-
European Journal of Clinical... Jul 2019Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and... (Review)
Review
Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment. In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay. The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI. Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.
Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colitis; Cross Infection; Diarrhea; Disease Reservoirs; Fecal Microbiota Transplantation; Feces; Humans; Risk Factors; Virulence
PubMed: 30945014
DOI: 10.1007/s10096-019-03539-6 -
Annals of Medicine 2020(formerly: ) infection (CDI) is a major cause of diarrhoea for inpatients as well as outpatients. Usually, CDI is healthcare-associated but the number of... (Review)
Review
(formerly: ) infection (CDI) is a major cause of diarrhoea for inpatients as well as outpatients. Usually, CDI is healthcare-associated but the number of community-acquired infections is increasing. CDI is generally associated with changes in the normal intestinal microbiota caused by administration of antibiotics. Elderly and immunocompromised patients are at greater risk for CDI and CDI recurrence. Recently, the treatment options of CDI have undergone major changes: current recommendations speak against using metronidazole for primary CDI, fidaxomicin and bezlotoxumab have been added to the treatment armamentarium and microbial replacement therapies have emerged. Several other therapies are undergoing clinical trials. In this article, we review current treatment guidelines, present the most recent data on the options to treat CDI and glance towards future developments.KEY MESSAGESThe cornerstones for the treatment of CDI are vancomycin and fidaxomicin. Metronidazole should be used only in mild-to-moderate disease in younger patients who have no or only few risk factors for recurrence.In recurrent CDI, bezlotoxumab infusion (a monoclonal antibody against toxin B) may be considered as an adjunctive therapeutic strategy in addition to the standard care provided to patients with several risk factors for recurrence.Faecal microbiota transplantation (FMT) should be offered to patients with frequently recurring CDI.
Topics: Age Factors; Anti-Bacterial Agents; Antibodies, Monoclonal; Broadly Neutralizing Antibodies; Clostridium Infections; Fecal Microbiota Transplantation; Fidaxomicin; Humans; Practice Guidelines as Topic; Recurrence; Risk Factors; Severity of Illness Index; Vancomycin
PubMed: 31801387
DOI: 10.1080/07853890.2019.1701703 -
The New England Journal of Medicine Feb 2011Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality. Patients generally have a response to oral vancomycin... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality. Patients generally have a response to oral vancomycin or metronidazole; however, the rate of recurrence is high. This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection.
METHODS
Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry. We randomly assigned patients to receive fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times daily) orally for 10 days. The primary end point was clinical cure (resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy). The secondary end points were recurrence of C. difficile infection (diarrhea and a positive result on a stool toxin test within 4 weeks after treatment) and global cure (i.e., cure with no recurrence).
RESULTS
A total of 629 patients were enrolled, of whom 548 (87.1%) could be evaluated for the per-protocol analysis. The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis (88.2% with fidaxomicin and 85.8% with vancomycin) and the per-protocol analysis (92.1% and 89.8%, respectively). Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection, in both the modified intention-to-treat analysis (15.4% vs. 25.3%, P=0.005) and the per-protocol analysis (13.3% vs. 24.0%, P=0.004). The lower rate of recurrence was seen in patients with non–North American Pulsed Field type 1 strains. The adverse-event profile was similar for the two therapies.
CONCLUSIONS
The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin. Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non–North American Pulsed Field type 1 strains. (Funded by Optimer Pharmaceuticals; ClinicalTrials.gov number, NCT00314951.)
Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Double-Blind Method; Enterocolitis, Pseudomembranous; Feces; Female; Fidaxomicin; Humans; Intention to Treat Analysis; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Secondary Prevention; Treatment Outcome; Vancomycin
PubMed: 21288078
DOI: 10.1056/NEJMoa0910812 -
Gut and Liver Jan 2019The most common cause of antibiotic-associated diarrhea is infection (CDI). Recurrent infection (rCDI) often occurs after successful treatment of CDI. Due to the... (Review)
Review
The most common cause of antibiotic-associated diarrhea is infection (CDI). Recurrent infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.
Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Enterocolitis, Pseudomembranous; Fecal Microbiota Transplantation; Humans; Recurrence; Risk Factors; Secondary Prevention
PubMed: 30400734
DOI: 10.5009/gnl18071 -
American Family Physician Feb 2020Guidelines for the diagnosis and treatment of Clostridioides difficile infection have recently been updated. Risk factors include recent exposure to health care... (Review)
Review
Guidelines for the diagnosis and treatment of Clostridioides difficile infection have recently been updated. Risk factors include recent exposure to health care facilities or antibiotics, especially clindamycin. C. difficile infection is characterized by a wide range of symptoms, from mild or moderate diarrhea to severe disease with pseudomembranous colitis, colonic ileus, toxic megacolon, sepsis, or death. C. difficile infection should be considered in patients who are not taking laxatives and have three or more episodes of unexplained, unformed stools in 24 hours. Testing in these patients should start with enzyme immunoassays for glutamate dehydrogenase and toxins A and B or nucleic acid amplification testing. In children older than 12 months, testing is recommended only for those with prolonged diarrhea and risk factors. Treatment depends on whether the episode is an initial vs. recurrent infection and on the severity of the infection based on white blood cell count, serum creatinine level, and other clinical signs and symptoms. For an initial episode of nonsevere C. difficile infection, oral vancomycin or oral fidaxomicin is recommended. Metronidazole is no longer recommended as first-line therapy for adults. Fecal microbiota transplantation is a reasonable treatment option with high cure rates in patients who have had multiple recurrent episodes and have received appropriate antibiotic therapy for at least three of the episodes. Good antibiotic stewardship is a key strategy to decrease rates of C. difficile infection. In routine or endemic settings, hands should be cleaned with either soap and water or an alcohol-based product, but during outbreaks soap and water is superior. The Infectious Diseases Society of America does not recommend the use of probiotics for prevention of C. difficile infection.
Topics: Adult; Age Factors; Aged; Anti-Bacterial Agents; Antimicrobial Stewardship; Child; Clostridioides difficile; Clostridium Infections; Fidaxomicin; Humans; Infant; Practice Guidelines as Topic; Risk Factors; Severity of Illness Index; Vancomycin
PubMed: 32003951
DOI: No ID Found -
Clinical Microbiology and Infection :... Dec 2021In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile...
SCOPE
In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as faecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults.
METHODS AND QUESTIONS
Key questions on CDI treatment were formulated by the guideline committee and included: What is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI? What is the best treatment when no oral therapy is possible? Can prognostic factors identify patients at risk for severe and recurrent CDI and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure.
RECOMMENDATIONS
Important changes compared with previous guideline include but are not limited to: metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, FMT or bezlotoxumab in addition to standard of care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.
Topics: Adult; Anti-Bacterial Agents; Antibodies, Monoclonal; Broadly Neutralizing Antibodies; Clostridioides difficile; Clostridium Infections; Fidaxomicin; Humans; Practice Guidelines as Topic; Recurrence; Societies, Medical; Vancomycin
PubMed: 34678515
DOI: 10.1016/j.cmi.2021.09.038 -
The Journal of Antimicrobial... Dec 2022Clostridioides difficile infection (CDI) remains a significant clinical challenge both in the management of severe and severe-complicated disease and the prevention of... (Review)
Review
Clostridioides difficile infection (CDI) remains a significant clinical challenge both in the management of severe and severe-complicated disease and the prevention of recurrence. Guidelines released by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America (IDSA/SHEA) and ESCMID had some consensus as well as some discrepancies in disease severity classification and treatment recommendations. We review and compare the key clinical strategies from updated IDSA/SHEA, ESCMID and current Australasian guidelines for CDI management in adults and discuss relevant issues for clinicians, particularly in the management of severe-complicated infection. Updated IDSA/SHEA and ESCMID guidelines now reflect the increased efficacy of fidaxomicin in preventing recurrence and have both promoted fidaxomicin to first-line therapy with an initial CDI episode in both non-severe and severe disease and endorsed the role of bezlotoxumab in the prevention of recurrent infection. Vancomycin remains acceptable therapy and metronidazole is not preferred. For severe-complicated infection the IDSA/SHEA recommends high-dose oral ± rectal vancomycin and IV metronidazole, whilst in an important development, ESCMID has endorsed fidaxomicin and tigecycline as part of combination anti-CDI therapy, for the first time. The role of faecal microbiota transplantation (FMT) in second CDI recurrence is now clearer, but timing and mode of FMT in severe-complicated refractory disease still requires further study.
Topics: Adult; Humans; Vancomycin; Fidaxomicin; Metronidazole; Clostridioides difficile; Clostridium Infections; Anti-Bacterial Agents
PubMed: 36441203
DOI: 10.1093/jac/dkac404 -
Gastroenterology & Hepatology Oct 2016Since the discovery of infection (CDI) in the 1970s, there has been an increase in the incidence, severity, and recurrence rate of the disease. We reviewed the recent...
Since the discovery of infection (CDI) in the 1970s, there has been an increase in the incidence, severity, and recurrence rate of the disease. We reviewed the recent CDI literature in PubMed published before February 28, 2016 that focused on advances in therapy. Despite a large number of studies describing methods for diagnosing the disease, there is currently no definitive test that identifies this infection with certainty, which complicates therapy. Recommended therapy for CDI includes oral metronidazole for mild cases and oral vancomycin or fidaxomicin for moderate to severe cases, each given for 10 to 14 days. For infection with spore-forming , this length of treatment may be insufficient to lead to cure; however, continuing antibiotics for longer periods of time may unfavorably alter the microbiome, preventing recovery. Treatment with metronidazole has been associated with an increasing failure rate, and the only clear recommended form of metronidazole for treatment of CDI is the intravenous formulation for patients unable to take oral medications. For vancomycin or fidaxomicin treatment of first CDI recurrences, the drug used in the initial bout can be repeated. For second or future recurrences, vancomycin can be given in pulsed or tapered doses. New modalities of treatment, such as bacteriotherapy and immunotherapy, show promise for the treatment of recurrent CDI.
PubMed: 27917075
DOI: No ID Found -
Clinical Infectious Diseases : An... Dec 2020Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE).
BACKGROUND
Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children.
METHODS
Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured.
RESULTS
Of 148 patients randomized, 142 were treated (30 <2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%-35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high.
CONCLUSIONS
Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI.
CLINICAL TRIALS REGISTRATION
NCT02218372.
Topics: Adolescent; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Child; Child, Preschool; Clostridioides; Clostridioides difficile; Clostridium; Clostridium Infections; Fidaxomicin; Humans; Single-Blind Method; Treatment Outcome; Vancomycin
PubMed: 31773143
DOI: 10.1093/cid/ciz1149 -
Clinical Medicine (London, England) Jun 2018Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but infection causes a spectrum of disease,... (Review)
Review
Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but infection causes a spectrum of disease, ranging from occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have provided new insights into the pathogenesis of these conditions, and have revealed a role for manipulation of the gut microbiota as a novel therapeutic approach. This review will give an overview of the assessment of these conditions, before focusing on the rapidly developing area of their treatment.
Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Diarrhea; Enterocolitis, Pseudomembranous; Fecal Microbiota Transplantation; Fidaxomicin; Humans; Metronidazole; Probiotics; Vancomycin
PubMed: 29858434
DOI: 10.7861/clinmedicine.18-3-237