Researchers Explore How to Combat Clostridium difficile

In five different studies presented at the American College of Gastroenterology (ACG)'s 75th annual scientific meeting in San Antonio, researchers explored the impact of various factors on increasing rates of Clostridium difficile infection, such as the use of proton pump inhibitors (PPIs) and the substantial increase in antibiotic use due to new National Hospital Quality Measures; strategies to combat high rates of C. difficile infections; and cuttingedge treatments for this potentially deadlyand quite commoninfection. Five studies were featured during an ACG press briefing on Oct. 18, "Attack on C. difficile: A GI Perspective: How We Can Combat this Serious Health Issue."

C. difficile associated diarrhea (CDAD) is a major cause of morbidity and increasing health care costs among hospitalized patients, as C. difficile infections have dramatically increased in recent years, with 500,000 cases in the United States annually and approximately 15,000 deaths each year, according to the U.S. Centers for Disease Control & Prevention.

Proton Pump Inhibitors Linked to Incidence of C. difficile Associated Diarrhea

While antibiotic use is the most documented risk factor for CDAD, attention has been directed towards a plausiblebut controversiallink with proton pump inhibitors (PPIs). Researchers today unveiled results of a metaanalysis of 16 observational studies, which explored the association between CDAD and PPIs. The study, "A Metaanalysis of 16 Observational Studies on ProtonPump Inhibitor Use and Risk of Clostridium difficile Associated Diarrhea" investigated the association between PPIs and CDAD from 19802010 and involved more than 1.2 million hospitalized patients.

The investigators extracted adjusted risk estimates from the studies and used a random effects metaanalysis. The summary risk estimate showed a 65 percent increase in the incidence of CDAD among PPI users, according to Sailajah Janarthanan, MD, who coauthored the study. Researchers also conducted a stratified analysis by study design and when looking at both prospective and retrospective studies, found that there was still a significant increase in C. difficile among PPI users.

The Introduction of National Hospital Quality Measures Linked to Rising C. difficile Rates

In 2004, the Joint Commission and the Centers for Medicare and Medicaid Services (CMS) introduced National Hospital Quality Measures (NHQM) to improve pneumonia and surgical infection outcomes. However, these new quality measures have resulted in a substantial increase of antibiotic usage, which researchers hypothesized has led to an increase in C. difficile associated diarrhea and colitis in an inner city hospital in New York. As a result, researchers reviewed charts of all patients with confirmed C. difficile infection admitted to the Bronx Lebanon Hospital Center from Jan. 1, 2003 to Dec. 31, 2008. Antibiotic usage for all inpatients during the same time was also reviewed.

The study, "National Quality Measures and Clostridium difficile Infection in an Inner City Hospital," found a total of 439 patients with confirmed C. difficile infection from Jan. 1, 2003 to Dec.r 31, 2008.

"We observed significant increase in Clostridium difficile infection rate between 2003 and 2006," says Ariyo Ihimoyan, MD. The number of cases per 10,000 admissions was 16 in 2003; 20 in 2004; 50 in 2005; 36 in 2006; 40 in 2007; and 58 in 2008. The total number of antibiotic doses uses per 1000 admissions was 3268 in 2003; 3536 in 2004; 4585 in 2005; 5150 in 2006; 5848 in 2007; and 5867 in 2008.

"From these findings, we conclude that the introduction of National Hospital Quality Measures have led to a substantial increase in antibiotic usage," said Dr. Ihimoyan. "We believe this resulted in an increase in Clostridium difficile infections in our patient population. Antibiotic usagerelated quality measures may have resulted in unintended complications and should be reevaluated."

How Can We Combat C. difficile?

Another study unveiled during the Oct. 18 press briefing addressed the ways hospitals, gastroenterologists and other healthcare practitioners could combat C. difficile, "Aggressive Attack on C. difficile Results in Significant Decrease in Hospital Infection Rate: the INTEGRIS Baptist Medical Center Experience."

Waging "an all out war on C. difficile," researchers implemented a number of measures over a threemonth period at INTEGRIS Baptist Medical Center, a tertiary care facility in Oklahoma City which admits approximately 26,000 patients per year and experienced an increase in C. difficile cases.

"Aimed at reducing the incidences of C. difficile infections, these measures consisted of a multifaceted attack on C. difficile, including improved prevention, early detection, review and full implementation of national infection control guidelines, and aggressive treatment measures," explains Mark H. Mellow, MD, FACG, of the Center for Digestive Health in Oklahoma City, OK. "In addition to standard isolation procedures, we also elicited suggestions from physicians and nurses to best ensure compliance, such as placing a trashcan near the door to avoid traversing the room after degowning; keeping an uncluttered sink area; using appropriate size gloves; and making stethoscopes easily accessible," says Mellow.

Mellow and his team also initiated a campaign to limit proton pump inhibitor use outside of critical care units and encouraged nursing staff to send stool for C. difficile toxin (CDT) testing if C. difficile was suspected, without waiting for physician order.

"In the 12 months prior to our interventions, the incidence of CDT positive hospitalized patients was 11.3 per 100 admissions," says Mellow. "After a 3month implementation period, the ensuing 12month positive CDT incidence fell to 6.9 per 1000 patients, a decrease in C. difficile infection incidence of 40 percent. As a result, a 'war on C. difficile' can have a significant positive impact on a hospital's rate of infection."

Cutting Edge Treatments Help Patients with C. difficile

Up to 25 percent of patients will have a recurrence of C. difficile infection, and a proportion will be refractory to antibiotics. Additional therapies for this difficulttotreat subpopulation include antibiotics, probiotics, toxinbinding medications, active vaccination, intravenous immunoglobon, and fecal bacteriotherapy (FB).

"Fecal bacteriotherapy, more commonly known as fecal transplant, has been slowly gaining ground as a rescue for recurrent and refractory cases of C. difficile associated diarrhea," says C. Brock Miller, MD, of the University of North Carolina at Chapel. Miller and his research team today reported findings from their initial experience using FB via colonoscopy, "Fecal Bacteriotherapy via Colonscopy for Refractory and Recurrent Clostridium difficile Associated Diarrhea," which showcased two patients.

The first patient, a healthy 34year old woman who developed CDAD after eight courses of antibiotics over six months, and had ongoing recurrences of CDAD, had an immediate improvement in symptoms and has been infectionfree for nine months after fresh stool donated from her healthy 40year-old sister was liquefied and delivered throughout the terminal ileum and entire colon via colonoscopy.

A second patient, a healthy 50year old female, who also developed recurrent C. difficile toxin positive diarrhea, elected to undergo FB via colonoscopy after testing and donation by her husband. She has been cured of C. difficile associated diarrhea to date, according to Miller.

"While further clinical studies and longterm followup of patients are required, fecal bacteriotherapy appears to be a viable, safe, and inexpensive option for cases of recurrent and refractory disease," says Miller.

The goal of another study unveiled today was to explore novel and inexpensive antimicrobial agents commonly found in nature in an effort to combat C. difficile in hospitals.

"For more than 2000 years in the Indian subcontinent, indigenous people have been using turmeric in their daily food," explains Rattan Patel, MD. "Traditional Indian medicine, Ayurveda, has been using this spice to help decrease the rate of gastrointestinal infection."

In the study, "Inhibiting Hospital Associated Infection of Toxigenic Clostridium difficile Using Natural Spice Turmeric (Curcumin),"  Patel and his research team found that all strains of of C. difficile were inhibited by turmeric extract (curcumin).

"Turmeric has been shown to be relatively safe in clinical studies, with more than 40 clinical trials already performed in the United States using curcumin as an intervention as per the Clinical Trail database," says Patel. "It's likely that daily use of turmeric in hospital settings, in food products like curry or soup, can potentially decrease the incidence of Clostridium difficile associated diarrhea. But more studies are needed to determine the mechanism of action of turmeric and the physiological effects of turmeric in animal models of pseudomembranous colitis," says Patel.