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It’s a new year with an entirely new line up of guests eager to share their C. difficile research, infection prevention methods, clinical trials in progress, the updates in the C. diff. community, and much more.
In March the post-Patient and Family Symposium presentations will broadcast, in the event you weren’t able to attend the live-online event hosted on January 15th. The first annual Patient and Family Symposium was sponsored by Seres Therapeutics
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“None of us can do this alone ~ All of us can do this together.”
A recent update (Oct. 2020) of the guidelines for Clostridioides difficile infections (CDI) might allow clinicians to accurately predict viral severity in kidney disease patients.
In 2017, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) revised their C. diff infection severity classification criteria to include an absolute serum creatinine (SCr) value above the threshold of at least 1.5 mg/dL as opposed to a relative increase from baseline of at least 1.5 times the premorbid level.
A team, led by Travis J. Carlson, Department of Clinical Sciences, High Point University Fred Wilson School of Pharmacy, sought to best define kidney injuriesas a CDI disease severity marker to make it easier to assess severe outcomes linked to CDI.
In the multicenter, cohort study, the investigators assessed adult hospitalized patients with a C. diff infection for the presence of an acute kidney injury (AKI), chronic kidney disease (CKD), and CDI severity using the 2010 and 2017 IDSA/SHEACDI guidelines.
The investigators sought primary outcomes of all-cause inpatient mortality.
In the final analysis, the investigators examined 770 C. diff infection episodes from a total of 705 patients aged 65±17 years (female, 54%; CKD, 36.5%; AKI, 29.6%).
In addition, 82 episodes (10.6%) showed discordant severity classification results because of the inclusion of more patients with preexisting chronic kidney disease in the severe disease category using an absolute SCr threshold criterion.
The absolute SCr criterion better correlated with all-cause mortality (OR, 4.04; 95% CI, 1.76-9.28; P = 0.001) than the relative increase in SCr (OR, 1.34; 95% CI, 0.62-2.89; P = 0.46).
The investigators found this corresponded with an increased likelihood of the 2017 CDI severity classification criteria to predict mortality (OR, 5.33; 95% CI, 1.81-15.72; P = 0.002) compared to the 2010 criteria ( OR, 2.71; 95% CI, 1.16-6.32; P = 0.02).
“Our findings support the 2017 IDSA/SHEA CDI severity classification criteria of a single pre-treatment SCr in future CDI guideline updates,” the authors wrote.
New data shows positive trends regarding C. diff infections and hospitalization within the last 10 years.
A team, led by Alice Y. Guh, MPH, identified cases of C. diff infections in stool specimens positive for C. diff in an individual at least 1-year-old with no positive test in the previous 8 weeks in 10 US sites.
Overall, they identified 15,461 cases in 2011—10,177 healthcare-associated cases and 5284 community-associated cases. In 2017, they identified 15,512 cases—7973 healthcare-associated cases and 7539 community-associated cases.
The estimated national burden of infections was 476,400 (95% CI, 419,900-532,900) in 2011 and 462,100 cases (95% CI, 428,600-495,600) in 2017.
After accounting for NAAT use, the adjusted estimate of the total burden of C. diff infection decreased by 24% from 2011 through 2017 (95% CI, 6-36).
Clorox Healthcare Spore* Defense Cleaner Disinfectant is a ready-to-use, low odor bleach that kills C. difficile in five minutes.
Clorox Healthcare has announced the first sporicidal solution, Clorox Healthcare Spore Defense Cleaner Disinfectant, available through the Clorox® Total 360® System, an electrostatic sprayer that combines proven electrostatic technology with trusted Clorox® solutions to easily provide superior coverage in even the hardest-to-reach places.
Clorox Healthcare Spore Defense Cleaner Disinfectant is a low fragrance bleach that kills C. diff in five minutes in addition to 42 other pathogens and can be used in sensitive patient settings. In turn, this new product provides healthcare professionals a facility-wide solution by ensuring C. diff spores, among other pathogens, are killed on hard, non-porous surfaces in patient rooms, in operating rooms, and on transport equipment often missed during manual cleaning.
Disinfecting surfaces in hospitals is challenging and time-consuming work. Research suggests only 50 percent of surfaces in patient rooms and operating rooms are effectively disinfected.¹ Proper disinfection of portable and shared medical equipment is also an important component of infection prevention as this equipment frequently becomes contaminated with healthcare-associated pathogens. In addition, such equipment often has irregular and difficult-to-clean surfaces resulting in suboptimal manual cleaning and disinfection.
In fact, a study conducted by Curtis Donskey, MD, Infectious Disease Specialist, Louis Stokes Cleveland Veterans Affairs Medical Center, found medical equipment was not disinfected after use 90 percent of the time. Sampling also showed that 27.5 percent of mobile equipment had one or more pathogens on them. These results demonstrate that mobile equipment is frequently used, infrequently cleaned, and can serve as a vector for the dissemination of pathogens.²
“Through this study, it became abundantly clear that healthcare facilities needed an efficient solution to help prevent the transmission of healthcare-associated pathogens from portable medical equipment,” said Lynda Lurie, Director of Marketing, Clorox Professional Products Company. “Clorox Healthcare Spore Defense Cleaner Disinfectant through the Clorox® Total 360® System makes a challenging, but imperative task easier for end-users while also providing complete coverage. Healthcare facilities can finally rest assured knowing they covered the germ hot spots often missed through manual cleaning.”
The Clorox® Total 360® electrostatic sprayer works by charging and atomizing Clorox Healthcare Spore Defense Cleaner Disinfectant, delivering a powerful flow of charged particles that are attracted to surfaces with a force stronger than gravity. This allows the product to reach and uniformly coat hard, non-porous surfaces including hard-to-reach areas that manual cleaning can often miss.
Clorox Healthcare Spore Defense Cleaner Disinfectant has been extensively tested for efficacy, residue, and worker protection. This solution was developed to be safe to use through the Clorox® Total 360® System and ensure the combined products effectively enhance surface coverage while reducing the time it takes to treat healthcare surfaces.
PROVEN EFFICACY AGAINST HEALTHCARE FACILITIES’ TOUGHEST CHALLENGES
Dr. Donskey examined the efficiency of the sporicidal solution against C. diff reduction on healthcare surfaces in the real-world including wheelchairs, portable equipment, and waiting rooms. Findings showed the Clorox® Total 360®System with Spore Defense was just as effective as bleach wipes in reducing C. diff spores inoculated on wheelchairs but could be applied in one-fourth of the time, providing healthcare facilities with a rapid and effective means to reduce spore contamination on surfaces like never before.³
“When it comes to the cleaning and disinfection of shared and portable medical equipment such as wheelchairs and gurneys, thoroughness of cleaning is often suboptimal and application can be challenging and time-consuming, especially when surfaces are irregular,” said Donskey. “This is what makes the development of this sporicidal solution and its ability to be used with electrostatic technology a substantial innovation – it provides a solution for healthcare facilities that wasn’t previously possible.”
With broad surface compatibility, low residue profile, 43 pathogen kill claims, and low odor, Clorox Healthcare Spore Defense Cleaner Disinfectant is easily implementable for facility-wide use. Spore Defense also meets the EPA Emerging Viral Pathogen designation for use against SARS-CoV-2, the virus that causes COVID-19.
To learn more about the Donskey studies, please view the white paper/case study here. To learn more about Clorox Healthcare Spore Defense Cleaner Disinfectant and the Clorox® Total 360® System, please visit CloroxHealthcare.com.
Notes ¹ Bhalla A., Pultz N.J., Gries D.M. et al. “Acquisition of Nosocomial Pathogens on Hands After Contact With Environmental Surfaces Near Hospitalized Patients.” Infection Control Hospital Epidemiology. 2004 Feb;25(2): 164–7 ² Donskey, C., Study Update: Cleveland VAMC showcases Clorox Total 360 Spore Defense results at IDWeek 2019. Cloroxpro. Accessed April 3, 2020. ³ Donskey, C., Evaluation of a novel sporicidal spray disinfectant for decontamination of surfaces in healthcare. CloroxPro. Accessed April 3, 2020. ∗ Clostridium difficile spores only
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;382:1320-1330).
At first glance, the study, which used data from 10 sites around the United States to derive a national estimate of the incidence of C. difficile infection (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, 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, adding that it only should be used in patients who have acute diarrhea with no obvious alternative explanation and risk factors for CDI such as 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 clinical false positives and unnecessary treatment,” Khanna emphasized.
An alternative testing approach 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:e1-e48). NAAT should be reserved for instances in which results from GDH and EIA are inconclusive, the guidelines recommend.
Laboratories are increasingly adopting a two-step protocol of GDH and EIA, but “NAAT remains the most commonly used test method,” Khanna said.
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 approved for the 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,” Ly explained.
For a first recurrence of CDI, the IDSA/SHEA guidelinesrecommend 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.
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 compared with vancomycin (N Engl J Med 2011;364:422-431), 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 beta-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 (https://bit.ly/2Teockd).
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 (https://bit.ly/31q5LO0).
“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 (https://bit.ly/37sMPBX).
What would a safer and equally effective microbiota-based treatment look like?
According to Sears, although 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;517:205-208).
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,” Dr. Sears said, “whether it’s an orally or rectally administered product.”
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Our guest James Boone, M.S., discusses Inflammatory Bowel Disease patients who are highly susceptible to C. difficile infections. The two diseases have similar symptoms, but very different treatments. This episode will examine the diagnostic methods which can distinguish between inflammatory bowel disease and a C. difficile infection, discuss testing guidelines, and touch upon recent clinical research and advances.
Low glutamate dehydrogenase levels are associated with colonization in Clostridium difficile PCR-only positive patients with inflammatory bowel disease