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Revista Espanola de Quimioterapia :... Oct 2022Tuberculosis continues to be a major public health problem. A priority objective is the implementation of early diagnosis, contact investigation and latent tuberculosis... (Review)
Review
Tuberculosis continues to be a major public health problem. A priority objective is the implementation of early diagnosis, contact investigation and latent tuberculosis infection (LTBI) testing. World Health Organization (WHO) concludes that there is no gold standard for the diagnosis of LTBI; both the tuberculin test and IGRA (interferon gamma release assays) indirectly identify tuberculosis infection; both tests are considered acceptable but imperfect. WHO recommends that regimens that include rifamycins are equally effective but less toxic and more adherent than long regimens with isoniazid.
Topics: Humans; Latent Tuberculosis; Isoniazid; Interferon-gamma Release Tests; Tuberculosis; Rifamycins
PubMed: 36285867
DOI: 10.37201/req/s03.20.2022 -
Nature Reviews. Microbiology Jun 2010Antibiotic drug-target interactions, and their respective direct effects, are generally well characterized. By contrast, the bacterial responses to antibiotic drug... (Review)
Review
Antibiotic drug-target interactions, and their respective direct effects, are generally well characterized. By contrast, the bacterial responses to antibiotic drug treatments that contribute to cell death are not as well understood and have proven to be complex as they involve many genetic and biochemical pathways. In this Review, we discuss the multilayered effects of drug-target interactions, including the essential cellular processes that are inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing. We also discuss new insights into these mechanisms that have been revealed through the study of biological networks, and describe how these insights, together with related developments in synthetic biology, could be exploited to create new antibacterial therapies.
Topics: Anti-Bacterial Agents; Bacteria; Cell Wall; DNA Replication; Drug Discovery; Nucleic Acid Synthesis Inhibitors; Quinolones; RNA; Rifamycins
PubMed: 20440275
DOI: 10.1038/nrmicro2333 -
Alimentary Pharmacology & Therapeutics Mar 2017Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterised by an increased number and/or abnormal type of bacteria in the small bowel. Over... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterised by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based.
AIM
To perform a systematic review and meta-analysis to summarise evidence about the efficacy and safety of rifaximin to eradicate SIBO in adult patients.
METHODS
MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for RCTs and observational studies. Furthermore, abstract books of major European, American and Asian gastroenterological meetings were also examined.
RESULTS
Thirty-two studies involving 1331 patients were included. The overall eradication rate according to intention-to-treat analysis was 70.8% (95% CI: 61.4-78.2; I = 89.4%) and to per protocol analysis 72.9% (95% CI: 65.5-79.8; I = 87.5%). Meta-regression identified three covariates (drug dose, study design and co-therapy) independently associated with an increased eradication rate. The overall rate of adverse events was 4.6% (95% CI: 2.3-7.5; I = 63.6%). In the subset of studies (n= 10) allowing the analysis, improvement or resolution of symptoms in patients with eradicated SIBO was found to be 67.7% (95% CI: 44.7-86.9; I = 91.3%).
CONCLUSIONS
Rifaximin treatment seems to be effective and safe for the treatment of SIBO. However, the quality of the available studies is generally poor. Well-designed RCTs are needed to substantiate these findings and to establish the optimal regimen.
Topics: Adult; Bacteria; Bacterial Infections; Female; Gastroenterology; Humans; Intestine, Small; Rifamycins; Rifaximin; Syndrome
PubMed: 28078798
DOI: 10.1111/apt.13928 -
The New England Journal of Medicine Mar 2010Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established.
METHODS
In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy.
RESULTS
Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P=0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events.
CONCLUSIONS
Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.)
Topics: Aged; Anti-Infective Agents; Chronic Disease; Clostridioides difficile; Clostridium Infections; Double-Blind Method; Drug Therapy, Combination; Female; Gastrointestinal Agents; Hepatic Encephalopathy; Hospitalization; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Lactulose; Liver Cirrhosis; Male; Middle Aged; Proportional Hazards Models; Rifamycins; Rifaximin; Secondary Prevention
PubMed: 20335583
DOI: 10.1056/NEJMoa0907893 -
American Journal of Respiratory and... Apr 2023
Topics: Humans; Tuberculosis; Antitubercular Agents; Nitroimidazoles; Rifamycins
PubMed: 36630555
DOI: 10.1164/rccm.202212-2262ED -
Expert Opinion on Drug Discovery Sep 2019: The treatment of lung disease faces significant challenges due to intrinsic antibiotic resistance. New drugs are needed to cure this incurable disease. The key... (Review)
Review
: The treatment of lung disease faces significant challenges due to intrinsic antibiotic resistance. New drugs are needed to cure this incurable disease. The key anti-tubercular rifamycin, rifampicin, suffers from low potency against and is not used clinically. Recently, another member of the rifamycin class, rifabutin, was shown to be active against the opportunistic pathogen. : In this review, the authors discuss the rifamycins as a reemerging drug class for treating infections. The authors focus on the differential potency of rifampicin and rifabutin against in the context of intrinsic antibiotic resistance and bacterial uptake and metabolism. Reports of rifamycin-based drug synergies and rifamycin potentiation by host-directed therapy are evaluated. : While repurposing rifabutin for lung disease may provide some immediate relief, the repositioning (chemical optimization) of rifamycins offers long-term potential for improving clinical outcomes. Repositioning will require a multifaceted approach involving renewed screening of rifamycin libraries, medicinal chemistry to improve 'bacterial cell pharmacokinetics', better models of bacterial pathophysiology and infection, and harnessing of drug synergies and host-directed therapy towards the development of a better drug regimen.
Topics: Animals; Anti-Bacterial Agents; Drug Repositioning; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Rifabutin; Rifampin; Rifamycins
PubMed: 31195849
DOI: 10.1080/17460441.2019.1629414 -
Cold Spring Harbor Perspectives in... Jul 2016Rifamycins inhibit RNA polymerase of most bacterial genera. Rifampicin remains part of combination therapy for treating tuberculosis (TB), and for treating Gram-positive... (Review)
Review
Rifamycins inhibit RNA polymerase of most bacterial genera. Rifampicin remains part of combination therapy for treating tuberculosis (TB), and for treating Gram-positive prosthetic joint and valve infections, in which biofilms are prominent. Rifabutin has use for AIDS patients in treating mycobacterial infections TB and Mycobacterium avium complex (MAC), having fewer drug-drug interactions that interfere with AIDS medications. Rifabutin is occasionally used in combination to eradicate Helicobacter pylori (peptic ulcer disease). Rifapentine has yet to fulfill its potential in reducing time of treatment for TB. Rifaximin is a monotherapeutic agent to treat gastrointestinal (GI) disorders, such as hepatic encephalopathy, irritable bowel syndrome, and travelers' diarrhea. Rifaximin is confined to the GI tract because it is not systemically absorbed on oral dosing, achieving high local concentrations, and showing anti-inflammatory properties in addition to its antibacterial activity. Resistance issues are unavoidable with all the rifamycins when the bioburden is high, because of mutations that modify RNA polymerase.
Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Resistance, Bacterial; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Rifabutin; Rifampin; Rifamycins; Rifaximin; Tuberculosis
PubMed: 27270559
DOI: 10.1101/cshperspect.a027011 -
Risk Factors for Acquired Rifamycin and Isoniazid Resistance: A Systematic Review and Meta-Analysis.PloS One 2015Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies.
METHODS
Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies.
RESULTS
Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I2 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I2 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5th to 95th percentile 0.07 to 3.2%).
CONCLUSION
Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR. The multifactorial aetiology of ADR in a programmatic setting should be further evaluated via appropriately designed studies.
Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Resistance, Bacterial; Humans; Isoniazid; Rifamycins; Risk; Tuberculosis
PubMed: 26406228
DOI: 10.1371/journal.pone.0139017 -
Journal of Gastrointestinal and Liver... Apr 2023Various environmental factors affecting the human microbiota may lead to gut microbial imbalance and to the development of pathologies. Alterations of gut microbiota... (Review)
Review
Various environmental factors affecting the human microbiota may lead to gut microbial imbalance and to the development of pathologies. Alterations of gut microbiota have been firmly implicated in digestive diseases such as hepatic encephalopathy, irritable bowel syndrome and diverticular disease. However, while these three conditions may all be related to dysfunction of the gut-liver-brain axis, the precise pathophysiology appears to differ somewhat for each. Herein, current knowledge on the pathophysiology of hepatic encephalopathy, irritable bowel syndrome, and diverticular disease are reviewed, with a special focus on the gut microbiota modulation associated with these disorders during therapy with rifaximin. In general, the evidence for the efficacy of rifaximin in hepatic encephalopathy appears to be well consolidated, although it is less supported for irritable bowel syndrome and diverticular disease. We reviewed current clinical practice for the management of these clinical conditions and underlined the desirability of more real-world studies to fully understand the potential of rifaximin in these clinical situations and obtain even more precise indications for the use of the drug.
Topics: Humans; Rifaximin; Irritable Bowel Syndrome; Rifamycins; Hepatic Encephalopathy; Diverticular Diseases
PubMed: 37004222
DOI: 10.15403/jgld-4871 -
Expert Opinion on Drug Metabolism &... 2016Among the infectious diseases, tuberculosis (TB) remains the second most common cause of death after HIV. TB treatment requires the combination of multiple drugs... (Review)
Review
INTRODUCTION
Among the infectious diseases, tuberculosis (TB) remains the second most common cause of death after HIV. TB treatment requires the combination of multiple drugs including the rifamycin class. However, rifamycins are activators of human pregnane X receptor (PXR), a transcription factor that regulates drug metabolism, drug resistance, energy metabolism and immune response. Rifamycin-mediated PXR activation may affect the outcome of TB therapy.
AREAS COVERED
This review describes the role of PXR in modulating metabolism, efficacy, toxicity and resistance to anti-TB drugs; as well as polymorphisms of PXR that potentially affect TB susceptibility.
EXPERT OPINION
The wide range of PXR functions that mediate drug metabolism and toxicity in TB therapy are often underappreciated and thus understudied. Further studies are needed to determine the overall impact of PXR activation on the outcome of TB therapy.
Topics: Animals; Antitubercular Agents; Drug Resistance, Bacterial; Humans; Polymorphism, Genetic; Pregnane X Receptor; Receptors, Steroid; Rifamycins; Treatment Outcome; Tuberculosis
PubMed: 26592418
DOI: 10.1517/17425255.2016.1121381