Tag Archives: c difficile

JAMA: Prevalence of Detection of CDI (C. difficile) Among Asymptomatic Children, A Systematic Review and Meta-analysis

 

 

 

Sarah R. Tougas, BScN, MD1Nidhi Lodha, MBBS, MSc1Ben Vandermeer, PhD2et alDiane L. Lorenzetti, PhD3Phillip I. Tarr, MD4,5Gillian A. M. Tarr, PhD6Linda Chui, PhD7Otto G. Vanderkooi, MD8,9Stephen B. Freedman, MDCM, MSc10,11

JAMA Pediatr. Published online August 2, 2021. doi:10.1001/jamapediatrics.2021.2328

 

Question  What is the prevalence of Clostridioides difficile detection among asymptomatic children across the age spectrum?

Findings  In this systemic review and meta-analysis of 95 studies with 19 186 participants, the prevalence of detection of toxigenic and nontoxigenic C difficile was greatest (41%) among infants aged 6 to 12 months and was lowest (12%) among children aged 5 to 18 years. The prevalence of toxigenic C difficile detection was greatest (14%) among infants aged 6 to 12 months.

Meaning  These findings suggest that test result interpretation should include consideration of the high likelihood of C difficile colonization in young children.

Abstract

Importance  Detection of Clostridioides difficile has frequently been described in asymptomatic infants and children, but accurate estimates across the age spectrum are unavailable.

Objective  To assess the prevalence of C difficile detection among asymptomatic children across the age spectrum.

Data Sources  This systematic review and meta-analysis included a search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, Scopus, and Web of Science for articles published from January 1, 1990, to December 31, 2020. Search terms included Clostridium difficilePeptoclostridium difficileClostridioides difficileCDF OR CDI OR c diff OR c difficileClostridium infections OR cd positive diarrhea OR cd positive diarrhea OR Clostridium difficile OR Peptoclostridium difficile OR pseudomembranous colitis OR pseudomembranous enterocolitisenterocolitis, and pseudomembranous. These were combined with the following terms: bacterial colonization and colonization OR colonized OR colonizing OR epidemiology OR prevalence OR seroprevalence.

Study Selection  Studies were screened independently by 2 authors. Studies were included if they reported testing for C difficile among asymptomatic children (ie, children without diarrhea) younger than 18 years.

Data Extraction and Synthesis  Data were extracted independently and in duplicate by 2 reviewers. Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. Data were pooled using a random-effects model.

Main Outcomes and Measures  The primary outcome was prevalence of C difficile detection among asymptomatic children. Secondary outcomes included prevalence of toxigenic vs nontoxigenic strains of C difficile and prevalence of C difficile detection stratified by geographic region, income status, testing method, and year of testing.

Results  A total of 95 studies with 19 186 participants were included. Rates of detection of toxigenic or nontoxigenic C difficile were greatest among infants aged 6 to 12 months (41%; 95% CI, 32%-50%) and decreased to 12% (95% CI, 7%-18%) among children aged 5 to 18 years. The prevalence of toxigenic C difficile colonization was lower, peaking at 14% (95% CI, 8%-21%) among infants aged 6 to 12 months and decreasing to 6% (95% CI, 2%-11%) among children older than 5 years. Although prevalence differed by geographic region (ie, North and South America vs Europe: β, −0.151, P = .001; North and South America vs Western Pacific: β, 0.136, P = .007), there was no difference by testing method (ie, culture vs polymerase chain reaction: β, 0.069, P = .052; culture vs enzyme immunoassay: β, −0.178, P = .051), income class (low-middle income vs high income: β, −0.144, P = .23; upper-middle vs high income: β, −0.020, P = .64), or period (before 1990 vs 2010-2020: β, −0.125, P = .19; 1990-1999 vs 2010-2020: β, −0.037, P = .42; 2000-2009 vs 2010-2020: β, −0.006, P = .86).

Conclusions and Relevance  In this systematic review and meta-analysis, C difficile colonization rates among children were greatest at 6 to 12 months of age and decreased thereafter. These estimates may provide context for interpreting C difficile test results among young children.

To review the article in its entirety please click on the following link to be redirected.  Thank you.

https://jamanetwork.com/journals/jamapediatrics/article-abstract/2782616

Contagion Live Presents: Where Are We With Clostridioides Difficile?

MEDIA PARTNER

In this episode, our 1 Big Question is: Looking at C diff as a whole, would you say the medical community is doing a better job overall of treatment and what challenges remain?

We interviewed Sahil Khanna, MBBS, MS, who is professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic; Glenn Tillotson, PhD, FIDSA, FCCP, GST Micro LLC; Payal K. Patel, MD, MPH, Division of Infectious Diseases

assistant professor, University of Michigan Health System and medical director of Antimicrobial Stewardship, VA Ann Arbor; and Anurag Malani, MD, infectious diseases specialist, St. Joseph Hospital, and a fellow of Infectious Diseases Society of America (IDSA).

https://www.contagionlive.com/view/where-are-we-with-clostridioides-difficile-

American Society of Colon and Rectal Surgeons (ASCRS) June 2021 Clinical Practice Guidelines: Management of a CDI

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Clostridioides difficile Infection

Poylin, Vitaliy M.D.1; Hawkins, Alexander T. M.D., M.P.H.2; Bhama, Anuradha R. M.D.3; Boutros, Marylise M.D.4; Lightner, Amy L. M.D.5; Khanna, Sahil M.B.B.S., M.S.6; Paquette, Ian M. M.D.7; Feingold, Daniel L. M.D.8; Prepared by the Clinical Practice Guidelines Committee of The American Society of Colon and Rectal Surgeons

Author Information
Diseases of the Colon & Rectum: June 2021 – Volume 64 – Issue 6 – p 650-668
doi: 10.1097/DCR.0000000000002047
 

The American Society of Colon and Rectal Surgeons (ASCRS) is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and develop clinical practice guidelines based on the best available evidence. Although not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines.

These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician considering all the circumstances presented by the individual patient.

STATEMENT OF THE PROBLEM

Clostridioides difficile, formerly known as Clostridium difficile, is an anaerobic, gram-positive, bacillus bacterium that can be a normal inhabitant of the human colon and is most commonly transmitted via a fecal-oral route.1 Alterations in the bacterial component of the microbiota, most often due to the use of antibiotics, can lead to ecological changes that select for both population growth of C difficile as well as the induction of pathogenic behavior.2,3 Although the number of patients with C difficile infection (CDI) in the United States appears relatively stable over the past decade (estimated 476,400 cases in 2011 associated with 29,000 deaths and 462,100 cases in 2017 associated with an estimated 20,500 deaths), the prevalence of the disease remains high.3–5 Although the bacterium is present in the stool of approximately 3% of healthy adults, up to 50% of those exposed to an inpatient facility may be asymptomatic carriers.5–8 Higher rates of CDI have been reported in patients after exposure to a prolonged duration of antibiotics including perioperative antibiotics and in patients with underlying comorbid conditions such as IBD or immunosuppression.9–15

Clinical manifestations of C difficile can range from an asymptomatic carrier state to mild CDI to severe, fulminant, life-threatening infection. Although descriptions of presentation and severity of disease vary in the literature, commonly used definitions are included in Table 1.16–19C difficile infection most commonly involves the colon, where it can manifest with pseudomembranes covering the colonic mucosa (“pseudomembranous colitis”). In rare circumstances, CDI may also involve the small bowel.20,21 In the early 2000s, predominantly in North America, but also in Europe, there was an increased incidence of more severe CDI due to the emergence of certain bacterial strains (ie, ribotypes) like the BI/NAP1/027/toxinotype III strain, which is associated with a life-threatening infection.22–25 Although rates of infection with this “hypervirulent” strain recently decreased in North America, rates remain significant globally.26,27

To read the article in its full entity please click on the following link to be redirected.  Thank you.

https://journals.lww.com/dcrjournal/Fulltext/2021/06000/The_American_Society_of_Colon_and_Rectal_Surgeons.5.aspx

Proton-Pump Inhibitors and Increased Risk of C. diff. Infections

 

 

 

 

 

Increased risk for Clostridium difficile (C diff) infection remained elevated for up to a year after the conclusion of treatment with proton-pump inhibitors (PPIs), according to a paper published in Clinical Infectious Diseases.

Malin Inghammar, PhD

Source and to read the article in its entirety please click on the following link to be redirected:

https://www.hcplive.com/view/elevated-risk-c-diff-proton-pump-inhibitor-use

Investigators from Copenhagen, Denmark used a nationwide cohort of adults with
a C diff infection in order to compare periods with and without exposure to PPIs. The adults were all treated between February 2010 and December 2013. The nationwide database included health information such as C diff testing, filled prescriptions, and patient characteristics. The investigators also accounted for the previous hospitalization in the previous 12 weeks in the patients, in addition to chronic disease, genetics, socioeconomic status, length of hospital stay, and antibiotic and corticosteroid use.

Ultimately, the study authors identified 3583 episodes of community-acquired C diff infection, of which 964 occurred during the current use of PPIs. This is an observation in the current literature, but what wasn’t understood was the full extent of the relationship due to missing data from randomized controlled trials, variability between studies, and insufficient adjustment for confounding.

“While a history of prior hospital admission, advanced age, and antibiotic use are well-known risk factors for C diff infection, the role of PPIs has remained controversial,” the study authors wrote.

The investigators defined new PPI use as a new prescription for individuals who had not used PPI in the prior 365 days. They split up the periods of 0-6 months and 6-12 months because in the first period, cessation was considered indeterminate use because of the possibility for intermittent use or drug exposure continuing beyond the use period. Exposure during the 6-12 month period was “unlikely.”

Of the infections that occurred with the use of PPIs, 324 occurred within 0-6 months after treatment conclusion. Additionally, 123 cases occurred between 6 and 12 months after treatment cessation.

The remainder of C diff infection cases occurred during time periods without use of PPIs, the investigators said.

Comparing the use of PPIs with nonuse, the study authors found that the adjusted estimate incidence rate ratio (IRR) was 2.03, they said. But the risk remained elevated in later time periods too: 1.54 for 0-6 months and 1.24 for 6-12 months.

“In conclusion, in this nationwide study in Denmark, we showed that exposure to PPIs was associated with a moderate increase in the risk of community-acquired C diff infection,” the study authors said while noting that the mechanism by which PPIs may increase the C diff infection risk remains unclear. “The increased risk was most prominent during current PPI use but also persisted after treatment discontinuation.”

One limitation the study authors provided for was that initial symptoms of C diff infection could have been misinterpreted and patients prescribed PPIs could not be excluded. But, they also admitted, “it is unlikely that this would lead to biased results because the symptoms of C diff infection (diarrhea) are distinct from the upper gastrointestinal symptoms that represent the most common indication for PPIs.”

MGB Biopharma Developing MGB-BP-3 a Treatment for CDI – Announces the Successful Completion of Its End-of-Phase 2 Meeting With the FDA

MGB Biopharmaa biopharmaceutical company developing MGB-BP-3, a novel antibacterial, for the treatment of Clostridioides difficile (CDI), today announces the successful completion of its End-of-Phase 2 (EOP2) meeting with the US Food and Drug Administration (FDA), an important milestone for the company and its lead product.

The EOP2 Meeting is a formal step at which companies seek confirmation that their product is considered safe to proceed to broader clinical studies and to explore any additional studies that may be required before entering into Phase 3.

At the meeting, the US FDA confirmed that the design and the endpoints of our two prospective Phase 3 studies were appropriate. The Phase 3 studies, which are expected to recruit approximately 900 patients, will include the superiority of MGB-BP-3 against vancomycin in the critical measure of sustained clinical response as one of their endpoints.

Dr Miroslav Ravic, CEO of MGB Biopharma, said, “The successful completion of the End-of-Phase 2 meeting with the FDA marks the culmination of solid scientific and clinical endeavor by the Company. The positive Phase 2 data showed that MGB-BP-3 provides high rates of Sustained Cure from CDI, a devastating disease.  We are very pleased with the guidance received from the FDA on key elements of the Phase 3 program that will support the submission of a New Drug Application (NDA).

“The global pandemic caused by COVID-19 has highlighted the importance of being adequately prepared for infectious diseases. CDI’s ongoing high mortality reminds us that this is a disease with a significant unmet medical need for which new treatments are urgently required. MGB-BP-3, with its unique mode of action, is perfectly positioned to meet the need and provide confidence to patients and clinicians that more effective treatments are just round the corner.”

Professor Thomas Louie, clinical professor at the Cumming School of Medicine at the University of AlbertaCalgary (Canada) and Principal Investigator said, “I am most pleased to have contributed to the success of the Phase 2 clinical study of MGB-BP-3. There is a real need for new agents to address CDI and it is gratifying to see this agent progressing onto its next phase of the study. CDI represents a major burden to the Canadian and US healthcare systems. A novel antibiotic that is able to kill this deadly pathogen before it is able to sporulate offers hope to patients and their families who suffer the pain and misery caused by this disease.”

MGB Biopharma is considering strategic options for the business and has engaged JMP Securities as its exclusive financial advisor.

About MGB-BP-3

MGB-BP-3 is a novel antibiotic that belongs to the Minor Groove Binder group, discovered at the University of Strathclyde, with a unique rapid bactericidal activity against Clostridioides difficile (CDI), a feature shared by no other treatment available. A recently completed Phase 2 clinical study in 33 CDI patients using three sequential ascending doses of MGB-BP-3 showed a high initial average cure of 94% in all dosages, a high average sustained cure of 95% in the 2 lower dosages, and preservation of the gut microbiota with the lower dosages. There were correspondingly low recurrence rates of less than 5% for the first two doses. MGB-BP-3 was shown to be safe and well-tolerated with no serious adverse events in either of Phase 1 or 2 clinical studies.

CDI is a serious and life-threatening infection of the large intestine and is the most frequent cause of diarrhea in hospitals and care homes. In the US alone, there are almost half a million cases every year associated with around 30,000 deaths; three people die of uncontrolled CDI each hour. CDI has been recognized as an urgent threat pathogen by the Centers for Disease Control and Prevention (CDC) in the US and is a common consequence of antibiotic treatment in hospitalized patients.

About MGB Biopharma

MGB Biopharma is a clinical-stage company developing a novel class of anti-infectives. Its lead candidate, MGB-BP-3, is an antibacterial that is active against a broad range of important multi-resistant and susceptible Gram-positive pathogens. The Company is developing an oral formulation of MGB-BP-3 for the treatment of Clostridioides difficile Infection (CDI).

In addition to its C. difficile programme, MGB Biopharma has a pipeline of early preclinical compounds against Gram-positive, Gram-negative, anti-fungal, anti-viral and anti-parasitic pathogens.

MGB Biopharma acquired rights to the proprietary minor groove binder (MGB) platform, developed at the University of StrathclydeGlasgow, with exclusive worldwide licensing rights for all anti-infective fields. This platform provides an opportunity to develop various compounds with a completely new mode of action that are distinct from the antimicrobial drugs used in clinical practice today. As a result, many MGB-based drugs could have the potential to offer significant advantages over existing anti-infectives.

The Company, founded in 2010 and headquartered in Glasgow, Scotland, is backed by Scottish investors including Archangel Investors Limited, Barwell, TRICAPITAL, Syndicate Room, and the Scottish Investment Bank, Scottish Enterprise. The company also received significant support for its clinical programme from Innovate UK.

For more information, please visit www.mgb-biopharma.com