Latest News and Updates on C. Difficile Infection Management and Treatment

According to the Centers for Disease Control and Prevention (CDC), Clostridium difficile infection (C. difficile) “has become the most common microbial cause of healthcare-associated infections in U.S. hospitals and costs up to $4.8 billion each year in excess health care costs for acute care facilities alone.”

Statistics provided by the CDC suggest that C. difficile cause nearly 500,000 infections in patients in the US annually. In one study noted by the CDC, among infected patients, nearly 29,000 died within 30 days of being diagnosed, and more than half of those deaths (15,000) were directly attributable to C. difficile infection.

With C. difficile infection prevention being declared a national priority by the CDC, researchers, public health officials, infectious disease specialists, and others continue to research more effective ways to combat this microbe. Below, we’ve collected links and information on several recent developments.

Antibiotic Stewardship Programs Reduce Antibiotic Use and Lower Infection Rates, Just not for C. Difficile

The Center for Infectious Disease Research and Policy (CIDRAP) recently reported some good news about the effectiveness of antibiotic stewardship programs (ASPs) in reducing antibiotic usage, especially among patients in the intensive care unit.

Citing the results of a meta-analysis published in Antimicrobial Agents and Chemotherapy, the CIDRAP report noted that, following the implementation of an ASP, “hospital antimicrobial consumption across all studies declined by 19.1%, and antibiotic costs fell by 33.9%. Though a modest decrease of 12.1% in antimicrobial use occurred in general medical wards, antimicrobial use in ICUs fell by 39.5% across the four studies that looked at that parameter.”

The meta-analysis also found that ASPs were effective in curbing the use of non-antibiotic therapies. In the six studies that also monitored antifungal prescription rates, the authors reported a 39.1% decline after ASP initiation.

The use of third- and fourth generation antibiotics (such as cephalosporins, vancomycin, tigecycline, linezolid, imipenem, meropenem, and fluoroquinolones) declined by 26.6% in facilities that implemented an ASP.

The meta-analysis found that bacteria infection rates declined 4.5% in the studies that measured clinical outcomes, and length of hospital stay fell by nearly 9% in studies that measured that metric.

However, the CIDRAP report noted that ASP implementation was not “associated with declining risks for Clostridium difficile (C diff) infections.” The authors of the meta-analysis did note that, in three studies that evaluated C difficile rates, “significant publication bias favored studies that reported ASPs' negative effects.”

Is the Scope and Impact of Drug-Resistant Infection in the US Worse than Previously Thought?

Let’s just get right to the heart of this report from Reuters:

“Fifteen years after the U.S. government declared antibiotic-resistant infections to be a grave threat to public health, a Reuters investigation has found that infection-related deaths are going uncounted, hindering the nation’s ability to fight a scourge that exacts a significant human and financial toll. Even when recorded, tens of thousands of deaths from drug-resistant infections — as well as many more infections that sicken but don’t kill people – go uncounted because federal and state agencies are doing a poor job of tracking them. The Centers for Disease Control and Prevention (CDC), the go-to national public health monitor, and state health departments lack the political, legal and financial wherewithal to impose rigorous surveillance.”

The report goes on to outline how incomplete, “patchwork” infection reporting requirements for hospitals, and lax requirements in many states regarding physicians’ responsibilities when filling out death certificates, have led to deaths caused by (or at the very least associated with) MRSA and other drug-resistant pathogens to be “grossly under-reported.”

For example, according to Reuters, only 17 states require notification of C. difficile infections. Only two of the so-called “superbug” infections (MRSA bacteremia and C. difficile) are required to be reported to the CDC’s National Healthcare Safety Network surveillance program.

As they say, read the whole thing.

Tigecycline to Treat Refractory Severe Clostridium Difficile Infection

The authors of an article published in Clinical Microbiology and Infection reported on a study that compared treatment with tigecycline to standard therapy in adult patients with severe C. difficile infection (sCDI).

The retrospective cohort study compared outcomes in patients with sCDI who received tigecycline alone to outcomes in patients who received standard oral vancomycin combined with intravenous metronidazole. The primary study outcome was clinical recovery (as determined by European Society of Clinical Microbiology and Infectious Diseases guidelines); secondary outcomes were “in-hospital and 90-day all-cause mortality and relapse, colectomy and complication rates.”

A total of 90 patients with sCDI were treated (45 in each group). Patients treated with tigecycline monotherapy tended to do better in terms of cure rate, complicated disease, and CDI sepsis.

The authors reported that, compared to the group that received standard therapy, the tigecycline group had “significantly better outcomes of clinical cure (34/45, 75.6% vs. 24/45, 53.3%; p=0.02), less complicated disease course (13/45, 28.9% vs. 24/45, 53.3%; p=0.02) and less CDI sepsis (7/45, 15.6% vs. 18/45, 40.0%; p=0.009).”

Rates of mortality, disease relapse, and other measures were similar between the groups.

These results led the researchers to conclude that “tigecycline might be considered as a potential candidate for therapeutic usage in cases of sCDI refractory to standard treatment.”

C. Difficile Genome May Hold the Key to Treatment

Our good friends at Contagion Live recently reported on a study that has uncovered how the C. difficile bacteria produces toxins, which could aid the development of nonantibiotic drugs to fight C. difficile infection.

According to Contagion Live, C. difficile produces two toxins, toxin A and toxin B, that “cause life-threatening diarrhea as well as pseudomembranous colitis, toxic megacolon, perforations in the colon, sepsis and rarely death.” Researchers at the University of Texas found that strains of C. difficile with a mutation in a particular Agr locus in their genome could not produce the toxins.

“Identifying a pathway responsible for activating the production of the toxins… opens up a unique therapeutic target for the development of a novel nonantibiotic therapy for C. difficile infections,” said the study authors.

The Contagion Live article includes a quote from author Charles Darkoh, PhD, on the potential implications of these findings. “By crippling their toxin-making machinery, C. diff cannot make toxins and thus cannot cause disease. My laboratory is already working on this and was awarded a 5-year National Institutes of Health grant to investigate and develop an oral compound we have identified that inactivate the toxins and block the toxin-making machinery of C. diff by targeting this pathway,” he said.

Additional Coverage from MD Magazine:

A Novel Fecal-Based Treatment for Clostridium Difficile Infection

High Doses of Imodium Cause Serious Heart Problems, FDA Warns

Potential Future Therapy for Clostridium difficile Infections

Bile Acids Provide Novel Approach to Clostridium Difficile Treatment