Tag Archives: C. diff. prevention

Clostridium difficile Vaccines In Trials Reviewed by Larry K. Kociolek, MD and Stanford T. Shulman, MD

CDI is not only observed in hospitalized patients and patients with antibiotic exposure but also in populations previously thought to be at low risk, such as healthy young adults and children. Community-associated CDI has also emerged as an important cause of diarrheal illness.4,5 The spectrum of CDI ranges from asymptomatic carriage and mild diarrhea to life-threatening pseudomembranous colitis, toxic megacolon, and fulminant colitis potentially requiring urgent colectomy.4-6 Furthermore, long-term resolution of symptoms is difficult to achieve in a large percentage of patients with CDI; approximately 20% of patients with CDI experience recurrent infection after responding to initial therapy.2

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

http://www.infectiousdiseaseadvisor.com/clostridium-difficile/status-of-clostridium-difficile-vaccines/article/646015/

Although the pathophysiology of CDI is complex and multifactorial, toxin B (TcdB), a cytotoxin, is now thought to be the primary mediator of symptomatic infection. Toxin A (TcdA) and binary toxin (in particular strains such as epidemic strain BI/NAP1/027) are also likely to do so, but the extent to which they contribute to disease is unclear.5 A mature and varied intestinal microbiome confers resistance to colonization by C difficile, protecting against CDI.6 Thus, exposure to C difficile spores alone is rarely sufficient to cause CDI, while perturbation of the microbiome following antibiotic exposure permits C difficile spores to colonize, germinate, and release toxins that induce CDI symptoms.

Antibodies to TcdA and TcdB mediate protection against primary CDI and recurrences. High serum antitoxin levels, especially immunoglobulin G (IgG) antitoxin A, are associated with asymptomatic colonization and protection against CDI recurrence.7

Bezlotoxumab, a monoclonal antibody against TcdB recently approved by the US Food and Drug Administration (FDA), reduces the rate of CDI recurrence in adults.8 However, the protective effect of this passive immunization strategy is short-lived.

Vaccines appear to be a promising intervention that provides long-term protection against CDI episodes, and several are in various stages of development.6 There are 3 candidate vaccines currently undergoing phase 2 and 3 clinical evaluation for CDI prevention.6

The Sanofi Pasteur toxoid vaccine uses formalin-inactivated full-length TcdA and TcdB administered by intramuscular injection at days 0, 7, and 30. In phase 2 trials, the vaccine was safely administered to adults older than 50, and seroconversion to TcdA and TcdB was 97% and 92%, respectively.9 The high-dose adjuvanted vaccine, which is currently being evaluated in a phase 3 clinical trial, has demonstrated elevated circulating titers for up to 3 years after the last dose of the primary series given at 0, 7, and 30 days.10

Pfizer is currently evaluating a genetically modified and chemically treated recombinant full-length TcdA and TcdB vaccine in a phase 2 trial. In a phase 1 trial with 3 different dosages given as a 3-dose schedule in adults 50 to 85 years old, satisfactory immunogenicity and safety were demonstrated for both the aluminum hydroxide-adjuvanted and non-adjuvanted vaccine.11 Best responses were observed with the non-adjuvanted formulation, and there were no differences in responses in 50- to 64 year-old and 65- to 80 year-old subjects.

Valneva, an Austrian pharmaceutical company, is developing VLA84, a genetic fusion of the truncated cell-binding domains of TcdA and TcdB that is purported to be less complex to produce and purify compared with the toxoid vaccines. In a phase 1 trial, VLA84 was shown to be highly immunogenic in adults and the elderly without serious adverse effects.12 A phase 2 clinical trial has been completed, but data are not yet available.

All 3 of these parenteral candidate vaccines are moving forward in development and appear promising for the prevention of symptomatic CDI. An oral mucosal vaccine using a genetically engineered Bacillus subtilis vector is also in development.13 Because host immune response against non-toxin antigens may additionally protect against colonization and subsequent transmission, an alternative possibility of developing vaccines against surface proteins that prevent C difficile mucosal adherence and colonization is attractive. To this end, a number of surface-associated antigens including flagellar proteins, S-layer proteins, proteases, and complex polysaccharides have been studied in animal models as possible vaccine candidates.14

Larry K. Kociolek, MD, is the associate medical director of Infection Prevention and Control at The Ann & Robert H. Lurie Children’s Hospital of Chicago and assistant professor of Pediatrics at the Northwestern University Feinberg School of Medicine in Illinois.

Stanford T. Shulman, MD, is the medical director of Infection Prevention and Control at The Ann & Robert H. Lurie Children’s Hospital of Chicago and Virginia H. Rogers Professor of Pediatric Infectious Disease​ at the Northwestern University Feinberg School of Medicine​ in Illinois.

References

  1. Magill SS, Edwards JR, Bamberg W, et al; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198-1208. doi:10.1056/NEJMoa1306801
  2. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372:825-834. doi:10.1056/NEJMoa1408913
  3. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55 Suppl 2:S88-S92. doi:10.1093/cid/cis335
  4. Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med. 2013;173:1359-1367. doi:10.1001/jamainternmed.2013.7056
  5. Kelly CP, Lamont JT. Clostridium difficile–more difficult than ever. N Engl J Med. 2008;359:1932-1940. doi:10.1056/NEJMra0707500
  6. Kociolek LK, Gerding DN. Breakthroughs in the treatment and prevention of Clostridium difficile infections. Nat Rev Gastroenterol Hepatol. 2016;13:150-160. doi:10.1038/nrgastro.2015.220
  7. Kelly CP, Kyne L. The host immune response to Clostridium difficile. J Med Microbiol. 2011;60:1070-1079. doi:10.1099/jmm.0.030015-0
  8. Wilcox MH, Gerding DN, Poxton IR, et al; MODIFY I and MODIFY II Investigators. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-317. doi:10.1056/NEJMoa1602615
  9. de Bruyn G, Saleh J, Workman D, et al; H-030-012 Clinical Investigator Study Team. Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: A randomized phase 2 clinical trial. Vaccine. 2016;34:2170-2178. doi:10.1016/j.vaccine.2016.03.028
  10. de Bruyn G, Glover R, Poling TL, et al. Three year follow up for safety and immunogenicity of a candidate Clostridium difficile toxoid vaccine. Presented at: IDWeek 2016. New Orleans, Louisiana; October 26-30, 2016. Poster 746.
  11. Sheldon E, Kitchin N, Peng Y, et al. A phase 1, placebo-controlled, randomized study of the safety, tolerability, and immunogenicity of a Clostridium difficile vaccine administered with or without aluminum hydroxide in healthy adults. Vaccine. 2016;34:2082-2091. doi:10.1016/j.vaccine.2016.03.010
  12. Bezay N, Ayad A, Dubischar K, et al. Safety, immunogenicity and dose response of VLA84, a new vaccine candidate against Clostridium difficile, in healthy volunteers. Vaccine. 2016;34:2585-2592. doi:10.1016/j.vaccine.2016.03.098
  13. Permpoonpattana P, Hong HA, Phetcharaburanin J, et al. Immunization with Bacillus spores expressing toxin A peptide repeats protects against infection with Clostridium difficile strains producing toxins A and B. Infect Immun. 2011;79:2295-2302. doi:10.1128/IAI.00130-11
  14. Ghose C, Kelly CP. The prospect for vaccines to prevent Clostridium difficile infection. Infect Dis Clin North Am. 2015;29:145-162. doi:10.1016/j.idc.2014.11.013
DISCLAIMER
“The C Diff Foundation’s mission is to educate and advocate for Clostridium difficile infection prevention, treatments, support, and environmental safety worldwide.
 
The C Diff Foundation’s organization is comprised of 100% volunteering members who are dedicated to our mission and adhere to the Foundation’s Code of Ethics
which prohibits the endorsement and promotion of products, services, medications, or clinical studies in progress. 
 
All website entries, public presentations, and workshops are to raise C. diff. infection awareness in all areas of the C Diff Foundation’s mission statement, including infection prevention, sepsis, healthcare-associated infections, antimicrobial resistance, antibiotic stewardship and provide education on all the above.”

C. diff. and Clorox Bleach Germicidal Cleaners and Wipes Update

Now there’s one C. diff contact time for CLOROX entire Bleach Germicidal lineup.  CLOROX Bleach Germicidal Cleaners and Wipes update  October 13, 2016 *
  CLOROX improved disinfection claims across their full portfolio of Bleach Germicidal Cleaners and Wipes. In fact, now they’re all EPA-registered to kill C. diff in just 3 minutes.
Clorox Professional Products Company
Here’s what’s new.*
One C. diff contact time for both Wipes and Cleaners:
Now our entire Bleach Germicidal line kills C. diff in 3 minutes, to simplify your infection control protocols.
Now EPA-registered to kill outbreak-causing viruses:
Enterovirus D68, Influenza A and B viruses, Measles Virus, MERS-CoV, Norovirus and SARS-CoV
Clorox Professional Healthcare Products
Trusted by over 2,000 US hospitals.
CLOROX Bleach Germicidal Cleaners and Wipes make it easier for you to safeguard patient environments against HAI and outbreak-causing pathogens. See why these ready-to use bleach disinfectants are trusted by more than 2,000 US hospitals as part of their infection control protocols.

 

 

*Please note – The C Diff Foundation does not endorse any product and/or clinical study in progress.  All website postings are strictly for informational purposes only.   If there are questions, please contact the company directly.  Thank you.

C. diff. News: A Canadian Acute Care Facility Implemented Intervention To Screen and Isolate Asymptomatic Clostridium difficile Carriers With Noted Decreased Incidence Of Health-Care Associated C. difficile Infection

C. diff. In The News

An intervention at a Canadian acute care facility to screen and isolate asymptomatic Clostridium difficile carriers was associated with decreased incidence of
health-care associated C. difficile infection
, a finding that needs to be confirmed in additional studies, according to a new study published online by JAMA Internal Medicine.

C. difficile infection (CDI) is a major cause of health care-associated infection worldwide.
CDI can cause symptoms from mild diarrhea to life-threatening toxic megacolon. About half a million cases happen each year in the United States, causing 29,000 deaths and creating $4.8 billion in excess medical costs.

Infection control recommendations mainly focus on patients with CDI. But asymptomatic
C. difficile carriers may also play a role in disseminating spores because they can
contaminate the environment and caregivers’ hands, and because they are not detected are not placed under isolation precautions.

Yves Longtin, M.D., of the Jewish General Hospital and McGill University, Montreal, Canada, reports on the effects of the intervention to reduce the incidence of health care-associated CDI (HA-CDI)   at the Quebec Heart and Lung Institute, Quebec City, Canada.

The study, conducted between November 2013 and March 2015, screened patients at admission for the tcdB gene through a rectal swab and those found to be C. difficile carriers were put under contact isolation precautions during their hospitalization.

Among the 7,599 patients who were screened, 368 (4.8 percent) were identified as C. difficile carriers and placed under isolation. During the intervention, the incidence rate of HA-CDI decreased by more than 50 percent to 3.0 per 10,000 patient days compared to 6.9 per 10,000 patient days before the intervention. The authors estimate the intervention prevented approximately 63 cases.

Limitations of the study include the intervention was conducted at a single center and the findings still need to be confirmed in additional studies.

The authors note that the strategy to screen and isolate C. difficile carriers may be cost-effective. The intervention cost $130,000 (U.S.) and prevented 63 cases; the estimated savings from averting CDI cases was greater than the cost of the intervention.

“The intervention is simple and could be easily implemented in other institutions. If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of HA-CDI every year in North America,” the study concludes.

Commentary: Active Surveillance, Isolation of Asymptomatic Carriers of Clostridium difficile at Hospital Admission

“The results of this study are promising for reducing HA-CDI. … Longtin et al have shown the possible benefit of using active surveillance testing and isolation of asymptomatic carriers for preventing HA-CDI. Larger, well-designed studies, such as cluster randomized trials, are ultimately needed to confirm the effectiveness of this strategy,” writes Alice Y. Guh, M.D., M.P.H., and L. Clifford McDonald, M.D., of the Centers for Disease Control and Prevention, Atlanta.

TO ACCESS ARTICLE IN ITS ENTIRETY:

Story Source:

The above post is reprinted from materials provided by The JAMA Network Journals. Note: Materials may be edited for content and length.


Journal References:

  1. Yves Longtin, Bianka Paquet-Bolduc, Rodica Gilca, Christophe Garenc, Elise Fortin, Jean Longtin, Sylvie Trottier, Philippe Gervais, Jean-François Roussy, Simon Lévesque, Debby Ben-David, Isabelle Cloutier, Vivian G. Loo. Effect of Detecting and IsolatingClostridium difficileCarriers at Hospital Admission on the Incidence ofC difficileInfections. JAMA Internal Medicine, 2016; DOI: 10.1001/jamainternmed.2016.0177
  2. Alice Y. Guh, L. Clifford McDonald. Active Surveillance and Isolation of Asymptomatic Carriers ofClostridium difficileat Hospital Admission. JAMA Internal Medicine, 2016; DOI: 10.1001/jamainternmed.2016.1118

Cite This Page:

The JAMA Network Journals. “Effort to detect, isolate asymptomatic C. difficile carriers linked to lower incidence.” ScienceDaily. ScienceDaily, 25 April 2016. <www.sciencedaily.com/releases/2016/04/160425141547.htm

Clostridium difficile (C.diff.) Infection (CDI) Rates In the United States and Across the Globe Have Increased In the Last Decade, Along With Associated Morbidity and Mortality

ahrq-logo-pic

 

 

Early Diagnosis, Prevention, and Treatment of Clostridium difficile: Update

Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
5600 Fishers Lane
Rockville, MD 20857
March 2016

 

Clostridium difficile is a gram-positive, anaerobic bacterium generally associated through ingestion. Various strains of the bacteria may produce disease generating toxins
and TedA and TedB, as well as the lesser understood binary toxin.

Our use of the term indicates this review’s focus is the presence of clinical disease rather than asymptomatic carriage of C. difficile CDI symptoms can range from mild diarrhea to severe cases including pseudomembranous colitis and toxic megacolon and death.

Estimated U.S. health care associated CDI incidence in 2011 was 95.3 per 100,000, or about
293,000 cases nationally. Incidence is higher among females, whites, and persons 65 years of
age or older. (1)

About one third to one half of health-care onset CDI cases begin in long term care,thus residents in these facilities are at high risk.  Incidence rates may increase by four or five-fold during outbreaks.

Community associated CDI, where CDI occurs outside the institutional setting,
is also on the rise, though still generally lower than institution associated rates and may be in part due to increased surveillance. Estimated community associated CDI was 51.9 per 100,000, or   159,700 cases in 2011.  (1)

Community-associated CDI complicates measuring the effectiveness of  prevention within an institutional setting. 3  Additionally, the pathogenesis of CDI is complex and not
completely understood, and onset may occur as late as several months after hospitalization or antibiotic use

The estimated mortality rate for health -care associated CDI ranged from 2.4 to 8.9 deaths per

100,000 population in 2011.(1) For individuals ≥65 years of age, the mortality rate
was 55.1 deaths per 100,000; (1)

CDI was the 17th leading cause of death in this age group (4)
Hypervirulent C. difficile  strains have emerged since 2000 . These affect a wider population

that includes children, pregnant women, and other healthy
adults, many of whom lack standard risk profiles such as previous hospitalization or antibiotic use.(5)

The hypervirulent strains  account for 51 percent of CDI, compared to only 17 percent
of historical isolates. (6)

Time from symptom development to septic shock may be reduced in the hypervirulent strains, making quick diagnosis and proactive treatment regimens critical for positive outcomes.

To read more on  TREATMENT, PREVENTION, KEY QUESTIONS ——

https://www.effectivehealthcare.ahrq.gov/ehc/products/604/2208/c-difficile-update-report-160329.pdf

Early Diagnosis, Prevention, and Treatment of Clostridium difficile: Update

Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
5600 Fishers Lane
Rockville, MD 20857
March 2016

 

Sources:

1Appendix J. References for Appendixes
1.Alcala L, Reigadas E, Marin M, et al.
Comparison of GenomEra C. difficile and Xpert
C. difficile as confirmatory tests in a multistep
algorithm for diagnosis of Clostridium difficile
infection.
J Clin Microbiol 2015 Jan;53(1):332
5. PMID: 25392360.
2.Barkin JA, Nandi N, Miller N, et al.
Super iority
of the DNA amplification assay for the
diagnosis of C. difficile infection: a clinical
comparison of fecal tests.
Dig Dis Sci 2012Oct;57(10):2592-
9. PMID: 22576711.
3.Bruins MJ, Verbeek E, Wallinga JA, et al.
Evaluation of three enzyme immunoassay
s and a loo mediated isothermal amplification test
for the laboratory diagnosis of Clostridium
difficile infection. Eur J Clin Microbiol Infect
Dis 2012 Nov;31(11):3035 9. PMID:
22706512.
4.Buchan BW, Mackey TL, Daly JA, et al.
Multicenter clinical evalu
ation of the portrait
toxigenic C. difficile assay for detection of
toxigenic Clostridium difficile strains in clinical
stool specimens. J Clin Microbiol 2012
Dec;50(12):3932-
6. PMID: 23015667.
5.Calderaro A, Buttrini M, Martinelli M, et al.
Comparative analysis of different methods to
detect Clostridium difficile infection. New
Microbiol 2013 Jan;36(1):57-
63. PMID:
23435816.
6.Carroll KC, Buchan BW, Tan S, et al.
Multicenter evaluation of the Verigene
Clostridium difficile nucleic acid assay.
J ClinMicrobiol 2013 Dec;51(12):4120-
5. PMID:24088862

IDSA and SHEA Release New Antibiotic Stewardship Guidelines

In The News

April 2016

Preauthorization of broad-spectrum antibiotics and prospective review after two or three days of treatment should form the cornerstone of antibiotic stewardship programs to ensure the right drug is prescribed at the right time for the right diagnosis. These are among the numerous recommendations included in new guidelines released by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) and published in the journal Clinical Infectious Diseases.

“Initially, antibiotic stewardship was more focused on cost savings, and physicians responded negatively to that, because they often felt it was best to give patients the newest, most expensive drug,” said Tamar Barlam, MD, lead co-author of the guidelines, director of the antibiotic stewardship program at Boston Medical Center and associate professor of medicine at Boston University Medical School. “While these programs do save hospitals money, their most important benefit is that they improve patient outcomes and reduce the emergence of antibiotic resistance. When we say stewardship, we really mean stewardship, and increasingly, doctors are realizing it’s important and necessary.”

The White House has called for hospitals and healthcare systems to implement antibiotic stewardship programs by 2020 to ensure appropriate use of these vital drugs and reduce resistance, an escalating problem that threatens the ability to effectively treat often life-threatening infections.

The new guidelines replace those originally created to help with the development of programs when antibiotic stewardship was in its infancy, and instead focus on specific strategies that the evidence suggests are most beneficial to ensure the program will be effective and sustainable. They also note it is key that these programs tailor interventions based on local issues, resources and expertise. To ensure that, the guidelines recommend the programs be led by physicians and pharmacists and rely on the expertise of infectious diseases specialists.

“We want hospital administrators to understand the importance of giving antibiotic stewardship their full support to ensure its success,” said Sara Cosgrove, MD, MS, lead co-author of the guidelines, president-elect of SHEA and associate professor of medicine and epidemiology at Johns Hopkins University, and director of the antimicrobial stewardship program and associate hospital epidemiologist at The Johns Hopkins Hospital, Baltimore. “Distributing a few brochures or holding grand rounds won’t do it. It’s vital that antibiotic stewardship be integrated into the hospital’s culture and that infectious disease specialists guide strategies that have been shown to work.”

The guidelines note that more research needs to be done to determine how to ensure antibiotic stewardship is most effective. However, the best evidence to date suggests a number of components, including the following, will help ensure the implementation of an effective antibiotic stewardship program.

  • Preauthorization or prospective audit and feedback – Targeted antibiotics, such as those that treat emerging drug-resistant bacterial infections, should require preauthorization. This means providers need to get approval to use antibiotics before they are prescribed. Prospective audit and feedback can be an alternate strategy or combined with preauthorization. Prospective audit allows antibiotic stewards to engage the prescribing clinician after the antibiotic has been used, typically after two or three days, to optimize antibiotic treatments. Both methods can reduce antibiotic misuse and decrease the development of resistance. Hospitals should choose one or both of these methods as part of their program based on their local resources and expertise.
  • Syndrome-specific interventions – The guidelines recommend focused multifaceted interventions for the treatment of specific syndromes, rather than trying to improve treatment of all infections at once. For example, Dr. Barlam said those leading a hospital’s antibiotic stewardship program might take a close look at management of pneumonia during winter, including making recommendations to shorten the amount of time people are treated and switching to an oral agent more quickly, and then measuring the results of those interventions. In the fall, the program might focus on urinary tract infections and then several months later, switch to skin and soft tissue infections. “This method makes stewardship more manageable and provides a targeted and clear treatment message rather than trying to disseminate 100 different lessons at the same time,” she said.
  • Rapid diagnostic testing – The guidelines note that rapid diagnostic testing of respiratory specimens can help determine if the cause is viral and therefore reduce the inappropriate use of antibiotics. They also note that the rapid testing of blood cultures in addition to conventional culture is helpful, but should be guided by the antibiotic stewardship team for maximum benefit to the patient.

Other recommendations include reducing the use of antibiotics associated with Clostridium difficile infection, implementing antibiotic time-outs and other strategies to encourage prescribers to perform routine reviews of regimens and using computerized clinical decision support if possible.

The guidelines do not recommend relying solely on passive educational materials to implement antibiotic stewardship because any improvement likely will not be sustained. Lectures and brochures should be used to supplement strategies such as antibiotic preauthorization and prospective audit and feedback, the authors note.

AT A GLANCE

  • Preauthorization and prospective review of antibiotics are among the many recommendations to ensure antibiotic stewardship programs are most effective, suggest new guidelines from IDSA/SHEA.
  • Antibiotic stewardship programs should be led by physicians and pharmacists, including ID specialists, who have the expertise and education to ensure the right drug is being prescribed at the right time for the right diagnosis.
  • Antibiotic stewardship programs must be based on the specific problems identified by the healthcare facility and a realistic examination of available resources to ensure interventions are performed with consistency.
  • These programs have been shown to improve patient outcomes, reduce antibiotic resistance and save money.

In addition to Drs. Barlam and Cosgrove, the antibiotic stewardship program guidelines panel includes: Lilian Abbo, Conan MacDougall, Audrey N. Schuetz, Ed Septimus, Arjun Srinivasan, Timothy Dellit, Yngve T. Falck-Ytter, Neil Fishman, Cindy W. Hamilton, Timothy C. Jenkins, Pamela A. Lipsett, Preeti N. Malani, Larissa S. May, Gregory J. Moran, Melinda M. Neuhauser, Jason Newland, Christopher A. Ohl, Matthew Samore, Susan Seo and Kavita K. Trivedi.

IDSA and SHEA individually have published myriad treatment guidelines and together have published several, including the prevention of healthcare-associated infections and antimicrobial prophylaxis in surgery.

As with other IDSA and SHEA guidelines, the antibiotic stewardship guidelines will be available in a smartphone format and a pocket-sized quick-reference edition.

The full guidelines are available free on the

IDSA website at http://www.idsociety.org

 

SHEA website at http://www.shea-online.org.

 

To read this article in its entirety click  on the following link:

http://www.eurekalert.org/pub_releases/2016-04/idso-nas041216.php