Kentaro Kadono
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Justine Aziz
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Stephanie Younan
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Joseph DiNorcia
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Vatche G. Agopian
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Hasan Yersiz
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Douglas G. Farmer
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Ronald W. Busuttil
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Jerzy W. Kupiec-Weglinski
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
| | - Fady M. Kaldas
- The Dumont-UCLA Transplantation Center, Division of Liver
and Pancreas Transplantation, Department of Surgery, David Geffen School of
Medicine, University of California, Los Angeles, CA
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20
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Shamseya MM, Madkour MA. Rifaximin: A reasonable alternative for norfloxacin in the prevention of spontaneous bacterial peritonitis in patients with HCV-related liver cirrhosis. ALEXANDRIA JOURNAL OF MEDICINE 2019. [DOI: 10.1016/j.ajme.2015.09.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Mohammed M. Shamseya
- Department of Clinical and Experimental Internal Medicine, Medical Research Institute, University of Alexandria, EgyptDepartment of Clinical and Experimental Internal Medicine, Medical Research Institute, University of Alexandria, Egypt
| | - Marwa A. Madkour
- Department of Clinical and Experimental Internal Medicine, Medical Research Institute, University of Alexandria, EgyptDepartment of Clinical and Experimental Internal Medicine, Medical Research Institute, University of Alexandria, Egypt
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21
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Kawaguchi T, Suzuki F, Imamura M, Murashima N, Yanase M, Mine T, Fujisawa M, Sato I, Yoshiji H, Okita K, Suzuki K. Rifaximin-altered gut microbiota components associated with liver/neuropsychological functions in patients with hepatic encephalopathy: An exploratory data analysis of phase II/III clinical trials. Hepatol Res 2019; 49:404-418. [PMID: 30589492 PMCID: PMC6849579 DOI: 10.1111/hepr.13300] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Revised: 12/14/2018] [Accepted: 12/17/2018] [Indexed: 12/15/2022]
Abstract
AIMS Rifaximin (RFX), a non-systemic antibiotic, improves liver/neuropsychological functions in patients with hepatic encephalopathy (HE). We aimed to investigate the clinical profiles associated with gut bacterial loads using exploratory data analysis and the effects of RFX on the gut microbiota of patients with HE. METHODS We analyzed the data from 17 patients with HE who underwent fecal microbiota examination in phase II/III trials in Japan. Profiles associated with genera Streptococcus, Veillonella, and Lactobacillus loads were analyzed using classification and regression trees (CART). Changes in gut microbial consortia of seven patients with HE were then assessed 2 weeks after RFX treatment by principal component analysis. RESULTS In the CART, the first and second divergence variables for each higher bacterial load were as follows: (i) in Streptococcus, the number connection test-A ≥39.55 s and presence of portal-systemic shunt; (ii) in Veillonella, serum potassium levels <4.75 mEq/L and total cholesterol level <129.5 mg/dL; and (iii) in Lactobacillus, white blood cell counts ≥3.4 × 103 /μL and aspartate aminotransferase level ≥44.5 U/L. There was no significant change in total bacterial load before and after RFX treatment; however, there was a decrease in Streptococcus, Veillonella, and Lactobacillus counts after RFX treatment. CONCLUSION We report clinical profiles associated with gut bacterial loads in patients with HE, and showed that RFX altered gut microbiota components associated with liver/neuropsychological functions. Thus, RFX could improve liver/neuropsychological functions through the regulation of the gut microbial consortia in patients with HE.
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Affiliation(s)
- Takumi Kawaguchi
- Division of Gastroenterology, Department of MedicineKurume University School of MedicineKurumeJapan
| | | | - Masatoshi Imamura
- Departments of Gastroenterology and HepatologyKohnodai HospitalIchikawaJapan
| | | | - Mikio Yanase
- GastroenterologyNational Center for Global Health and MedicineTokyoJapan
| | - Tetsuya Mine
- Department of GastroenterologyTokai University HospitalIseharaJapan
| | | | - Ikuya Sato
- Development DivisionASKA Pharmaceutical Co., LtdTokyoJapan
| | - Hitoshi Yoshiji
- Third Department of Internal MedicineNara Medical UniversityKashiharaJapan
| | | | - Kazuyuki Suzuki
- Division of Hepatology, Department of Internal MedicineIwate Medical UniversityMoriokaJapan
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22
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Cuomo R, Cargiolli M, Cassarano S, Carabotti M, Annibale B. Treatment of diverticular disease, targeting symptoms or underlying mechanisms. Curr Opin Pharmacol 2018; 43:124-131. [PMID: 30291995 DOI: 10.1016/j.coph.2018.09.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 09/12/2018] [Accepted: 09/17/2018] [Indexed: 02/08/2023]
Abstract
Diverticular disease (DD) is a highly prevalent disease in western industrialized countries that encompasses a complex set of disorders. Because of its complexity and heterogeneity, both from a pathogenic and a clinical point of view, the management of this disease represent a challenge in clinical practice. This review aims to analyze and summarize the most recent evidence on the medical strategies for DD, considering separately the different stages of the disease, from prevention of diverticula formation to treatment of acute diverticulitis and prevention of recurrences. Based on some evidence, dietary fiber is useful to prevent diverticula formation and in diverticulosis, with no pharmacological treatment in these settings. Treatment of symptomatic uncomplicated diverticular disease as well as primary prevention of acute diverticulitis is based on probiotics, fibres, mesalazine and rifaximin, individually or as combination therapy, although a standard approach has not yet been defined. On the contrary, in acute diverticulitis (AD) recent acquisitions have clarified and standardized the role of systemic antibiotics, reserving its use only to complicated forms and in selected cases of uncomplicated disease. Secondary prevention of AD is essentially based on mesalazine and rifaximin but, despite promising results, no strong evidence have been produced. To date, grey areas remain in the medical management of DD.
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Affiliation(s)
- Rosario Cuomo
- Gastroenterology Department of Clinical Medicine and Surgery, School of Medicine "Federico II", Naples, Italy.
| | - Martina Cargiolli
- Gastroenterology Department of Clinical Medicine and Surgery, School of Medicine "Federico II", Naples, Italy
| | - Sara Cassarano
- Gastroenterology Department of Clinical Medicine and Surgery, School of Medicine "Federico II", Naples, Italy
| | - Marilia Carabotti
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Hospital Sant'Andrea, University Sapienza, Rome, Italy
| | - Bruno Annibale
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Hospital Sant'Andrea, University Sapienza, Rome, Italy
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23
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Rifampin Resistance in Staphylococci after Rifaximin Intake for Surgical Prophylaxis in Elective Colorectal Surgery. Antimicrob Agents Chemother 2018; 62:AAC.01353-18. [PMID: 30249689 DOI: 10.1128/aac.01353-18] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 09/12/2018] [Indexed: 12/20/2022] Open
Abstract
The aim of our study was to determine whether rifampin resistance emerges in human skin staphylococci after oral intake of rifaximin for surgical prophylaxis. Rifampin-resistant staphylococci appeared on the skin of 32 out of 74 patients (43.2%) two weeks after prophylactic treatment with rifaximin. In all cases, the resistant strains were coagulase-negative staphylococci. The resistance completely reverted after three months. This study shows the emergence of transient resistance to rifampin after rifaximin intake.
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24
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Fodor AA, Pimentel M, Chey WD, Lembo A, Golden PL, Israel RJ, Carroll IM. Rifaximin is associated with modest, transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome. Gut Microbes 2018; 10:22-33. [PMID: 29708822 PMCID: PMC6363070 DOI: 10.1080/19490976.2018.1460013] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 02/28/2018] [Accepted: 03/28/2018] [Indexed: 02/03/2023] Open
Abstract
Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between the gut microbiota and IBS, this study examined potential effects of rifaximin on the gastrointestinal microbial community in patients with IBS-D. TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label rifaximin 550 mg 3 times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive 2 repeat courses of rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. Stool samples were collected at the beginning and end of open-label treatment, at the beginning and end of the first double-blind treatment, and at the end of the study. As a secondary analysis to the TARGET 3 trial, the composition and diversity of the gut microbiota were assessed, from a random subset of patients, using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Samples from 103 patients were included. After open-label rifaximin treatment for 2 weeks, 7 taxa (e.g. Peptostreptococcaceae, Verrucomicrobiaceae, Enterobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of rifaximin were generally short-term, as there was little evidence of significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The results suggest that rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by rifaximin are causally linked to IBS-D. ClinicalTrials.gov identifier number: NCT01543178.
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Affiliation(s)
- Anthony A. Fodor
- Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina, USA
| | - Mark Pimentel
- Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - William D. Chey
- Division of Gastroenterology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Anthony Lembo
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Pamela L. Golden
- Nonclinical and Clinical Pharmacology, Clinical and Medical Affairs, Salix Pharmaceuticals, Bridgewater, New Jersey, USA**
| | - Robert J. Israel
- Nonclinical and Clinical Pharmacology, Clinical and Medical Affairs, Salix Pharmaceuticals, Bridgewater, New Jersey, USA**
| | - Ian M. Carroll
- Department of Nutrition and Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA
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25
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Lopetuso LR, Napoli M, Rizzatti G, Gasbarrini A. The intriguing role of Rifaximin in gut barrier chronic inflammation and in the treatment of Crohn’s disease. Expert Opin Investig Drugs 2018; 27:543-551. [DOI: 10.1080/13543784.2018.1483333] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Loris R. Lopetuso
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS – Università Cattolica del Sacro Cuore, Roma, Italy
| | - Marco Napoli
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS – Università Cattolica del Sacro Cuore, Roma, Italy
| | - Gianenrico Rizzatti
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS – Università Cattolica del Sacro Cuore, Roma, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS – Università Cattolica del Sacro Cuore, Roma, Italy
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26
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Gómez-Hurtado I, Gimenez P, García I, Zapater P, Francés R, González-Navajas JM, Manichanh C, Ramos JM, Bellot P, Guarner F, Such J. Norfloxacin is more effective than Rifaximin in avoiding bacterial translocation in an animal model of cirrhosis. Liver Int 2018; 38:295-302. [PMID: 28834270 DOI: 10.1111/liv.13551] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 08/09/2017] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Norfloxacin administration is useful in preventing bacterial infections in cirrhosis but associated to the generation of resistant species. Rifaximin is known to reach high concentrations in the intestinal lumen without generating relevant resistance in the intestinal flora. Our aim was to compare the effect of Norfloxacin and Rifaximin on intestinal flora composition, bacterial translocation and survival in cirrhotic rats. METHODS Cirrhosis was induced in rats by oral administration of CCl4 . Animals were divided into three groups: only CCl4 (group I, n = 10); CCl4 + Norfloxacin (group II, n = 17) and CCl4 + Rifaximin (group III, n = 14). Gut bacterial composition, bacterial translocation and cytokine levels were measured. RESULTS Forty-one rats were finally included. The incidence of viable and non-viable bacterial translocation was significantly reduced in animals receiving Norfloxacin; Rifaximin also decreased the incidence of viable and non-viable bacterial translocation, but did not reach statistical significance. Serum TNF-α levels were significantly lower in antibiotic groups. Norfloxacin modified intestinal microbiota, depleting significantly more pathobionts than Rifaximin. CONCLUSION Norfloxacin is more effective than Rifaximin in preventing bacterial translocation in rats with cirrhosis probably because of its capacity to reduce pathobionts from intestinal microbiota.
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Affiliation(s)
- Isabel Gómez-Hurtado
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
| | - Paula Gimenez
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
| | - Irma García
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
| | - Pedro Zapater
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
- Departamento Farmacología Clínica, UMH, Alicante, Spain
| | - Rubén Francés
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
- Departamento Medicina Clínica, UMH, Alicante, Spain
| | - José M González-Navajas
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
| | - Chaysavanh Manichanh
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Departamento Gastroenterología, VHIR, Barcelona, Spain
| | - José M Ramos
- Departamento Medicina Interna, HGUA, Alicante, Spain
| | - Pablo Bellot
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Instituto Investigación Sanitaria y Biomédica Alicante (ISABIAL-FISABIO), Alicante, Spain
| | - Francisco Guarner
- CIBERehd, Instituto Salud Carlos III, Madrid, Spain
- Departamento Gastroenterología, VHIR, Barcelona, Spain
| | - José Such
- Cleveland Clinic, Digestive Disease institute, Abu Dhabi, UAE
- Lerner School of Medicine, Case Western Reserve University, Cleveland, OH, USA
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27
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Cuomo R, Barbara G, Annibale B. Rifaximin and diverticular disease: Position paper of the Italian Society of Gastroenterology (SIGE). Dig Liver Dis 2017; 49:595-603. [PMID: 28215517 DOI: 10.1016/j.dld.2017.01.164] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 01/19/2017] [Accepted: 01/23/2017] [Indexed: 02/08/2023]
Abstract
Management of diverticular disease has significantly improved in the last decade. Antibiotic treatment is used for symptom relief and prevention of complications. In Italy, the non-absorbable antibiotic rifaximin is one of the most frequently used drugs, and it is perceived as the reference drug to treat symptomatic diverticular disease. Its non-systemic absorption and high faecal concentrations have oriented rifaximin use to the gastrointestinal tract, where rifaximin exerts eubiotic effects representing an additional value to its antibiotic activity. This position paper was commissioned by the Italian Society of Gastroenterology governing board for a panel of experts (RC, GB, BA) to highlight the indications for treatment of diverticular disease. There is a lack of rationale for drug use for the primary prevention of diverticulitis in patients with diverticulosis; thus, rifaximin use should be avoided. The cyclic use of rifaximin, in association with high-fibre intake, is safe and useful for the treatment of symptomatic uncomplicated diverticular disease, even if the cost-efficacy of long-term treatment remains to be determined. The use of rifaximin in the prevention of diverticulitis recurrence is promising, but the low therapeutic advantage needs to be verified. No evidence is available on the efficacy of rifaximin treatment on acute uncomplicated diverticulitis.
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Affiliation(s)
- Rosario Cuomo
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Bruno Annibale
- Medical-Surgical Science and Translational Medicine Department, Sapienza University, Rome, Italy.
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28
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Biancone L, Annese V, Ardizzone S, Armuzzi A, Calabrese E, Caprioli F, Castiglione F, Comberlato M, Cottone M, Danese S, Daperno M, D'Incà R, Frieri G, Fries W, Gionchetti P, Kohn A, Latella G, Milla M, Orlando A, Papi C, Petruzziello C, Riegler G, Rizzello F, Saibeni S, Scribano ML, Vecchi M, Vernia P, Meucci G. Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Dig Liver Dis 2017; 49:338-358. [PMID: 28161290 DOI: 10.1016/j.dld.2017.01.141] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 12/19/2016] [Accepted: 01/07/2017] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.
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Affiliation(s)
- Livia Biancone
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy.
| | - Vito Annese
- AOU Careggi, Gastroenterology, Florence, Italy
| | - Sandro Ardizzone
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco - University of Milan, Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit, Presidio Columbus, Fondazione Policlinico Gemelli Universita' Cattolica, Rome, Italy
| | - Emma Calabrese
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation, University of Milan and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda,Ospedale Policlinico di Milano, Milan, Italy
| | | | - Michele Comberlato
- Department of Gastroenterology and Digestive Endoscopy, Central Hospital, Bolzano, Italy
| | - Mario Cottone
- Division of Internal Medicine 2, IBD Unit, Hospital "Riuniti Villa Sofia-Cervello", Palermo, Italy
| | - Silvio Danese
- Humanitas Research Hospital and Humanitas University, Rozzano (Milan), Italy
| | - Marco Daperno
- Hospital "Ordine Mauriziano di Torino", Turin, Italy
| | - Renata D'Incà
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Italy
| | - Giuseppe Frieri
- University of L'Aquila, Gastroenterology Unit, L'Aquila, Italy
| | - Walter Fries
- Department of Clinical and Experimental Medicine, Clinical Unit for Chroric Bowel Disorders, University of Messina, Messina, Italy
| | - Paolo Gionchetti
- IBD Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Anna Kohn
- San Camillo-Forlanini Hospital, IBD Unit, Rome, Italy
| | | | | | - Ambrogio Orlando
- Division of Internal Medicine 2, IBD Unit, Hospital "Riuniti Villa Sofia-Cervello", Palermo, Italy
| | - Claudio Papi
- IBD Unit, San Filippo Neri Hospital, Rome, Italy
| | - Carmelina Petruzziello
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy
| | - Gabriele Riegler
- U.O. of Gastroenterology C.S. - University della Campania "Luigi Vanvitelli", Naples, Italy
| | - Fernando Rizzello
- IBD Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Simone Saibeni
- Gastroenterology Unit, Rho Hospital, ASST Rhodense, Rho, Italy
| | | | - Maurizio Vecchi
- Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato and University of Milan, San Donato Milanese, Milan, Italy
| | - Piero Vernia
- Gastroenterology Unit, Sapienza, University of Rome, Rome, Italy
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29
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Borges da Silva R, Teixeira RI, Wardell JL, Wardell SMSV, Garden SJ. Copper(ii) catalyzed synthesis of novel helical luminescent benzo[4,5]imidazo[1,2-a][1,10]phenanthrolines via an intramolecular C–H amination reaction. Org Biomol Chem 2017; 15:812-826. [DOI: 10.1039/c6ob02508k] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Novel helical luminescent benzoimidazophenanthrolines were prepared using a Cu(ii) catalyzed C–H amination reaction.
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Affiliation(s)
- Ramon Borges da Silva
- Instituto de Química
- Universidade Federal do Rio de Janeiro
- Centro Tecnológica
- Bloco A
- Cidade Universitária
| | - Rodolfo Inêz Teixeira
- Instituto de Química
- Universidade Federal do Rio de Janeiro
- Centro Tecnológica
- Bloco A
- Cidade Universitária
| | - James L. Wardell
- Instituto de Tecnologia em Fármacos – Farmanguinhos
- Fiocruz. R. Sizenando Nabuco
- Rio de Janeiro
- Brazil
- Department of Chemistry
| | | | - Simon J. Garden
- Instituto de Química
- Universidade Federal do Rio de Janeiro
- Centro Tecnológica
- Bloco A
- Cidade Universitária
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30
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Pimentel M, Cash BD, Lembo A, Wolf RA, Israel RJ, Schoenfeld P. Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity. Dig Dis Sci 2017; 62:2455-2463. [PMID: 28589238 PMCID: PMC5561162 DOI: 10.1007/s10620-017-4598-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 04/29/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). AIM To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility. METHODS Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods. RESULTS Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin (n = 37) or placebo (n = 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase, Clostridium difficile was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008-1 µg/mL] and rifampin (MIC range 0.004-0.25 µg/mL). Following double-blind rifaximin treatment, Staphylococcus isolates remained susceptible to rifaximin at all visits (MIC50 range ≤0.06-32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested. CONCLUSIONS In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics. CLINICALTRIALS. GOV IDENTIFIER NCT01543178.
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Affiliation(s)
- M. Pimentel
- 0000 0001 2152 9905grid.50956.3fGI Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 225E, Los Angeles, CA 90048 USA
| | - B. D. Cash
- 0000 0000 9552 1255grid.267153.4Division of Gastroenterology, University of South Alabama, 6000 University Commons, 75 University Blvd, S, Mobile, AL 36688 USA
| | - A. Lembo
- 0000 0000 9011 8547grid.239395.7Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215 USA
| | - R. A. Wolf
- 400 Somerset Corporate Blvd., Bridgewater, NJ 08807 USA
| | - R. J. Israel
- 400 Somerset Corporate Blvd., Bridgewater, NJ 08807 USA
| | - P. Schoenfeld
- 0000 0004 0419 7787grid.414723.7Gastroenterology and Hepatology Division, John D. Dingell VA Medical Center, 4646 John R Street, Detroit, MI 48201 USA
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Kane JS, Ford AC. Rifaximin for the treatment of diarrhea-predominant irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2016; 10:431-42. [PMID: 26753693 DOI: 10.1586/17474124.2016.1140571] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Irritable bowel syndrome (IBS) is a chronic, functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habit. The pathophysiology is unclear, but may include altered gut motility, visceral hypersensitivity, abnormal central pain processing, chronic low-grade intestinal inflammation, or disturbances in the gut microbiome. These etiological mechanisms, alongside environmental factors such as stress and anxiety, vary between individuals and represent potential targets for treatment. Rifaximin is a poorly absorbed oral antibiotic proposed to act on the gut microenvironment, used in the treatment of travelers' diarrhea and hepatic encephalopathy. Clinical trials suggest the drug can reduce global IBS symptoms and improve bloating, abdominal pain, and stool consistency in some patients with non-constipated IBS, leading to Food and Drug Administration approval in the United States. This article considers the pharmacology of rifaximin, the evidence for its use in IBS, and the safety and tolerability of the drug.
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Affiliation(s)
- John S Kane
- a Leeds Gastroenterology Institute , St James's University Hospital , Leeds , UK
| | - Alexander C Ford
- a Leeds Gastroenterology Institute , St James's University Hospital , Leeds , UK
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The Possible Innovative Use of Bifidobacterium longum W11 in Association With Rifaximin: A New Horizon for Combined Approach? J Clin Gastroenterol 2016; 50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S153-S156. [PMID: 27741162 DOI: 10.1097/mcg.0000000000000683] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
GOALS The aim of the study was to unequivocally demonstrate the nontransmissibility of the genes mediating the resistance of the strain Bifidobacterium longum W11 (LMG P-21586) to rifaximin. BACKGROUND Most antibiotic treatments can induce unfavorable side effects such as antibiotic-associated diarrhea, which is largely attributable to the disruption of the intestinal microbiota. The parallel intake of probiotic bacteria might reduce these events, even if with generally very poor results. In this regard, the use of antibiotic-resistant beneficial bacteria could represent a worthy strategy. STUDY Rifaximin was tested in parallel with rifampicin, rifapentine, and rifabutin, all rifamycin derivates, using 5 different concentrations. Susceptibility tests were performed by the disc diffusion method of Kirby-Bauer, and inhibition zones were measured after incubation at 37°C. B. longum BL03 was used as comparison. The B. longum W11 genome was sequenced on Illumina MiSeq with a 250 PE reads module. After mapping the reads with the reference bacterial genome, the alignment data were processed using FreeBayes software. RESULTS B. longum BL03 was inhibited by all antibiotics even at the lowest concentration. In contrast, the W11 strain was inhibited by rifampicin, rifabutin, and rifaximin only at the highest concentration (512 μg/mL). The genomic analysis showed a mutation into the chromosomal DNA. No transposable elements were found, and the genetic locus was not flanked by close mobile genetic elements. CONCLUSIONS B. longum W11 could be used in combined therapy with rifaximin, thus opening new focused frontiers in the probiotic era while preserving the necessary safety of use for consumers.
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Ricci A, Coppo E, Barbieri R, Debbia EA, Marchese A. The effect of sub-inhibitory concentrations of rifaximin on urease production and on other virulence factors expressed by Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus. J Chemother 2016; 29:67-73. [DOI: 10.1080/1120009x.2016.1195069] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Annalisa Ricci
- Microbiology Section “C.A. Romanzi”, DISC, University of Genoa, Genoa, Italy
| | - Erika Coppo
- Microbiology Section “C.A. Romanzi”, DISC, University of Genoa, Genoa, Italy
| | - Ramona Barbieri
- Microbiology Section “C.A. Romanzi”, DISC, University of Genoa, Genoa, Italy
| | - Eugenio A. Debbia
- Microbiology Section “C.A. Romanzi”, DISC, University of Genoa, Genoa, Italy
| | - Anna Marchese
- Microbiology Section “C.A. Romanzi”, DISC, University of Genoa, Genoa, Italy
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Jenq RR, van den Brink MRM. Antibiotic prophylaxis in allogeneic stem cell transplantation-what is the correct choice? Bone Marrow Transplant 2016; 51:1071-2. [PMID: 27214076 DOI: 10.1038/bmt.2016.144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 03/26/2016] [Indexed: 11/09/2022]
Affiliation(s)
- R R Jenq
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.,Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - M R M van den Brink
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.,Department of Medicine, Weill Cornell Medical College, New York, NY, USA.,Department of Immunology, Sloan Kettering Institute for Cancer Research, New York, NY, USA
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Soldi S, Vasileiadis S, Uggeri F, Campanale M, Morelli L, Fogli MV, Calanni F, Grimaldi M, Gasbarrini A. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clin Exp Gastroenterol 2015; 8:309-25. [PMID: 26673000 PMCID: PMC4675645 DOI: 10.2147/ceg.s89999] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response.
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Affiliation(s)
- Sara Soldi
- AAT - Advanced Analytical Technologies Srl, Piacenza, Italy
| | - Sotirios Vasileiadis
- Centre for Environmental Risk Assessment and Remediation, University of South Australia, Mawson Lakes, Australia
| | | | - Mariachiara Campanale
- Internal Medicine and Gastroenterology Division, Catholic University of Rome, Rome, Italy
| | - Lorenzo Morelli
- Microbiology Institute, Catholic University of Piacenza, Piacenza, Italy
| | | | | | | | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Division, Catholic University of Rome, Rome, Italy
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Khokhar N, Qureshi MO, Ahmad S, Ahmad A, Khan HH, Shafqat F, Salih M. Comparison of once a day rifaximin to twice a day dosage in the prevention of recurrence of hepatic encephalopathy in patients with chronic liver disease. J Gastroenterol Hepatol 2015; 30:1420-2. [PMID: 25867912 DOI: 10.1111/jgh.12970] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2015] [Indexed: 12/09/2022]
Abstract
BACKGROUND Rifaximin has been used for prevention of recurrence of hepatic encephalopathy in twice a day dosage. The drug is expensive and lower dising may be possible. OBJECTIVE To determine the efficacy of rifaximin once a day dose in the prevention of hepatic encephalopathy (HE) in patients with liver cirrhosis as compared with twice daily dose of rifaximin. METHODS This Randomized control trial was carried out at the Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan from November 2012 to February 2014. Patients with known chronic liver disease with at least one episode of HE in the past were randomized to group A (rifaximin 550 mg OD) and group B (rifaximin 550 mg BD), after fulfilling the inclusion criteria. Each patient was followed for 6 months for any episode of HE. Patients in each group were identified for any breakthrough episode of encephalopathy during this period. Data were analyzed using SPSS version 16. Chi-squared test and t-test were applied where required to determine the significant difference between the two groups. RESULTS There were a total of 306 patients: 128 patients in Group A while 178 in group B. Majority of patients (75.81%) had hepatitis C virus with mean age of 52.30 ± 9.92, MELD score 13.58 ± 8.3, and 55.22% were in Child-Pugh B. Eighty-one patients had an episode of HE during the study period. There were 27 patients in group A and 54 patients in group B with breakthrough episode of HE (P = 0.088). CONCLUSION This study suggests that there is no significant difference in rifaximin once a day or twice daily dose in preventing HE.
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Affiliation(s)
- Nasir Khokhar
- Department of Gastroenterology, Shifa International Hospital, Islamabad, Pakistan
| | | | - Shafiq Ahmad
- Department of Gastroenterology, Shifa International Hospital, Islamabad, Pakistan
| | - Aiza Ahmad
- Department of Gastroenterology, Shifa International Hospital, Islamabad, Pakistan
| | - Hamza Hassan Khan
- Department of Gastroenterology, Shifa International Hospital, Islamabad, Pakistan
| | - Farzana Shafqat
- Department of Gastroenterology, Shifa International Hospital, Islamabad, Pakistan
| | - Muhammad Salih
- Department of Gastroenterology, Shifa International Hospital, Islamabad, Pakistan
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Efficacy of rifaximin on circulating endotoxins and cytokines in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2015; 27:840-5. [PMID: 26043290 DOI: 10.1097/meg.0000000000000348] [Citation(s) in RCA: 120] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Recent studies have suggested that endotoxin-induced cytokines play an important role in nonalcoholic fatty liver disease (NAFLD). Rifaximin is a nonabsorbable antibiotic that might act on Gram-negative bacteria, thereby inhibiting endotoxin proinflammatory cytokine production in patients with NAFLD. Our aim was to investigate the efficacy of rifaximin on NAFLD. METHODS Forty-two patients with biopsy-proven NAFLD [15 steatosis, 27 nonalcoholic steatohepatitis (NASH)] were included in this prospective, open-label, observational cohort study. BMI and serum aspartate aminotransferase, alanine aminotransferase (ALT), gamma glutamyl transferase, lipid profile, ferritin, C-reactive protein, glucose, insulin, homeostatic model assessment as well as endotoxin, serum Toll-like receptor 4 (TlR4), interleukin-1α (IL-1α), IL-6, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) levels were measured before and after a 28-day administration of rifaximin (1200 mg/daily). Results were analyzed using nonparametric Wilcoxon signed-rank tests. RESULTS A mild reduction in the mean BMI (32.3 ± 6.9 vs. 31.9 ± 6.8, P = 0.02) and a significant reduction in the endotoxin (0.9 ± 0.34 vs. 0.8 ± 0.13, P = 0.03) and IL-10 (4.08 ± 0.9 vs. 3.73 ± 0.7, P = 0.006) levels in the NASH group were noted. A significant reduction was observed in serum aspartate aminotransferase (50.4 ± 39 vs. 33 ± 14, P = 0.01), ALT (72 ± 48 vs. 45.2 ± 26.3, P = 0.0001), gamma glutamyl transferase (52 ± 33 vs. 41.2 ± 21.1, P = 0.02), LDL (137 ± 34 vs. 127 ± 27.5, P = 0.03), and ferritin (142 ± 214 vs. 89.3 ± 123, P = 0.0001) in the NASH group, but only in ALT (50.4 ± 26 vs. 35.5 ± 23.25, P = 0.01), and ferritin (73.6 ± 83 vs. 55 ± 76, P = 0.004) levels decreased significantly in the steatosis group. Treatment with rifaximin did not exert a significant effect on serum levels of TLR-4, IL-1, IL-6, IL-12, or TNF-α in either group. CONCLUSION In NAFLD and especially in NASH, short-term administration of rifaximin appears to be safe and effective.
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Laterza L, Ianiro G, Scoleri I, Landi R, Bruno G, Scaldaferri F, Gaetani E, Campanale M, Gasbarrini A. Rifaximin for the treatment of diarrhoea-predominant irritable bowel syndrome. Expert Opin Pharmacother 2015; 16:607-15. [PMID: 25641072 DOI: 10.1517/14656566.2015.1007951] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Rifaximin is a non-absorbable, semisynthetic antibiotic that acts as an inhibitor of bacterial RNA synthesis, with a broad spectrum of antibacterial activity. Due to its poor absorption, rifaximin has an increased exposure to the intestine, thus it is suitable for the treatment of many gastrointestinal (GI) diseases. In irritable bowel syndrome (IBS) pathogenesis, gut microbiota impairment may play a major role. The possibility of modulating intestinal bacteria using antibiotics, in particular, rifaximin, has been demonstrated to improve IBS symptoms in non-constipation subtypes of IBS. AREAS COVERED We reviewed the use of rifaximin in diarrhoea-predominant IBS, focusing on its pharmacokinetic characteristics, its absorption in GI disease, its lack of interaction with other drugs and its new extended release formulation. EXPERT OPINION Rifaximin, with its low systemic absorption and no clinically significant interactions with other drugs, may represent a treatment of choice for IBS, mainly due to its ability to act on IBS pathogenesis, through the modulation of gut microbiota. Further studies to analyse the effect of rifaximin treatment on the composition of faecal microbiota are warranted. In particular, they need to evaluate whether resistant bacterial strains are selected and whether they are still present in the faecal sample even a long time after therapy.
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Affiliation(s)
- Lucrezia Laterza
- Catholic University of Rome, Internal Medicine and Gastroenterology Department , Largo Gemelli 8, 000168 Rome , Italy
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Bajaj JS, Barrett AC, Bortey E, Paterson C, Forbes WP. Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis. Aliment Pharmacol Ther 2015; 41:39-45. [PMID: 25339518 PMCID: PMC4284039 DOI: 10.1111/apt.12993] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 06/09/2014] [Accepted: 09/29/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Rifaximin therapy reduced risk of hepatic encephalopathy (HE) recurrence and HE-related hospitalisations during a 6-month, randomised, placebo-controlled trial (RCT) and a 24-month open-label maintenance (OLM) study. However, the impact of crossover from placebo to rifaximin therapy is unclear. AIM To study the impact of crossing over from placebo to rifaximin treatment on breakthrough HE and hospitalisation rates using a within-subjects design. METHODS Adults with cirrhosis and history of overt HE episodes, currently in HE remission, received placebo during the RCT and crossed over to rifaximin 550 mg twice daily during the OLM study. Rate of breakthrough overt HE episodes, hospitalisations and incidence and rate of adverse events (AEs) were analysed during RCT and first 6 months of OLM. RESULTS Of 82 patients randomised to placebo in the RCT who crossed over to the OLM study, 39 experienced an HE episode during the RCT compared with 14 during the OLM study (P < 0.0001). Significantly lower rates of HE events were observed with rifaximin treatment compared with placebo treatment (P < 0.0001). Rates of HE-related hospitalisation were numerically lower during rifaximin treatment compared with placebo treatment, although not significant. Rates of most common AEs, serious AEs and infection-related AEs were similar between the two treatments. CONCLUSIONS This analysis confirms the repeatability of results from the RCT on safety and efficacy of rifaximin 550 mg twice daily in reducing the risk of hepatic encephalopathy recurrence, and suggests these findings are translatable outside of a rigorous, controlled trial setting.
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Affiliation(s)
- J S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA
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Boltin D, Perets TT, Shporn E, Aizic S, Levy S, Niv Y, Dickman R. Rifaximin for small intestinal bacterial overgrowth in patients without irritable bowel syndrome. Ann Clin Microbiol Antimicrob 2014; 13:49. [PMID: 25319626 PMCID: PMC4201689 DOI: 10.1186/s12941-014-0049-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 10/08/2014] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Rifaximin is a minimally absorbed antibiotic with high luminal activity, used to treat various gastrointestinal diseases. Although rifaximin has been proposed as first line treatment for small intestinal bacterial overgrowth (SIBO), few data are available regarding its efficacy in non-IBS subjects. We aimed to assess the ability of rifaximin to normalize lactulose-H2 breath tests in non-IBS subjects with symptoms suggestive of SIBO. MATERIALS AND METHODS Consecutive non-IBS patients presenting with bloating and flatulence were prospectively recruited and submitted to lactulose-H2 breath testing (LBT). Patients who had a positive result were offered rifaximin 1200 mg daily for 10 days. Breath testing was repeated two weeks after treatment completion in all patients in order to assess for response. RESULTS A total of 19 patients with a positive result received rifaximin and repeated the breath test (7 (36.8%) males, age 56.5 ± 17.6 years). The mean peak hydrogen excretion was 13.7 ± 2.8 and 10.3 ± 7.3 ppm at baseline and following rifaximin treatment, respectively (t = 1.98, p = 0.06). LBT normalized in 8/19 (42.1%) subjects. No patients reported symptom resolution. No adverse events were reported. DISCUSSION Strengths include the study's prospective design. Limitations include the small sample size and open label design. CONCLUSION Rifaximin was not effective in normalizing LBT in our cohort of non-IBS subjects with symptoms suggestive of SIBO.
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Affiliation(s)
- Doron Boltin
- The Neurogastroenterology Service, Department of Gastroenterology, Rabin Medical Center, Beilinson Campus and Sackler Faculty of Medicine, Tel Aviv University, 39 Jabotinski Street, Petah Tikva 49100, Israel.
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Calanni F, Renzulli C, Barbanti M, Viscomi GC. Rifaximin: beyond the traditional antibiotic activity. J Antibiot (Tokyo) 2014; 67:667-70. [PMID: 25095806 DOI: 10.1038/ja.2014.106] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 07/08/2014] [Accepted: 07/14/2014] [Indexed: 12/14/2022]
Abstract
Rifaximin is a non-systemic oral antibiotic derived from rifampin and characterized by a broad spectrum of antibacterial activity against Gram-positive and -negative, aerobic and anaerobic bacteria. Rifaximin was first approved in Italy in 1987 and afterwards in many other worldwide countries for the treatment of several gastrointestinal diseases. This review updates the pharmacology and pharmacodynamics of rifaximin highlighting the different actions, beyond its antibacterial activity, such as alteration of virulence, prevention of gut mucosal adherence and bacterial translocation. Moreover, rifaximin exerts some anti-inflammatory effects with only a minimal effect on the overall composition of the gut microbiota. All these properties make rifaximin a good candidate to treat various gastrointestinal diseases.
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Affiliation(s)
- Fiorella Calanni
- Research and Development Department, Alfa Wassermann SpA, Bologna, Italy
| | - Cecilia Renzulli
- Research and Development Department, Alfa Wassermann SpA, Bologna, Italy
| | - Miriam Barbanti
- Research and Development Department, Alfa Wassermann SpA, Bologna, Italy
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Mullen KD, Sanyal AJ, Bass NM, Poordad FF, Sheikh MY, Frederick RT, Bortey E, Forbes WP. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy. Clin Gastroenterol Hepatol 2014; 12:1390-7.e2. [PMID: 24365449 DOI: 10.1016/j.cgh.2013.12.021] [Citation(s) in RCA: 150] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Revised: 12/05/2013] [Accepted: 12/06/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use. METHODS We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, N = 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n = 140). RESULTS In the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2-1427 d), with 510.5 person-years of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72). CONCLUSIONS Long-term treatment (≥24 mo) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920.
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Affiliation(s)
- Kevin D Mullen
- Case Western Reserve University School of Medicine, Cleveland, Ohio.
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia
| | - Nathan M Bass
- Divison of Gastroenterology, University of California San Francisco, San Francisco, California
| | - Fred F Poordad
- The Texas Liver Institute/University of Texas Health Science Center, San Antonio, Texas
| | - Muhammad Y Sheikh
- University of California San Francisco Fresno Medical Education Program, Fresno, California
| | - R Todd Frederick
- Division of Hepatology, California Pacific Medical Center, San Francisco, California
| | - Enoch Bortey
- Salix Pharmaceuticals, Inc, Raleigh, North Carolina
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Laghi L, Picone G, Cruciani F, Brigidi P, Calanni F, Donders G, Capozzi F, Vitali B. Rifaximin modulates the vaginal microbiome and metabolome in women affected by bacterial vaginosis. Antimicrob Agents Chemother 2014; 58:3411-20. [PMID: 24709255 PMCID: PMC4068465 DOI: 10.1128/aac.02469-14] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2014] [Accepted: 03/28/2014] [Indexed: 12/31/2022] Open
Abstract
Bacterial vaginosis (BV) is a common vaginal disorder characterized by the decrease of lactobacilli and overgrowth of Gardnerella vaginalis and resident anaerobic vaginal bacteria. In the present work, the effects of rifaximin vaginal tablets on vaginal microbiota and metabolome of women affected by BV were investigated by combining quantitative PCR and a metabolomic approach based on (1)H nuclear magnetic resonance. To highlight the general trends of the bacterial communities and metabolomic profiles in response to the antibiotic/placebo therapy, a multivariate statistical strategy was set up based on the trajectories traced by vaginal samples in a principal component analysis space. Our data demonstrated the efficacy of rifaximin in restoring a health-like condition in terms of both bacterial communities and metabolomic features. In particular, rifaximin treatment was significantly associated with an increase in the lactobacillus/BV-related bacteria ratio, as well as with an increase in lactic acid concentration and a decrease of a pool of metabolites typically produced by BV-related bacteria (acetic acid, succinate, short-chain fatty acids, and biogenic amines). Among the tested dosages of rifaximin (100 and 25 mg for 5 days and 100 mg for 2 days), 25 mg for 5 days was found to be the most effective.
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Affiliation(s)
- Luca Laghi
- Centre of Foodomics, Department of Agro-Food Science and Technology, University of Bologna, Bologna, Italy
| | - Gianfranco Picone
- Centre of Foodomics, Department of Agro-Food Science and Technology, University of Bologna, Bologna, Italy
| | - Federica Cruciani
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Patrizia Brigidi
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | | | - Gilbert Donders
- Department of Obstetrics and Gynaecology, General Hospital Heilig Hart, Tienen, and University of Antwerp, Antwerp, Belgium
| | - Francesco Capozzi
- Centre of Foodomics, Department of Agro-Food Science and Technology, University of Bologna, Bologna, Italy
| | - Beatrice Vitali
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
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Lutz P, Parcina M, Bekeredjian-Ding I, Nischalke HD, Nattermann J, Sauerbruch T, Hoerauf A, Strassburg CP, Spengler U. Impact of rifaximin on the frequency and characteristics of spontaneous bacterial peritonitis in patients with liver cirrhosis and ascites. PLoS One 2014; 9:e93909. [PMID: 24714550 PMCID: PMC3979735 DOI: 10.1371/journal.pone.0093909] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Accepted: 03/10/2014] [Indexed: 12/11/2022] Open
Abstract
Background Rifaximin is a non-absorbable antibiotic used to prevent relapses of hepatic encephalopathy which may also be a candidate for prophylaxis of spontaneous bacterial peritonitis (SBP). Aim To detect the impact of rifaximin on the occurrence and characteristics of SBP. Methods We prospectively studied all hospitalized patients that underwent a diagnostic paracentesis in our department from March 2012 to April 2013 for SBP and recorded all clinical data including type of SBP prophylaxis, prior use of rifaximin, concomitant complications of cirrhosis, as well as laboratory results and bacteriological findings. Patients were divided into the following three groups: no antibiotic prophylaxis, prophylaxis with rifaximin or with systemically absorbed antibiotic prophylaxis. Results Our study cohort comprised 152 patients with advanced liver cirrhosis, 32 of whom developed SBP during the study period. As expected, our study groups differed regarding a history of hepatic encephalopathy and SBP before inclusion into the study. None of the 17 patients on systemic antibiotic prophylaxis developed SBP while 8/27 patients on rifaximin and 24/108 without prophylaxis had SBP (p = 0.02 and p = 0.04 versus systemic antibiotics, respectively). In general, episodes of SBP were similar for patients treated with rifaximin and those without any prophylaxis. However, Escherichia coli and enterococci were dominant in the ascites of patients without any prophylaxis, while mostly klebsiella species were recovered from the ascites samples in the rifaximin group. Conclusion Rifaximin pretreatment did not lead to a reduction of SBP occurrence in hospitalized patients with advanced liver disease. However, the bacterial species causing SBP were changed by rifaximin.
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Affiliation(s)
- Philipp Lutz
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
- German Center for Infection Research
- * E-mail:
| | - Marijo Parcina
- Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany
- German Center for Infection Research
| | - Isabelle Bekeredjian-Ding
- Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany
- German Center for Infection Research
| | - Hans Dieter Nischalke
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
- German Center for Infection Research
| | - Jacob Nattermann
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
- German Center for Infection Research
| | - Tilman Sauerbruch
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Achim Hoerauf
- Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany
- German Center for Infection Research
| | - Christian P. Strassburg
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
- German Center for Infection Research
| | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
- German Center for Infection Research
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Clinical effects of rifaximin in patientswith hepatic encephalopathy intolerant or nonresponsive to previous lactulose treatment: An open-label, pilot study. Curr Ther Res Clin Exp 2014; 65:413-22. [PMID: 24672094 DOI: 10.1016/j.curtheres.2004.10.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/19/2004] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a metabolic-neurophysiologicsyndrome that occurs in patients with advanced hepatic disease. One of the main pathogenic mechanisms is represented by circulating toxins produced by the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE is mainly based on drugs that eliminate ammonia-producing bacteria. OBJECTIVES The aim of this study was to evaluate the effects of the nonabsorbable antibiotic rifaximin in patients with HE who were intolerant or nonresponsive to treatment with an oral, nonabsorbable disaccharide (lactulose). METHODS This uncontrolled, open-label, pilot study was conducted at the University of Bologna, Bologna, Italy. Patients aged ≥ 18 years with histologically proven liver cirrhosis and HE were studied. All patients were intolerant or nonresponsive to previous treatment with lactulose. Rifaximin tablets were administered to patients at a dosage of 400 mg TID for 10 days. The portal systemic encephalopathy (PSE) index was evaluated at enrollment and at the end of the treatment period. Tolerability was assessed using hematology, biochemistry, and urinalysis and by recording adverse effects (AEs). RESULTS Twenty-six patients (18 men, 8 women; mean [SD] age, 55.8 [8.0] years) were enrolled (intolerants, n = 17; nonresponders, n = 9). All patients completed the study. Significant improvement was shown in most of the 5 components of the PSE index after rifaximin administration in both intolerants and nonresponders. At the end of the 10-day treatment period, the PSE index was significantly reduced in both intolerants and nonresponders. Rifaximin was well tolerated; no clinically relevant AEs were observed during the treatment period. CONCLUSIONS This pilot study of patients with liver cirrhosis and HE who were intolerant or nonresponsive to previous treatment with an oral, nonabsorbable disaccharide suggests that treatment with rifaximin may be considered as an adjuvant or an alternative treatment in reducing HE.
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Dash SK, Chauhan M, Varma V, Sharma R, Kansal S, Chawla R. Hyperammonemic coma in a post-partum patient with undiagnosed urea cycle defect. Indian J Crit Care Med 2013; 17:107-10. [PMID: 23983417 PMCID: PMC3752861 DOI: 10.4103/0972-5229.114816] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Urea cycle disorders (UCD) are common during neonatal period, and it is rarely reported in adults. We are reporting a patient presenting with post-partum neuropsychiatric symptoms rapidly progressing to coma. Markedly raised serum ammonia level on presentation with an initial normal magnetic resonance imaging (MRI) of brain and normal liver function tests led to the suspicion of UCD, which was confirmed on the basis of urine orotic acid and elevated serum amino acid levels. We had to resort to hemodialysis to correct the hyperammonemic coma, which was unresponsive to conventional anti-ammonia measures. She exhibited remarkable improvement with a progressive decline in serum ammonia with repeated hemodialysis and made a full recovery. Timely diagnosis and early institution of hemodialysis in the setting of a poor neurological status maybe considered a suitable treatment option.
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Affiliation(s)
- Sananta Kumar Dash
- Department of Critical Care Medicine, Indraprastha Apollo Hospital, New Delhi, India
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Rifaximin in the treatment of irritable bowel syndrome: is there a high risk for development of antimicrobial resistance? J Clin Gastroenterol 2013; 47:205-11. [PMID: 23340064 DOI: 10.1097/mcg.0b013e31827559a3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Irritable bowel syndrome (IBS), a chronic, nonfatal illness is commonly encountered in clinical practice; however, treatment options are limited and often ineffectual. Despite this, there is increasing evidence that bacterial overgrowth in the bowel (dysbiosis) may be an etiological factor in IBS. This has lead to studies in which the antibiotic agent rifaximin has been used to reduce the microbial burden in the bowel, to some extent alleviating the symptoms of IBS. Rifaximin is a member of the rifamycin class of antibiotics, which when administered orally has the distinctions of being gut specific coupled with poor systemic absorption, characteristics that are suggested to limit the development of bacterial resistance. The rifamycins are currently used to treat serious human diseases including tuberculosis, meningococcal disease, methicillin-resistant Staphylococcus aureus and Clostridium difficile infections. The use of rifamycins in the treatment of these diseases is associated with the development of antibiotic resistance over time. When considering the importance of the rifamycins in the treatment of serious human diseases, the large number of patients affected by IBS, and the lack of scientific evidence available on the development of antibiotic resistance to rifaximin over the long-term when used in the gut, it is advisable that the use of rifaximin as a therapy for IBS should be limited to single, acute, short-term treatment.
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Vlachogiannakos J, Viazis N, Vasianopoulou P, Vafiadis I, Karamanolis DG, Ladas SD. Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis. J Gastroenterol Hepatol 2013; 28:450-5. [PMID: 23216382 DOI: 10.1111/jgh.12070] [Citation(s) in RCA: 173] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/12/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Cirrhotic patients are predisposed to intestinal bacterial overgrowth with translocation of bacterial products which may deteriorate liver hemodynamics. Having shown that short-term administration of rifaximin improves liver hemodynamics in decompensated cirrhosis, we conducted this study to investigate the effect of intestinal decontamination with rifaximin on the long-term prognosis of patients with alcohol-related decompensated cirrhosis (Child-Pugh > 7) and ascites. METHODS Patients who had received rifaximin and showed improved liver hemodynamics were enrolled in the current study and continued to receive rifaximin (1200 mg/day). Each patient was matched by age, sex, and Child-Pugh grade to two controls and followed up for up to 5 years, death or liver transplantation. Survival and risk of developing portal hypertension-related complications were compared between rifaximin group and controls. RESULTS Twenty three patients fulfilled the inclusion criteria and matched with 46 controls. Patients who received rifaximin had a significant lower risk of developing variceal bleeding (35% vs. 59.5%, P = 0.011), hepatic encephalopathy (31.5% vs. 47%, P = 0.034), spontaneous bacterial peritonitis (4.5% vs. 46%, P = 0.027), and hepatorenal syndrome (4.5% vs. 51%, P = 0.037) than controls. Five-year cumulative probability of survival was significantly higher in patients receiving rifaximin than in controls (61% vs. 13.5%, P = 0.012). In the multivariate analysis, rifaximin administration was independently associated with lower risk of developing variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, and higher survival. CONCLUSIONS In patients with alcohol-related decompensated cirrhosis, long-term rifaximin administration is associated with reduced risk of developing complications of portal hypertension and improved survival.
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Affiliation(s)
- Jiannis Vlachogiannakos
- Hepatogastroenterology Unit, 1st Department of Medicine-Propaedeutic, Medical School, Athens University, Laiko General Hospital, Athens, Greece.
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Lanas A, Ponce J, Bignamini A, Mearin F. One year intermittent rifaximin plus fibre supplementation vs. fibre supplementation alone to prevent diverticulitis recurrence: a proof-of-concept study. Dig Liver Dis 2013; 45:104-9. [PMID: 23092785 DOI: 10.1016/j.dld.2012.09.006] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2012] [Revised: 09/07/2012] [Accepted: 09/19/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Evidence supporting appropriate medical therapy to prevent recurrence of colonic diverticulitis is limited. Our goal was to evaluate the potential of rifaximin given periodically in addition to fibre for the prophylaxis of recurrences. METHODS We conducted a multicentre, randomized, open controlled study in patients with a recent episode of colonic diverticulitis, currently in remission. Patients received 3.5 g of high-fibre supplementation b.d. with or without one week per month of the non-absorbable antibiotic rifaximin (400 mg b.d.) for 12months. Primary endpoint was recurrence of diverticulitis, encompassing acute symptomatic flare with or without complications, analyzed by multivariable logistic regression analysis and by Cox proportional hazard method. RESULTS After randomizing 165 patients, the study was interrupted since the recruitment rate was largely below the minimum anticipated, and the trial was switched from evidence-gathering to proof-of-concept. Recurrences occurred in 10.4% of patients given rifaximin plus fibres vs. 19.3% of patients receiving fibres alone. The logistic analysis adjusted for sex, age, illness duration, time from last episode, disease localization and centre recruitment rate, yielded a significant treatment effect (odds ratio 3.20; 95% confidence interval: 1.16-8.82; P=0.025). Patients with diverticulitis diagnosed since ≥1 year receiving rifaximin also had a lower incidence of recurrences (10%; 95% confidence interval: 2-47% vs. 67%; 95% confidence interval: 37-100%). Both treatments were safe. CONCLUSIONS This study represents a proof-of concept of the efficacy of cyclic rifaximin treatment, added to fibre supplements, to reduce the risk of recurrences of diverticulitis in patients in remission.
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Affiliation(s)
- Angel Lanas
- Service of Digestive Diseases, University Hospital Lozano Blesa, IIS Aragón, CIBERehd, University of Zaragoza, Spain.
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Harputluoglu MMM, Demirel U, Gul M, Temel I, Gursoy S, Selcuk EB, Aladag M, Bilgic Y, Gunduz E, Seckin Y. Effects of rifaximin on bacterial translocation in thioacetamide-induced liver injury in rats. Inflammation 2013; 35:1512-7. [PMID: 22527146 DOI: 10.1007/s10753-012-9465-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Intestinal bacterial overgrowth (IBO) and increased mucosal permeability are suggested to increase bacterial translocation (BT) in liver injury. Rifaximin (RIF) is a minimally absorbed oral antimicrobial agent that restores gut microflora imbalance. The aim of the present study was to investigate the effects of RIF on BT frequency in thioacetamide (TAA)-induced liver injury. Group 1 was the control. In group 2 (TAA), rats received TAA daily for 3 days. In group 3 (TAA + RIF), RIF was commenced on the same day as the first dose of TAA. In group 4 (RIF), rats received only RIF. Ileal aspirate Escherichia coli counts were significantly lower in the TAA + RIF group than in TAA group. There was no difference in BT frequency between the TAA and TAA + RIF groups. Our results suggest that factors such as intestinal barrier dysfunction and impaired host immune shield, apart from IBO, play an important role in BT in this model.
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