Tag Archives: c diff

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

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

Research Provides New Data; C. difficile Changes In Testing and Management

 

 

 

 

 

 

Changes in Testing

For example, new data published in The New England Journal of Medicine underscore the shortcomings of advances in testing technology, suggested Sahil Khanna, MBBS, an associate professor of medicine at Mayo Clinic College of Medicine and Science, in Rochester, Minn. (2020;382[14]:1320-1330).

At first glance, the study, which used data from 10 sites nationwide to derive a national estimate of the incidence of CDI, reported a relatively unchanged rate of the disease over a six-year period: 476,400 cases in 2011 and 462,100 cases in 2017. However, Dr. Khanna noted that after adjusting for the increasing use of nucleic acid amplification testing (NAAT), the researchers concluded that the incidence of CDI had actually decreased by 24% during the study period, including a 36% drop in healthcare-acquired CDI cases.

The study highlights a problem with NAAT, according to Khanna.

“NAAT is approximately 95% sensitive in detecting the C. difficile gene, but it cannot determine if the gene is active and toxin-producing, so it has the potential for overdiagnosis and for producing clinical false positives,” he explained. “Because of this, it’s important that we interpret NAAT results in the context of patient symptoms.”

Clinicians must be selective when deciding which patients should be tested, he said, only using it in patients who have acute diarrhea with no obvious alternative explanation, and who have the risk factors for CDI. These include older age, longer hospitalization, immunosuppression, use of antibiotics, gastric acid-suppressing agents, gastrointestinal surgery, manipulation of the gastrointestinal tract, and tube feeding.

“Patients not experiencing an active infection can be colonized with C. difficile, in which case there is a risk of a clinical false positives and unnecessary treatment,” Khanna emphasized.

An alternative testing approach now recommended by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) is the use of a multistep algorithm including glutamate dehydrogenase (GDH) to identify pathogenic bacteria and enzyme immunoassay (EIA) to detect C. difficile toxin (Clin Infect Dis 2018;66[7]:e1-e48). NAAT should be reserved for instances in which results from GDH and EIA are inconclusive, the guidelines recommend.

“Unfortunately, NAAT remains the most commonly used test method,” Khanna said, adding that laboratories are increasingly adopting a two-step protocol of GDH and EIA.

Recurrent CDI mostly occurs in people:65 and older who take antibiotics and receive medical care
staying in hospitals and nursing homes for a long time with weakened immune systems

Treatment Changes

The treatment landscape for CDI also has changed over the past few years, noted Kim Ly, PharmD, a clinical pharmacy specialist in critical care and infectious diseases at Sunrise Hospital and Medical Center, in Las Vegas. Bezlotoxumab (Zinplava, Merck), a monoclonal antibody, is now approved for combination treatment of toxin B–producing CDI, along with an established antibiotic. Additionally, metronidazole, while still approved for the treatment of CDI, is no longer recommended by IDSA/SHEA as a first-line agent for primary CDI in adults.

“For severe initial episodes of CDI, oral vancomycin and fidaxomicin [Dificid, Merck] are now the preferred agents, and metronidazole is only recommended for nonsevere initial episodes when patients are unable to be treated with oral vancomycin or fidaxomicin,” Kim explained.

For a first recurrence of CDI, the IDSA/SHEA guidelines recommend administering oral vancomycin as a tapered and pulsed regimen or fidaxomicin, rather than a standard 10-day course of vancomycin. For subsequent recurrences, clinicians can use the same regimen, with the addition of a standard course of oral vancomycin followed by rifaximin or fecal microbiota transplantation (FMT).

Metronidazole comes into play again in the management of fulminant CDI, Ly noted.

“The IDSA/SHEA guidelines recommend treating this with oral or rectal vancomycin 500 mg four times daily along with intravenous metronidazole,” she explained.

Microbiota Disruption

Given that antibiotic-induced microbiota disruption “is far and away the number one precipitant for getting recurrent CDI,” selecting the CDI treatment with the least impact on the microbiota is important, said former IDSA president Cynthia Sears, MD, a professor in the Department of Medicine, Division of Infectious Diseases, at the Johns Hopkins University School of Medicine, in Baltimore.

“Vancomycin is the most commonly used therapy for CDI and its recurrences, but it decreases intestinal diversity and so impedes the recovery of the normal microbiota after CDI, setting the stage for CDI recurrence,” Sears said. “We have learned that vancomycin hits the colon with full force when taken orally because it is not absorbed, and it has off-target effects on lots of anaerobic bacteria that are essential to intestinal resistance of CDI.”

Fidaxomicin has less of an effect on the microbiota and has been shown to sometimes decrease the risk for CDI recurrence when compared with vancomycin (N Engl J Med 2011;364[5]:422-431), but it can be expensive, she said.

Fecal Microbiota Transplantation

FMT is a less expensive, highly effective treatment that has received increasingly widespread attention, specifically for the management of recurrent CDI. Despite the enthusiasm surrounding the treatment, Sears expressed significant reservations about employing it.

“While there’s no question that FMT benefits patients with recurrent CDI, I feel we don’t yet have a quality-controlled product that we know is safe as well as being effective,” she said.

Sears pointed to two recent FDA safety alerts that warned of the harm that FMT can cause. The first, from 2019, reported that stool from a single donor had not been thoroughly screened before FMT and contained extended-spectrum ss-lactamase–producing Escherichia coli. The specimen had been used in separate FMTs for two immunocompromised patients, leading to infection with the pathogen and death in one case.

In another FDA safety alert from earlier this year, the organization said a stool bank specimen that had undergone comprehensive screening nevertheless contained enteropathogenic E. coli and Shiga toxin-producing E. coli. Transfer of the stool for the treatment of recurrent CDI resulted in one nonfatal infection and one death.

“Stool banks try very hard to be sure their specimens are free of disease-causing microbes, but if you have very low-level colonization, molecular diagnostics can miss this,” Sears said. More recently, she noted, the FDA has also raised concerns about the possibility of transferring SARS-CoV-2 through FMT, given that the virus can be present in the stool of infected individuals.

What would a safer and equally effective microbiota-based treatment look like? According to Sears, while microbial diversity seems to be protective against recurrent CDI, there are suggestions that the administration of specific strains may be able to treat CDI and can be produced under the same strict quality control manufacturing processes as other FDA-approved drugs. One study published in 2015 using human and mouse samples found that colonization with Clostridium scindens, a strain of Firmicutes, increased resistance to CDI (Nature 2015;517[7533]:205-208). Many microbiota-based therapeutics are in the research pipeline as well.

“I am optimistic that we will see something emerge that’s safer and still as effective as FMT for patients, whether it’s an orally or rectally administered product,” Sears said.

 

Source:  https://www.idse.net/Bacterial-Infections/Article/12-20/C-difficile-Old-Disease-New-Changes-In-Management/62162

C Diff Foundation Members Are Here For YOU Especially During the Pandemic

To Our Dear Patients, Families, and Healthcare Professionals,

To say these times have been trying is a giant understatement. We hope that you and your families are staying safe during this period of self quarantine, social distancing and limiting your daily exposures to help flatten the curve of COVID-19.

If anything is to come of this, we hope that it will be the value of hand washing, which will in turn help to prevent the spread of Healthcare-associated infections (HAI’s).

COVID-19 is in the forefront and this pandemic has majorly changed our lives. We are living through this together while healthcare professionals, across the globe, are dedicated  in developing the best possible practices for infection prevention, treatments and safety in public health.  For up-to-date COVID-19 information, please visit the CDC website:  www.cdc.gov

Be rest assured that the C Diff Foundation members continue to work diligently to educate and advocate for C. diff.  Infection prevention,  treatments, clinical trials, diagnostics, environmental safety and support to help those diagnosed with, being treated for, and recovering from a
C. diff. Infection worldwide.

Should you find yourself needing assistance with C. diff. infection information and support, please do not hesitate to contact us. We are here for you, your families, friends and healthcare professionals to see you through, and beyond a C. diff. infection.

A huge thank you goes out from all of us here at the C Diff Foundation to the brave men and women on the front lines of this pandemic. Without you and your bravery,  we would be in a major state of disarray. Thank you for being a guiding light for us all worldwide.

Check in on your neighbors, friends and families to make sure that they are okay. Keep your spirits high and know that we will get through this together.

“None of us can do this alone ~ All of us can do this together.”

C Diff Foundation Members Are Here For YOU Even During the Pandemic

To Our Dear Patients, Families, and Healthcare Professionals,

To say these times have been trying is a giant understatement. We hope that you and your families are staying safe during this period of self quarantine, social distancing and limiting your daily exposures to help flatten the curve of COVID-19.

If anything is to come of this, we hope that it will be the value of hand washing, which will in turn help to prevent the spread of Healthcare-associated infections (HAI’s).

COVID-19 is in the forefront and this pandemic has majorly changed our lives. We are living through this together while healthcare professionals, across the globe, are dedicated  in developing the best possible practices for infection prevention, treatments and safety in public health.  For up-to-date COVID-19 information, please visit the CDC website:  www.cdc.gov

Be rest assured that the C Diff Foundation members continue to work diligently to educate and advocate for C. diff.  Infection prevention,  treatments, clinical trials, diagnostics, environmental safety and support to help those diagnosed with, being treated for, and recovering from a
C. diff. Infection worldwide.

Should you find yourself needing assistance with C. diff. infection information and support, please do not hesitate to contact us. We are here for you, your families, friends and healthcare professionals to see you through, and beyond a C. diff. infection.

A huge thank you goes out from all of us here at the C Diff Foundation to the brave men and women on the front lines of this pandemic. Without you and your bravery,  we would be in a major state of disarray. Thank you for being a guiding light for us all worldwide.

Check in on your neighbors, friends and families to make sure that they are okay. Keep your spirits high and know that we will get through this together.

“None of us can do this alone ~ All of us can do this together.”