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Publication: Multicenter Prevalence Study Comparing Molecular and Toxin Assays for Clostridioides difficile Surveillance, Switzerland

C. diff. RESEARCH

 

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Andreas F. Widmer, Reno Frei, Ed J. Kuijper, Mark H. Wilcox, Ruth Schindler, Violeta Spaniol, Daniel Goldenberger, Adrian Egli, Sarah Tschudin-Sutter , and Kuijper
Author affiliations: University Hospital Basel, Basel, Switzerland (A.F. Widmer, R. Frei, R. Schindler, V. Spaniol, D. Goldenberger, A. Egli, S. Tschudin-Sutter)Leiden University Medical Center, Leiden, the Netherlands (E.J. Kuijper)Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, and Leeds Teaching Hospitals, Leeds, UK (M.H. Wilcox)

Abstract

Public health authorities in the United States and Europe recommend surveillance for Clostridioides difficile infections among hospitalized patients, but differing diagnostic algorithms can hamper comparisons between institutions and countries. We compared surveillance based on the detection of C. difficile by PCR or enzyme immunoassay (EIA) in a nationwide C. difficile prevalence study in Switzerland. We included all routinely collected stool samples from hospitalized patients with diarrhea in 76 hospitals in Switzerland on 2 days, 1 in winter and 1 in summer, in 2015. EIA C. difficile detection rates were 6.4 cases/10,000 patient bed-days in winter and 5.7 cases/10,000 patient bed-days in summer. PCR detection rates were 11.4 cases/10,000 patient bed-days in winter and 7.1 cases/10,000 patient bed-days in summer. We found PCR used alone increased reported C. difficile prevalence rates by <80% compared with a 2-stage EIA-based algorithm.

 

Since its identification as a cause of antibiotic-associated pseudomembraneous colitis in 1978 (1), Clostridioides difficile has emerged as a major healthcare-associated pathogen worldwide. In the United States, C. difficile infection (CDI) rates doubled during 1996–2003 (2), and rates of CDI were reported to be 76.9 cases/10,000 discharges in 2005 (3). In a more recent national point-prevalence study including US healthcare facility in-patients, 13/1,000 patients were found to be either infected or colonized (4), a higher rate than had been previously estimated. In a national point-prevalence study of nosocomial infections in the United States, C. difficile was the most common causative pathogen overall (5). The increase largely has been attributed to the emergence of the hypervirulent strain, PCR ribotype 027 (RT027), which was identified as causative strain in 82% of cases during CDI outbreaks in Quebec, Canada, during 2001–2003 and accounted for 31% of all cases of healthcare-associated infections in the United States in 2011 (69). In Europe, CDI incidence varies across hospitals and countries with a weighted mean of 4.1 cases/10,000 patient-days per hospital in 2008 (10). The most recent study on CDI prevalence in Europe suggests an increase in the number of cases, reporting a mean of 7.0 cases/10,000 patient-bed days and ranging among countries from 0.7 to 28.7 cases/10,000 patient-bed days (11). The most common ribotype identified was RT027, which was detected in 4 countries: Germany, Hungary, Poland, and Romania (11).

To estimate and compare the burden of CDI across the United States, the US Centers for Disease Control and Prevention (CDC) began population-based CDI surveillance in 10 locations in 2011 (12). The European Centre for Disease Prevention and Control (ECDC) began coordinating CDI surveillance in acute care hospitals in Europe in 2016 (13). Both authorities provide case definitions based on different diagnostic approaches, including detection of C. difficile toxin A and B by enzyme immunoassay (EIA) or detection of toxin-producing C. difficile organisms by PCR. However, the use of different diagnostic algorithms to detect C. difficile might hamper comparisons between institutions and countries. Therefore, in a nationwide C. difficile multicenter prevalence study in Switzerland, we systematically compared surveillance measures based on detection of C. difficile in stool by either PCR as a stand-alone test or by a 2-stage algorithm consisting of an EIA to detect glutamate dehydrogenase (GDH) and toxins A and B.

Methods

Study Design

We performed a nationwide multicenter prevalence study of toxigenic C. difficile detected in stool samples routinely collected from hospitalized patients with diarrhea. Our study followed the design of a previous point-prevalence study for maximal comparability between our results and data from Europe (11). University Hospital Basel, a tertiary care center in Switzerland, coordinated the study. All hospitals participating in Swissnoso (https://www.swissnoso.chExternal Link), a national infection prevention network, were asked to participate. The Swissnoso network consists of 85 acute care hospitals that account for a total of 26,341 beds.

The Ethics Committee Northwest and Central Switzerland (Ethikkommission Nordwest-und Zentralschweiz) issued a declaration of no objection for this study. We adhered to STROBE guidelines for reporting on observational studies (14).

Sample Collection

All stool samples collected from inpatients >1 year of age with diarrhea that were submitted to the microbiology laboratory on 2 specified sampling days, 1 in winter and 1 in summer, in 2015 were eligble for inclusion. Only 1 sample per patient was included. In addition, stool samples that tested positive for toxigenic C. difficile <1 week prior to each study day also were collected from all institutions to obtain a more detailed estimate of ribotype distribution in Switzerland.

We collected the following institutional data for all hospitals and their affiliated microbiology laboratories: contact information; detailed information regarding laboratory diagnostics in place; and detailed information on the total number of admissions, number of beds, and number of patients hospitalized on the 2 days of the study. We also collected information on the total number of diagnosed CDI cases at each institution during the study year. For each eligible stool sample, we collected the following data: date of sample collection, age and gender of patient, ward location and clinical specialty, institution, whether a C. difficile test was ordered by the treating physician, and result of the C. difficile test if testing was performed at the local laboratory.

Procedures

We tested all stool samples at the Division of Clinical Microbiology of the University Hospital Basel by using a 2-stage algorithm consisting of EIA and PCR. We performed EIA to detect GDH and toxins A and B by using C. DIFF QUIK CHEK COMPLETE (Techlab, https://www.techlab.comExternal Link), following the manufacturer’s instructions. We then performed PCR to detect the toxin B gene by using the RealStar PCR Kit (Altona Diagnostics, https://www.altona-diagnostics.comExternal Link). For detected C. difficile, we performed strain typing by using high-resolution capillary gel-based PCR ribotyping according to the method previously described by Stubbs et al. (15).

Outcomes

We calculated reported and measured rates of detected toxigenic C. difficile per 10,000 patient bed-days across participating institutions. We compared differences in testing algorithms for detection of toxigenic C. difficile across institutions in Switzerland and performance characteristics of diagnostic algorithms. We considered the proportion of missed toxigenic C. difficile cases and ribotype distributions as additional outcomes. We further assessed the proportion of laboratories using optimized C. difficile diagnostic tests, which we defined as using an algorithm recommended by the European Society of Clinical Microbiology and Infectious Diseases (16).

Statistical Analyses

We separately calculated rates for each diagnostic algorithm performed in the coordinating center laboratory. In addition, we separately calculated rates for dedicated children’s hospitals. We defined missed C. difficile cases as those in which tests were negative at the participating hospital’s laboratory but positive at our institution. We used descriptive statistics to report ribotypes and differences in diagnostic algorithms across all participating institutions. All analyses were performed in Stata version 15.1 (StataCorp, https://www.stata.comExternal Link).

Results

Figure 1. Distribution of centers participating in a prevalence study comparing molecular and toxin assays for nationwide surveillance of Clostridioides difficile, Switzerland. Red circles represent the location of participating centers.

Participating institutions included 76/85 (89.4%) institutions belonging to the Swissnoso network. Among participating institutions, 5 were academic teaching hospitals, 3 were dedicated children’s hospitals, and 36 were affiliated microbiology laboratories. Participating institutions were distributed across all geographic regions of Switzerland (Figure 1).

Participating institutions reported collecting a fecal sample for microbiological workup in »65% (SD +25%) of all patients with hospital-onset diarrhea. Among participating institutions, 15/76 (19.7%) did not begin CDI treatment before fecal sample collection. Among institutions that initiated treatment before collecting fecal samples, 23/76 (30.3%) began treatment in <2% of patients, 12/76 (15.8%) began treatment in 3%–5% of patients, 8/76 (10.5%) began treatment in 6%–10% of patients, and 1 (1.3%) began treatment in 11%–20% of patients. The other 17 (22%) institutions were not able to provide an estimate of these data.

Overall, 354 stool samples were submitted to the coordinating center, of which 338 were eligible for study inclusion; 16 samples were excluded because they were not liquid, their submitted data were incomplete, or they were duplicate samples from 1 patient. Among 338 samples included, 250 were collected as part of the point-prevalence study. We excluded 8 of these because the samples were collected from patients <1 year of age. In all, we included 242 samples in the point-prevalence study.

Diagnostic Algorithms

Figure 2. Testing algorithms at the 36 laboratories participating in a prevalence study comparing molecular and toxin assays for nationwide surveillance of Clostridioides difficile, Switzerland. EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic…

Among the 36 participating laboratories, 1 routinely tested all diarrheal stool samples for toxigenic C. difficile and 35 tested only if a specific test was requested. Optimized diagnostic tests for detection of toxigenic C. difficile were used by 58% (21/36) of laboratories in the winter sampling period and by 61% (22/36) in the summer sampling period. Among laboratories not following the recommendations of the European Society of Clinical Microbiology and Infectious Diseases (16), 9 in the winter sampling period and 10 in the summer sampling period used a nucleic acid amplification test (NAAT) alone, and 5 in the winter sampling period and 3 in the summer sampling period used EIAs for A and B toxins either as a standalone test or as an initial screening test. Only 1 laboratory reported having established PCR ribotyping methodologies (Figure 2).

Point-Prevalence Analyses

We collected demographic characteristics of patients whose stool samples tested positive by our testing algorithms (Table 1). C. difficile tests were required and performed for 68% (165/242) of stool samples; 6% (27/165) were reported as positive by the affiliated microbiology laboratory.

At the coordinating center, we detected C. difficile in 9% (21/242) of samples by EIA for GDH and A and B toxins and in 12% (30/242) of samples by PCR alone. Among all 27 samples reported as positive by the participating centers, we confirmed 18 (67%) by EIA and 24 (89%) by PCR. Among 138 samples reported as negative by the participating centers, 1 (1%) sample tested positive by EIA and 3 (2%) tested positive by PCR at the coordinating center. Among 77 samples not tested for C. difficile at the participating centers, we detected C. difficile in 2 (3%) by EIA and in 3 (4%) by PCR. Among 21 stool samples that tested positive by EIA at the coordinating center, a C. difficile test was not requested in 2 (10%) cases. Among 30 samples that tested positive by PCR at the coordinating center, a C. difficile test was not requested in 3 cases (10%; Table 2).

Measured detection and testing rates of toxigenic C. difficile were higher than the reported rates across all participating institutions (Table 3). Depending on the diagnostic algorithm applied, the largest difference in prevalence across all institutions was measured during the winter sampling period, which had a prevalence of 6.4 cases/10,000 patient bed-days by EIA and 11.4 cases/10,000 patient bed-days by PCR alone. Thus, across all institutions, rates of toxigenic C. difficile detection by PCR alone were <80% higher than detection rates by EIA for GDH and A and B toxins. In addition, detection rates by PCR alone were <100% higher in dedicated children’s hospitals (Table 3).

Ribotype Distribution

Figure 3. Distribution of PCR ribotypes among 107 samples collected in a prevalence study comparing molecular and toxin assays for nationwide surveillance of Clostridioides difficile, Switzerland. *Unknown ribotype.

We cultured and ribotyped 107 toxigenic C. difficile strains, 29 from the 2 point-prevalence days and 78 collected <1 week before each prevalence day. We identified a large diversity of C. difficile ribotypes, 23 (22%) had not been referenced before. The ribotypes most commonly identified included RT014 (12/107; 11%), presumably hypervirulent RT078 (9/107; 8%), RT001 (7/107; 7%), and RT002 (7/107; 7%) (Figure 3).

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Discussion

In this nationwide multicenter study, we found that PCR as a stand-alone test increased reported C. difficile prevalence rates <80% compared with a 2-stage EIA-based algorithm. At first glance, this finding was not surprising given the higher sensitivity of EIA (16). However, the fact that our results and conclusions are based on a nationwide cohort representing all geographic regions of Switzerland adds to the study’s credibility. In addition, our results strengthen the advice of the European Society of Clinical Microbiology and Infectious Diseases study group for C. difficile against use of a single commercial test for diagnosing CDI because of the low positive predictive values when CDI prevalence is low, 46% at a CDI prevalence of 5% (16). However, CDC and ECDC protocols for CDI surveillance define a case of CDI as the combination of diarrheal stool and a positive PCR (12,13). In addition, the clinical practice guidelines for CDI in adults and children published by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America recommend testing by different approaches, such as multistep algorithms or NAAT, depending on the degree of clinical suspicion (17). Based on a systematic review and meta-analysis, the American Society of Microbiology also recommends different approaches, including NAAT-only testing, and algorithms that include GDH and NAAT or GDH, toxins, and NAAT (18). Although these recommendations stand to reason for detection of CDI in individual patients, our results challenge their utility for meaningful comparisons in surveillance studies and suggest that uniform definitions should be provided.

On both point-prevalence days, we noted a higher nationwide rate of toxigenic C. difficile than previously reported in incidence studies performed at different institutions in Switzerland (1921). Our findings suggest that CDI rates have increased during the last decade in Switzerland, a finding that is in line with reports from other countries in Europe (11). Using the same diagnostic algorithm, diagnostic test, and a similar study design to the multicenter point-prevalence study of CDI in hospitalized patients with diarrhea in Europe, the nationwide mean prevalence rates are comparable in Switzerland (mean 6.1 cases/10,000 patient bed-days) and Europe (7.0 cases/10,000 patient bed-days) (11). Because we only included liquid stools in our study, our mean prevalence rate of 9.3 cases/10,000 patient bed-days measured by PCR fulfills the ECDC case definition and further shows that CDI is increasing substantially nationwide.

We found a lower proportion of missed detection of toxigenic C. difficile in Switzerland (9.5%), driven by the absence of clinical suspicion, compared with Europe (23%), which equates to 1 missed case of C. difficile per day among the included institutions in Switzerland. False-negative testing accounted for 1 additional missed diagnosis during both point-prevalence days, which extrapolates to »550 missed cases of C. difficile per year among hospitals across the nation.

We detected a variety of different RTs during our study period, 21% of which had not been referenced before. Of note, we did not recover hypervirulent RT027, but RT078 was the third most common strain circulating in Switzerland during our study. In contrast, a point-prevalence study in Europe identified RT027 as the most commonly circulating strain during its study period but did not detect RT078. RT078 has been associated with similarly severe disease manifestations as RT027, but RT078 has been reported to affect younger patients and to be linked more commonly with community-associated disease in the Netherlands (22). RT078 has been isolated from piglets with diarrhea, possibly suggesting ongoing transmission by introduction to the food chain because isolates from humans and pigs were found to be highly genetically related (22). A component of RT078 infections also was reported in Northern Ireland, which has a large pig population and »1:1 ratio of cattle to humans (23). In Switzerland, RT078 has been isolated previously from 6 wastewater treatment plants, suggesting its dissemination in the community (24). Except for both hypervirulent RT027 and RT078, we identified other similarities in RT distribution between Switzerland and the rest of Europe; RT014, RT001, RT002, and RT020 were among the 10 most commonly identified ribotypes in both settings.

Our study has some limitations, most of which are intrinsic to point-prevalence studies. First, our study only reflects frequency of toxigenic C. difficile detected on 2 days in 2015; therefore, we cannot draw solid conclusions regarding incidence. We expanded the timeframe for assessing the distribution of ribotypes circulating in Switzerland by an additional week for each prevalence day, but this still represents a limited collection of the true incidence. Second, we cannot rule out introduction of bias to testing policies at the participating hospitals, which might have increased testing on the 2 point-prevalence days. However, we did not provide any promotional information regarding our study, so alterations in daily clinical practice among treating physicians is unlikely on these 2 days. Third, we only included liquid stool samples for analyses, but we did not consider any other preanalytical factors, such as the use of laxatives, for testing eligibility. Finally, we applied surveillance definitions recommended by CDC and ECDC rather than defintions used for the clinical diagnosis of CDI in individual patients, such as detection of C. difficile in the context of symptoms related to CDI. Therefore, we cannot rule out detection of toxigenic C. difficile from colonization rather than infection in some cases.

In conclusion, this nationwide multicenter study reveals that PCR as a stand-alone test results in an increase of C. difficile prevalence rates of <80% compared with a 2-stage EIA-based algorithm. Our findings underscore the need for consistent testing algorithms for meaningful interinstitutional and nationwide comparisons. Our results also challenge the utility of the current CDC and ECDC case definitions and highlight the need for uniform recommendations on diagnostic approaches.

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Dr. Widmer is head of the infection control program at University Hospital Basel, University of Basel, Switzerland. His research interests include all aspects of Clostridioides difficile and the epidemiology and prevention of hospital-acquired infections.

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Acknowledgments

We acknowledge and thank the ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study group for C. difficile (ESGCD) for professional support. We also thank all participating centers and laboratories (Appendix).

Astellas Pharmaceuticals Europe provided financial support for this study. The funder did not influence the study design and did not contribute to data collection, data analysis, data interpretation, or writing of the report. Astellas Pharma Europe reviewed the report for factual accuracy before submission, in line with the terms of the funding agreement. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication. Alere provided C. DIFF QUIK CHEK COMPLETE test kits for conducting EIAs to detect GDH and toxins A and B.

The authors declare the following possible conflicts of interest: A.W. is a member of the Astellas and Merck Sharp & Dohme Corp. advisory boards for C. difficile and reports grants from the Swiss National Science Foundation. S.T.-S. is a member of the Astellas and Merck Sharp & Dohme Corp. advisory boards for C. difficile and reports grants from the Swiss National Science Foundation (grant nos. NRP72 and 407240_167060), the Gottfried und Julia Bangerter-Rhyner Stiftung, and the Fund for the Promotion of Teaching and Research of the Voluntary Academic Society, Base

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Cite This Article

DOI: 10.3201/eid2610.190804

Original Publication Date: September 09, 2020

 

Resource:  https://wwwnc.cdc.gov/eid/article/26/10/19-0804_article

Early Results From the CDC Prevention’s Emerging Infections Program shows a decline in Clostridium difficile Infections from 2011 to 2014

The early results from the CDC’s Prevention’s Emerging Infections Program show prevalence steadily increased from 2000 to 2010 but decreased from 2011 to 2014, which is around the time antimicrobial stewardship programs were being introduced because of increased awareness of the disease. For example, the VA introduced their program in 2012.

 

Clostridium difficile rates are dropping for the first time in a decade in healthcare settings, and it’s likely due to better cleaning and antibiotic prescribing policies, authorities say.

The rates for national healthcare incidence of the disease may be decreasing anywhere from 9% to 15%, a Centers for Disease Control and Prevention expert said in an NPR report.

Clostridium difficile rates are dropping for the first time in a decade in healthcare settings, and it’s likely due to better cleaning and antibiotic prescribing policies, authorities say.

The rates for national healthcare incidence of the disease may be decreasing anywhere from 9% to 15%, a Centers for Disease Control and Prevention expert said  in an NPR report.

The decreased rates may be credited to an increase in antimicrobial stewardship programs.

The programs restrict unnecessary antibiotic prescriptions, in addition to implementing stricter cleaning and infection control protocols. C. diff does not respond to conventional cleaning methods.

“It was estimated that C. diff infection was the most commonly reported infection [acquired in healthcare settings] nationally,” said Alice Guh, M.D., medical officer at the CDC. “That generated a lot of awareness.”

That’s three times what it was in 2000.

In nursing homes, 20% to 50% of residents can be colonized with the disease at a time, medical experts note.

To read article in its entirety click on the following link

http://www.mcknights.com/news/c-diff-rates-in-healthcare-settings-drop-for-first-time-in-a-decade/article/672543/

Contagion Live Infectious Diseases Today Report 2017 SHEA’s Spring Conference

for Read the Article In Its Entirety Please Click On the Following Link:

Healthcare-associated infections (HAIs) continue to plague hospitals and long-term care facilities across the country, although, a recent report from shows that strategies to prevent these infections have made progress in decreasing their incidence since 2010. Still, the Centers for Disease Control and Prevention (CDC) has stated that a least one healthcare-associated infection is reported in about one in 25 hospitals on any given day.

When it comes to keeping up on the latest news regarding these harmful infections, the newest strategies being used to prevent them, antimicrobial stewardship efforts, and treating infections caused by organisms that have managed to develop resistance to current antibiotics, the annual Society for Healthcare Epidemiology of America (SHEA) Spring Conference is a gold mine packed full of information from key opinion leaders in the field, and Contagion® will be reporting on the conference for the second year in a row.

Since our inception in February 2016, Contagion® has kept readers current on new findings pertaining to healthcare-associated infections. Two of the big culprits that are most commonly behind these harmful and costly infections are Clostridium difficile and Staphylococcus aureus.

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At last year’s SHEA Conference, we interviewed Robin Jump, MD, PhD, about the burden of C. difficile in the hospital setting and up-and-coming prevention methods that healthcare providers can use to help manage these infections.

– See more at: http://www.contagionlive.com/news/contagion-to-report-on-2017-shea-spring-conference#sthash.kxaDnByE.dpuf

Antibiotic Resistance IS A Serious Global Health Concern

A Nevada woman has died from an infection resistant to all available antibiotics in the United States, public health officials report.

According to the Centers for Disease Control and Prevention, the woman’s condition was deemed incurable after being tested against 26 different antibiotics.

Though this isn’t the first case of pan-resistant bacteria in the U.S., at this time it is still uncommon. Still, experts note that antibiotic resistance is a growing health concern globally and call the newly reported case “a wake up call.”

“This is the latest reminder that yes, antibiotic resistance is real,” Dr. James Johnson, a professor specializing in infectious diseases at the University of Minnesota Medical School, told CBS News. “This is not some future, fantasized armageddon threat that maybe will happen after our lifetime. This is now, it’s real, and it’s here.”

According to the report, the woman from Washoe County was in her 70s and had recently returned to America after an extended trip to India. She had been hospitalized there several times before being admitted to an acute care hospital in Nevada in mid-August.

Doctors discovered the woman was infected with carbapenem-resistant Enterobacteriaceae (CRE), which is a family of germs that CDC director Dr. Tom Frieden has called “nightmare bacteria” due to the danger it poses for spreading antibiotic resistance.

The woman had a specific type of CRE, called Klebsiella pneumoniae, which can lead to a number of illnesses, including pneumonia, blood stream infections, and meningitis. In early September, she developed septic shock and died.

The authors of the report say the case highlights the need for doctors and hospitals to ask incoming patients about recent travel and if they have been hospitalized elsewhere.

Other experts say it underscores the need for the medical community, the government and the public to take antibiotic resistance more seriously.

According to the CDC, at least two million people become infected with antibiotic resistant bacteria each year, and at least 23,000 die as a direct result of these infections.

The World Health Organization calls antibiotic resistance “one of the biggest threats to global health.”

A grim report released last year suggests that if bacteria keep evolving at the current rate, by 2050, superbugs will kill 10 million people a year.

While scientists are working to develop new antibiotics, that takes time, and experts encourage doctors and the public to focus on prevention efforts.

One of the most important ways to prevent antibiotic resistance is to only take antibiotics only when they’re necessary.

“Drug resistance like this [case] generally develops from too much exposure to antibiotics,” assistant professor of pediatrics at Johns Hopkins University School of Medicine and director of the Pediatric Antimicrobial Stewardship Program at The Johns Hopkins Hospital, told CBS News. “Every time you’re placed on an antibiotic it’s important to question if it’s absolutely necessary and what’s the shortest amount of time you can take this antibiotic for it to still be effective.”

Johnson notes that medical tourism – the practice of traveling to another country to obtain medical treatment, typically at lower cost – may no longer be worth the risk. “With this [antibiotic] resistance issue, the risk/benefit of this approach really changes and I think that people really need to be aware and seriously consider if it’s a good idea given the possibility of this kind of thing,” he said.

Frequent hand washing, particularly in healthcare settings, is also extremely important in preventing the spread of germs.

To read the article in its entirety please click on the link below to be redirected:

http://www.lasvegasnow.com/news/nevada-woman-died-from-superbug-resistant-to-all-available-antibiotics-in-us/640548775

Centers for Disease Control and Prevention (CDC) Provides 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.

THE GOOD NEWS
The Center for Infectious Disease Research and Policy (CIDRAP) recently -hospital-stewardship-lowers-antibiotic-use-infections”>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.”

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.

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.”

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.

 

 

To read article in its entirety click on the link below:

 http://www.hcplive.com/medical-news/latest-news-and-updates-on-c-difficile-infection-management-and-treatment/P-4#sthash.iDm6FgAP.dpuf

 

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