Author Interviews, C. difficile, Hospital Acquired, JAMA / 05.05.2015

Dale N. Gerding, MD Research Physician, Edward Hines, Jr., VA Hospital Professor, Department of Medicine of Loyola University Chicago Stritch School of MedicineMedicalResearch.com Interview with: Dale N. Gerding, MD Research Physician, Edward Hines, Jr., VA Hospital Professor, Department of Medicine of Loyola University Chicago Stritch School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Gerding: Naturally occurring strains of C. difficile lack the genes for production of the toxins that cause C. difficile infection (CDI) and are known as non-toxigenic C. difficile (NTCD). These strains when ingested by patients whose normal microbiota is disrupted by antibiotic treatment will harmlessly colonize the colon and remain in the gut for weeks to months. Specific strains of NTCD found in patients were shown to colonize the gut and prevent C. difficile infection when challenged with toxigenic C. difficile strains in animal models. One such NTCD strain, NTCD-M3, was shown to be safe and well tolerated in human volunteer trials and was used in the present study to determine if it would prevent recurrence of C. difficile infection in patients who had just completed treatment with vancomycin or metronidazole of either their first CDI episode or first recurrence of C. difficile infection. 168 patients were randomized to receive by mouth in a liquid form, either 10,000 spores/day of NTCD-M3 for 7 days, 10 million spores/day for 7 days, 10 million spores/day for 14 days, or an identical placebo for 14 days.  Primary outcome was safety, and secondary outcomes were the percent who colonized the gut with NTCD-M3 in the time period from end of treatment to week 6, and the rate of recurrent CDI in the patients at week 6. The results showed that NTCD-M3 was safe and well tolerated, and colonized the gut of 69% of patients who received it. The C. difficile infection recurrence rate was 30% in the placebo patients and 11% in patients who received any of the NTCD-M3 doses (P<.006). The best dose tested was 10 million spores/day for 7 days which resulted in a recurrence rate of only 5% (p<.01 vs placebo). Colonization of the gut was not permanent, but lasted a maximum of 22 weeks. The summary conclusion is that NTCD-M3 is safe, colonized the gut, and when it colonized the gut, reduced recurrence of C. difficile infection to 2% (p<.001 vs patients who were not colonized). (more…)
Author Interviews, C. difficile, Gastrointestinal Disease, Microbiome / 01.04.2015

Michael J Sadowsky Ph.D Director, BioTechnology Institute University of MinnesotaMedicalResearch.com Interview with: Michael J Sadowsky Ph.D Director, BioTechnology Institute University of Minnesota MedicalResearch: What is the background for this study? What are the main findings? Dr. Sadowsky: Fecal microbiota transplantation (FMT) has become increasingly common in the treatment of patients with refractory Clostridium difficile infection (CDI). It also holds promise for the treatment of medical conditions ranging from inflammatory bowel and Crohn’s disease to diabetes and metabolic syndrome. In contrast to standard antibiotic therapies, which further disrupt intestinal microflora and may contribute to the recurrence of CDI, FMT restores intestinal microbiome and healthy gut function. Despite therapeutic successes, little is known about the stability of transplanted microbiota over time. This report contributes to our understanding of the short-and long-term composition of gut microbiota following Fecal microbiota transplantation. In this study, fecal samples collected before and after treatment were compared with data from the Human Microbiome Project (HMP). Treatment using FMT resulted in the rapid normalization of microbial composition in the patient, with the post-treatment profiles closely resembling the normal distribution of fecal microbiota from the donor. While the composition of fecal microbiota in the donor and recipient varied over time, both remained in the large band characterized as normal in hundreds of healthy individuals collected as part of the HMP. Furthermore, while the composition of the microflora in Fecal microbiota transplantation recipients and donors diverges over time, the recipient profiles stay within the same dynamic range as the original implanted donor material. (more…)
Author Interviews, C. difficile, CDC, Hand Washing, Outcomes & Safety / 26.02.2015

Fernanda C. Lessa, M.D., M.P.H. Centers for Disease Control and Prevention Atlanta, GAMedicalResearch.com Interview with: Fernanda C. Lessa, M.D., M.P.H. Centers for Disease Control and Prevention Atlanta, GA MedicalResearch: What is the background for this study? What are the main findings? Dr. Lessa: The epidemiology of Clostridium difficile has gone through dramatic changes over the last decade. C. difficile has become the most common cause of healthcare-associated infections in US hospitals and it has been also increasingly reported outside of healthcare settings. As the epidemiology of this pathogen changes, it is important to understand the magnitude and scope of this infection in the United States to help guide priorities for prevention. Main findings: 1)      C. difficile was responsible for almost half million infections and associated with 29,000 deaths in 2011 in the United States 2)      Among the patients who developed C. difficile, 83,000 had recurrent infections 3)      C. difficile incidence was higher among females, whites, and persons 65 years of age or older 4)       Approximately 345,400 infections occurred outside of the hospital indicating that C. difficile prevention should go beyond hospital settings. (more…)
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic / 26.11.2014

Dr. John K. DiBaise MD Gastroenterology and Hepatology Mayo Clinic, Scottsdale ArizonaMedicalResearch.com Interview with: Dr. John K. DiBaise MD Gastroenterology and Hepatology Mayo Clinic, Scottsdale Arizona Medical Research: What is the background for this study? What are the main findings? Dr. DiBaise: Despite nearly 25 years of safe and effective use of proton pump inhibitors (PPI), in recent years there have been an increasing number of reports suggesting potentially harmful effects and harmful associations with their use.  One such association with PPI use has been Clostridium difficile infection (CDI) which can cause severe and recurrent episodes of diarrhea.  Previous reports evaluating the microbes present within the gastrointestinal tract (ie, gut microbiome) of individuals with CDI have shown a reduction in overall microbial community diversity.  We studied the gut microbiome in healthy individuals both before and after using a proton pump inhibitors for one month and found a similar reduction in microbial diversity while taking the PPI that did not entirely revert back to the ‘normal’ baseline after being off the medication for a month.  While this does not demonstrate a causal association between proton pump inhibitors use and CDI, it demonstrates that PPI use creates a situation in the gut microbial environment that may increase the individual’s susceptibility to CDI. (more…)
Author Interviews, C. difficile, Gastrointestinal Disease, JAMA / 13.10.2014

Dr. Ilan Youngster, MD, MMSc Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Division of Infectious Diseases, Boston Children’s Hospital Boston, MassachusettMedicalResearch.com Interview with: Dr.  Ilan Youngster, MD, MMSc Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Division of Infectious Diseases, Boston Children’s Hospital Boston, Massachusetts Medical Research: What are the main findings of the study? Dr. Youngster: The main finding is that oral administration seems to be as safe and effective as more traditional routes of delivery like colonoscopy or nasogastric tube. This is important as it allows Fecal microbiota transplantation (FMT) to be performed without the need of invasive procedures, making it safer, cheaper and more accessible to patients. (more…)
Author Interviews, C. difficile, General Medicine, Hospital Acquired / 10.10.2014

MedicalResearch.com Interview with: Esther van Kleef London School of Hygiene and Tropical Medicine, London, UK Medical Research: What are the main findings of the study? Response:  Existing evidence reveals a wide variation in estimated excess length of hospital stay (LoS) associated with healthcare-acquired C. difficile infection (HA-CDI), ranging from 2.8 to 16.1 days. Few studies considered the time-dependent nature of healthcare-acquired C. difficile (i.e. patients that spent a longer time in hospital have an increased risk of infection), and none have considered the impact of severity of healthcare-acquired C. difficile on expected delayed discharge. Using a method that adjusted for this so-called time-dependent bias, we found that compared to non-infected patients, the excess length of stay of severe patients (defined by increased white blood cell count, serum creatinine, or temperature, or presence of colitis) was on average, twice (11.6 days; 95% CI: 3.6-19.6) that of non-severe cases (5.3 days; 95% CI: 1.1-9.5). However, severely infected patients did not have a higher daily risk of in-hospital death than non-severe patients. Overall, we estimated that healthcare-acquired C. difficile prolonged hospital stay with an average of ~7 days (95% CI: 3.5-10.9) and increased in-hospital daily death rate with 75% (Hazard Ratio (HR): 1.75; 95% CI: 1. 16 – 2.62). (more…)
Author Interviews, C. difficile, Hand Washing / 30.09.2014

Kelly R. Reveles, PharmD, PhD The University of Texas College of PharmacyMedicalResearch.com Interview with: Kelly R. Reveles, PharmD, PhD The University of Texas College of Pharmacy Medical Research: What are the main findings of the study? Dr. Reveles: Our study utilized data from the Centers for Disease Control and Prevention’s National Hospital Discharge Surveys. Patients were selected for this study if they were at least 18 years of age and had an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for Clostridium difficile infection (CDI) (ICD-9-CM code 008.45). We found that Clostridium difficile infection incidence increased from 4.5 CDI discharges/1,000 total discharges in 2001 to 8.2 CDI discharges/1,000 total discharges in 2010. Mortality varied over the study period with peak mortality occurring in 2003 (8.7%) and the lowest rate occurring in 2009 (5.6%). Median hospital length of stay (LOS) was 8 days and remained stable over the study period. In summary, the incidence of Clostridium difficile infection in U.S. hospitals nearly doubled from 2001 to 2010, with little evidence of recent decline. Additionally, there does not appear to be a significant decline in mortality or hospital LOS among patients with Clostridium difficile infection. (more…)
Author Interviews, C. difficile, Gastrointestinal Disease / 10.02.2014

Stephanie Angione PhD Candidate Brown University School of Engineering Center for Biomedical EngineeringMedicalResearch.com Interview with: Stephanie Angione PhD Candidate Brown University School of Engineering Center for Biomedical Engineering MedicalResearch.com: What are the main findings of the study? Answer: This study demonstrates the application of a novel nucleic acid detection platform to detect Clostridium difficile (C. difficile) in subjects presenting with acute diarrheal symptoms. This method amplifies three genes associated with C. difficile infection as well as genes associated with virulence attributed to the NAP1/027/BI strain. The novel PCR assay allows for simple and rapid detection of three C. difficile genes: tcdB, cdtB, and tcdC, which code for C. difficile toxin B, C. difficile binary toxin, and a protein suspected to regulate toxin production, which includes the NAP1/027/BI tcdC variant. Amplification of DNA from the tcdB, tcdC and cdtB genes can be carried out using a droplet sandwich platform that performs real-time polymerase chain reaction (PCR) in microliter droplets for the detection and identification of amplified fragments of DNA. Our technique of multiplex gene amplification provides a unique method that is both sensitive and specific to rapidly detect C. difficile in patient stool samples that can be adapted to point-of-care testing. (more…)
Author Interviews, C. difficile, Infections, NEJM / 26.09.2013

MedicalResearch.com Interview with: David W. Eyre, B.M., B.Ch. Nuffield Department of Clinical Medicine University of Oxford National Institute for Health Research (NIHR) Oxford Biomedical Research Centre John Radcliffe Hospital MedicalResearch.com: What are the main findings of this study? Dr. Eyre: All cases of Clostridium difficile in Oxfordshire were studied over 3 years. Isolates were characterized by whole genome sequencing and the data was linked to hospital databases allowing epidemiological relationships between patients at the level of the hospital ward, hospital specialty, and post code to be identified. For comparison, similar information was also available for all other patients with and without diarrhea.  Preliminary work on the genetic diversity of Clostridium difficile within individuals and between individuals within discrete outbreaks allowed reliable interpretation of transmission events using genomic data. This allowed a complete reconstruction of the pattern of transmission between affected cases in Oxfordshire to be made. The findings were: 1. Unexpectedly few cases (13%) appear to be acquired from direct ward based contact with other symptomatic cases (these have previously been thought to be the main source of infections, and the focus of prevention efforts). Another 6% were associated with other hospital contact and 3% had plausible community contacts. 2. In 13% of cases potential donors were identified gnomically but no contact, within hospitals or the community, were identified. This suggests that the existence of other modes of transmission of Clostridium difficile. 3. The sources of Clostridium difficile infections were highly genetically diverse, with 45% of cases having a genetically distinct origin - suggesting a diverse reservoir of disease, not previously appreciated 4. During the 3 years of the study the rate of Clostridium difficile in Oxfordshire fell.  Any improvement in infection control techniques would be expected to reduce the incidence of cases caused by within hospital transmission. Surprisingly, similar rates of fall occurred in both in secondary cases (considered to be acquired from hospital associated symptomatic cases) and for primary cases (cases not associated with transmission from symptomatic cases). (more…)
Author Interviews, C. difficile, Infections, Nutrition, Probiotics / 07.06.2013

MedicalResearch.com eInterview with: Dr. Reena Pattani MD Department of Medicine St. Michael’s Hospital 30 Bond Street, Toronto ON M5B 1W8 MedicalResearch.com: What are the main findings of the study? Dr. Pattani: We performed a meta-analysis of 16 studies that assessed the effectiveness of probiotics administered concurrently with antibiotics compared to the use of antibiotics alone. The use of probiotics among patients in these trials reduced the risk of antibiotic-associated diarrhea by almost 40% and decreased the rate of Clostridium difficile infection by 63%. On subgroup analysis, the reduction remained statistically significant for the subgroups of good quality trials, trials in which a primarily Lactobacillus-based regimen was used, and those studies which had a follow-up period of less than 4 weeks. (more…)