Tag Archives: Sahil Khanna MBBS

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

Clinical Trial Study Moving Closer to Having Safe and Effective Products to Restore the Gut Microbiome for Patients with Recurrent C. difficile Infections.

Sahil Khanna, M.B.B.S.

A new study published online in the journal ClinicalInfectious Diseases looked at the use of a non-frozen capsule of microbiome restoration therapy for treating patients with recurrent C. difficile infection.

“Patients with C. difficile are typically managed with antibiotics or fecal transplantation for recurrent C. difficile,” says the study’s author, Sahil Khanna, M.B.B.S., a gastroenterologist at Mayo Clinic. Dr. Khanna says fecal transplantation has been demonstrated to have high success rates by restoring the gut microbiome of patients.  However, he says there are several challenges with fecal transplantation including standardization of the product, keeping it frozen, and mitigating the risk of infectious disease transmission during the procedure. 

To help reduce the risks, Dr. Khanna and his team studied a transplantation method using a non-frozen capsule instead of whole stool transplantation. An initial dose-finding, the investigator-initiated study looked at the efficacy of different doses of fecal matter and the safety of performing microbiome restoration therapy using an oral product, RBX7455 developed by Rebiotix, Inc. The team found no concerns related to safety.

“Our study has several implications,” says Dr. Khanna. “We think that products like capsules may be able to replace fecal transplantation that is currently done via a colonoscopy. We also think that products that are non-frozen may allow for repeat dosing and for patient-administered self-treatment at home. The good news is that we are  moving closer to having safe and effective products to restore the gut microbiome for patients with recurrent C. difficile.”

Dr. Khanna says that larger clinical trials and blinded, placebo-controlled trials are the next step in moving this potential treatment from research into practice.

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To read this article in its entirety please click on the following link to be redirected. Thank you. https://advancingthescience.mayo.edu/2020/09/29/study-moves-microbiome-based-therapies-closer-to-the-mainstream-treatment-for-c-difficile-infection/

C Diff Foundation Welcomes Dr. Sahil Khanna, M.B.B.S.

We are pleased to welcome Dr. Sahil Khanna
as a Member of the C Diff Foundation and Medical Advisory Board.

Dr. Sahil Khanna is an Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic, Rochester, MN. He is directing the Comprehensive Gastroenterology Interest group,
C. difficile Clinic, Fecal Microbiota Transplantation program and
C. difficile related Clinical Trials at Mayo Clinic, Rochester, MN.

He completed Medical School at the All India Institute of Medical Sciences, New Delhi; followed by Post Doctoral Research at University of California San Diego, CA; residency in Internal Medicine and Fellowship in Gastroenterology and Hepatology at Mayo Clinic, Rochester, MN before joining the Faculty. He also completed Masters in Clinical and Translational Sciences during his fellowship. His research and clinical interests include Epidemiology, Outcomes and Emerging Therapeutics for Clostridium difficile infection, an arena in which he has had numerous publications and presentations.

Dr. Khanna has over 100 peer-reviewed publications and serves as reviewer and on the editorial board of several journals. He has won numerous awards including the Miles and Shirley Fiterman Award, Mayo Brothers Distinguished Fellowship Award, Donald C. Balfour Mayo Clinic Alumni Association Research Award, Hartz Foundation Young Investigators’ Scholarship and the Most Distinguished Resident Physician Award from the American Association of Physicians of Indian Origin.

Learn More About Clostridium difficile (C.diff., C.difficile) infection and Recurrent CDI Clinical Trials In Progress

 

 

 

The C Diff Foundation has implemented a global campaign to raise awareness of Clostridium difficile infection (C.difficile) clinical trials, clinical studies, clinical research and observational studies evaluating interventions for C. difficile prevention, treatments, and environmental safety.

In the USA: Nearly half a million Americans suffer from Clostridium difficile (C. diff.) infections in a single year according to a study released in 2015 by the Centers for Disease Control and Prevention (CDC). Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections making C. difficile a very important cause of infectious disease death in the United States.

“Clostridium difficile infections are not only the most common cause of healthcare-acquired infections in the United States but also very common in the community in younger patients who previously were thought to be less susceptible to C. difficile. The rate of recurrent C. difficile infections is increasing tremendously and this increase is higher than the rate of primary C. difficile infections,” stated Sahil Khanna, MD, Assistant Professor of Medicine Division of Gastroenterology and Hepatology, Director of the C. difficile Clinic, Fecal Microbiota Transplantation program and C. difficile related Clinical Trials, Mayo Clinic, Rochester, MN.

Dr. Khanna also added, “It is imperative and important for clinical trials to be done to advance the development of new treatments, new medications, and new ways to prevent and treat Clostridium difficile infections.”

Individuals volunteer to participate in clinical trials in hopes of improving their own health, to access treatments that might not be available otherwise, often because they are new and not yet widely available. They help others by contributing to advances in medicine. There can also be potential risks participating in clinical trials and clinical studies. All of the known risks associated with a particular trial and or study will be discussed during the informed consent process. It will be thoroughly explained in the informed consent document that a volunteer will receive from the research staff prior to participating in any study.

To learn more about clinical research (e.g., Clostridium difficile, C.difficile) visit the U.S. Food and Drug Administration http://www.fda.gov or telephone 1-800-835-4709, The National Institutes of Health (NIH) http://www.nih.gov and ClinicalTrials.gov.

“Clinical trials are vital to improving our knowledge about how best to prevent and treat C. difficile infections. Informing patients of clinical trials is important, and in recent years several clinical trials have led to significant improvements in the treatments available for patients with C. difficile infections,” stated Mark Wilcox, MD, FRCPath, Consultant Microbiologist, Head of Microbiology and Academic Lead of Pathology Leeds Teaching Hospitals, Professor of Medical Microbiology University of Leeds Institute of Biomedical and Clinical Sciences, Lead on Clostridium difficile for Public Health England, UK.

About the U.S. Food and Drug Administration (FDA):
The FDA is responsible for protecting the public health by assuring that foods are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drug, and vaccines and other biological products and medical devices intended for human use are safe and effective. FDA’s responsibilities extend to the 50 United States, the District of Columbia, Puerto Rico, Guam, the Virgin Islands, American Samoa, and other U.S. territories and possessions.

About the National Institutes of Health (NIH):
The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency making important discoveries that improve health and save lives.

About ClinicalTrials.gov
ClinicalTrials.gov is a Web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions.

Minnesota Has Declared November “C. difficile Infection Awareness Month

 

 

 

 

http://www.clipsyndicate.com/video/play/7172019

According to research, C. Diff is the most common infection in U.S. hospitals within the last decade.

The state of Minnesota has declared November C. difficile Infection Awareness Month.” According to research, C. Diff is the most common infection in U.S. hospitals within the last decade.

Doctors at Mayo Clinic want people to know that they can get the infection even outside of hospitals. They also say once you get it, it’s easier to get it each time.

Dr. Sahil Khanna said ways to prevent C. diff is to wash hands and avoid unnecessary antibiotics.

He said Mayo Clinic is also studying whether or not there could be a vaccination for C. Diff.

“So there’s a large multi-center study that’s going on right now in people who may be at risk for C. Diff infection,” Khanna said. “So if you’ve been to the hospital, if you’ve received antibiotics, those patients can be enrolled in a vaccine study to see if this vaccine would prevent C. Diff from happening.”

Mayo Clinic is also working with Minnesota-based company Rebiotix on another form of treatment for the infection where people can simply ingest a tablet.

“Newer studies are being derived where you can actually take material from donor stool, process donor stool in a lab, and derive all the good bacteria that you need from the donor stool and put them in capsule form,” Khanna said.

Khanna said this capsule-based treatment has more advantages than a colonoscopy-based treatment that is currently being used to treat C. Diff.