Category Archives: C. diff. Lab Testing

Changes In Electronic Health Records (EHR) To Guide Clinicians In C. diff. Diagnostic Stewardship – To Pause Testing When Not Clinically Indicated

An intervention that required administrative approval of all Clostridioides difficile testing after

hospital day 3 out-performed electronic health record-based support in reducing

C. difficile testing, according to a study.

“We made a series of changes in the electronic health records (EHRs) that we hoped would discourage clinicians from ordering C. difficile tests when testing was not clinically indicated, such as when patients with diarrhea had a more likely explanation such as recent laxative use, or when testing was ordered on patients who were not having diarrhea or other symptoms of C. difficile infection at all,” Lewis said. “In addition, one hospital in our system independently implemented a physician ‘gatekeeper’ to approve all C. difficile test orders for admitted patients.”

“We performed this work as part of a larger quality improvement initiative with the goal of improving the accuracy of diagnosis of C. difficile infection in order to improve quality of care for patients and decrease our health system’s publicly reported rates of C. difficile,” Sarah S. Lewis, MD, MPH, associate professor of medicine in the division of infectious diseases at Duke University Medical Center, told Healio.

“We made a series of changes in the electronic health records (EHRs) that we hoped would discourage clinicians from ordering C. difficile tests when testing was not clinically indicated, such as when patients with diarrhea had a more likely explanation such as recent laxative use, or when testing was ordered on patients who were not having diarrhea or other symptoms of
C. difficile infection at all,” Lewis said. “In addition, one hospital in our system independently implemented a physician ‘gatekeeper’ to approve all C. difficile test orders for admitted patients.”

Lewis and colleagues tested the three EHR-based interventions at three hospitals. The first intervention, initiated in January 2018, alerted clinicians ordering a test if laxatives were administered within 24 hours. The second, initiated in October 2018, canceled test orders after 24 hours. Implemented in July 2019, he third intervention involved “contextual rule-driven order questions” that required justification when laxatives were administered or there was a lack of EHR documentation of diarrhea. In February 2019, one of the three hospitals then implemented the “gatekeeper intervention” requiring approval for all C. difficile tests after 3 days in the hospital.

Sarah S. Lewis

Lewis and colleagues estimated the impact of the interventions on C. difficile testing and hospital-onset C. difficile infection (HO-CDI) using an interrupted time-series analysis. They found that C. difficile testing was already declining in the preintervention period (annual change in incidence rate [IR] = 0.79; 95% CI, 0.72-0.87) and did not decrease further with the EHR interventions.

The study demonstrated, however, that the laxative alert was temporally associated with a trend reduction in HO-CDI (annual change in IR from baseline = 0.85; 95% CI, 0.75-0.96) at two hospitals. Meanwhile, the gatekeeper intervention at the third hospital was associated with level (incidence rate ratio [IRR[ = 0.5; 95% CI, 0.42-0.6) and trend reductions in C. difficile testing (annual change in IR = 0.91; 95% CI, 0.85-0.98) and level (IRR = 0.42; 95% CI, 0.22-0.81) and trend reductions in HO-CDI (annual change in IR = 0.68; 95% CI, 0.5–0.92) relative to the baseline period, the researchers reported.

“Diagnostic stewardship, or the appropriate utilization of diagnostic tests, is important for improving quality of care. Electronic decision support in the form of alerts or background logic to reinforce the desired provider behavior is attractive because it is relatively low resource, easy to implement, and can be programmed in a way that is relatively unobtrusive to the clinical workflow,” Lewis said. “However, as we and others have seen, decision support often needs to be coupled with both provider education and some form of administrative restriction to achieve desired goals.”

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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

New Changes In Management of a C. difficile Infection (CDI)

 

 

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 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[7]: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.

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 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 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 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 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[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,” Dr. Sears said, “whether it’s an orally or rectally administered product.”

 

To review this article in its entirety, please click on the following link to be redirected:

https://www.generalsurgerynews.com/Web-Only/Article/10-20/C-difficile-Old-Disease-New-Changes-in-Management-/61037

Clostridioides difficile Infection (CDI) In Patients With Inflammatory Bowel Disease (IBD)

CDIFFRADIO.COM

 

 

 

 

 

 

 

Clostridioides difficile Infection (CDI) In Patients with Inflammatory Bowel Disease – What’s New

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.

Research Article:

Low glutamate dehydrogenase levels are associated with colonization in Clostridium difficile PCR-only positive patients with inflammatory bowel disease

Low glutamate dehydrogenase levels are associated…

Researchers Evaluate Healthcare-Onset and Healthcare-Facility-Associated C. difficile Infections

 

Authors:
Dipesh Solanky12Derek K Juang#12Scott T Johns#3Ian C Drobish12Sanjay R Mehta124Monika Kumaraswamy1245

Abstract

Objective: Lack of judicious testing can result in the incorrect diagnosis of Clostridioides difficile infection (CDI), unnecessary CDI treatment, increased costs, and falsely augmented hospital-acquired infection (HAI) rates. We evaluated facility-wide interventions used at the VA San Diego Healthcare System (VASDHS) to reduce healthcare-onset, healthcare-facility-associated CDI (HO-HCFA CDI), including the use of diagnostic stewardship with test ordering criteria.

Design: We conducted a retrospective study to assess the effectiveness of measures implemented to reduce the rate of HO-HCFA CDI at the VASDHS from fiscal year (FY)2015 to FY2018.

Interventions: Measures executed in a stepwise fashion included a hand hygiene initiative, prompt isolation of CDI patients, enhanced terminal room cleaning, reduction of fluoroquinolone and proton-pump inhibitor use, laboratory rejection of solid stool samples, and lastly diagnostic stewardship with C. difficile toxin B gene nucleic acid amplification testing (NAAT) criteria instituted in FY2018.

Results: From FY2015 to FY2018, 127 cases of HO-HCFA CDI were identified. All rate-reducing initiatives resulted in decreased HO-HCFA cases (from 44 to 13; P ≤ .05). However, the number of HO-HCFA cases (34 to 13; P ≤ .05), potential false-positive testing associated with colonization and laxative use (from 11 to 4), hospital days (from 596 to 332), CDI-related hospitalization costs (from $2,780,681 to $1,534,190) and treatment cost (from $7,158 vs $1,476) decreased substantially following the introduction of diagnostic stewardship with test criteria from FY2017 to FY2018.

Conclusions: Initiatives to decrease the risk for CDI and diagnostic stewardship of C. difficile stool NAAT significantly reduced HO-HCFA CDI rates, detection of potential false-positives associated with laxative use, and lowered healthcare costs. Diagnostic stewardship itself had the most dramatic impact on outcomes observed and served as an effective tool in reducing HO-HCFA CDI rates.

 

 

 

 

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https://pubmed.ncbi.nlm.nih.gov/32943129/

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