Tag Archives: Clostridium difficile prevention

U.S. Food and Drug Administration Released Notice For Hospital Mattress Safety

Health care facilities everywhere have been ramping up their disinfection practices in order to prevent the spread of infectious diseases. However, when it comes to hospital mattresses, one of the biggest vectors for spreading deadly bugs, efforts are still falling short.

With health care workers using chemicals that are intended for dry surfaces, the mattresses are harboring pathogens such as Clostridium difficile (C. diff), and, as Edmond A. Hooker, MD, DrPH, professor in the Department of Health Administration at Xavier University, pointed out at the 5th Annual International C. diff Awareness & Health Expo, regulatory agencies seem to have “turned a blind eye” to the issue.

Until now.

The US Food and Drug Administration (FDA) recently released a notice on how to keep hospital mattress covers safe.

In this notice, the FDA notes safety concerns regarding hospital mattress covers, particularly that over time they can “wear out and allow blood and body fluids to penetrate and get trapped inside mattresses.” They added, “If blood or body fluids from one patient penetrate and get absorbed in a mattress, the fluids can leak out the next time the mattress is used.” If that happens, the next patient runs the risk of coming into contact with these fluids, and thus, becoming infected with pathogens from the bed’s previous occupants.

The FDA reports that this is not the first time they acknowledged these concerns; they released a safety communication in 2013 to make health care workers aware of the issue. However, the problem of contaminated hospital mattresses persists.

“There is no question there has been report after report after report of, ‘We had this outbreak. We killed all these people.’ There was just a report that came out on 18 people who were sick in a French hospital; they were on beds manufactured here in America, and 4 people were killed before they finally realized that it was the mattresses. They took all of the mattresses out of service and stopped the outbreak,” Dr. Hooker told Contagion ® in an exclusive interview.

“There’s a reason that it’s an under reported problem; hospitals don’t want to say, ‘Hey, we just killed a bunch of people. We kill 29,000 people a year with C. difficile infections. Do you hear that? I mean, that’s like crashing a plane every day and we do nothing about it. We just act like it didn’t happen.”

In an effort to address the issue, the FDA has released recommendations based on Centers for Disease Control and Prevention (CDC) guidelines for environmental infection control in health care facilities; they include:

  1. Develop an inspection plan for all hospital mattresses and mattress covers in the facility. Learn the time of life for all mattresses/mattress covers by checking the manufacturer’s guidelines; follow any other recommendations that the manufacturers list. If you have any additional questions, contact the mattress manufacturer.
  2. Inspect each hospital mattress for visible signs of damage, which can include: cuts, tears, cracks, pinholes, snags, or stains. On a routine basis, remove mattress covers and check the inside. With the cover removed, check the mattress for wet spots, staining, or other signs of damage. Be sure to check all sides of the mattress as well as underneath. You will not be able to effectively inspect the mattress with the cover on.
  3. Remove any mattresses that are damaged, appear worn, or are visibly stained and immediately replace any mattress covers that are damaged.
  4. Maintain your mattresses and mattress covers by cleaning and disinfecting them “according to the manufacturer’s guidelines.” DO NOT stick needles into the hospital mattress through the cover, the FDA stresses.

“The FDA notice about mattress failures is an important first step. However, much more needs to be done. Most failures are not being reported to FDA, and the 700 reports that they have represents an industry-wide problem. Up to one-third of hospital mattresses currently in service in hospitals have failed. Also, the ones that have not failed are not being cleaned,”

Dr. Hooker stressed to Contagion ® in a follow-up interview. “These mattresses quickly get fissures and microscopic cracks that allow bacteria to remain on the surface during terminal cleaning. The next patient is then exposed to those bacteria and gets a hospital-acquired infection. The CDC needs to mandate better cleaning practices nationwide, which they can do.

The CDC needs to also mandate inspection of every mattress after every patient. Damaged mattresses should be removed from service immediately.”

 

To review the article in its entirety, please click on the link below to be re-directed:

http://www.contagionlive.com/news/fda-acknowledges-hospital-mattresses-as-hotbed-for-germs-releases-recommendations

SYN-004 (ribaxamase) For C. difficile Prevention Advances; U.S. Food and Drug Administration (FDA) Has Granted A Breakthrough Therapy Designation

On May 11, 2017 Synthetic Biologics, Inc. a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients, announced that the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Therapy Designation for SYN-004 (ribaxamase) for the prevention of Clostridium difficile infection.

SYN-004 (ribaxamase) is the Company’s first-in-class oral enzyme designed to protect the gut microbiome from disruption caused by certain intravenous (IV) beta-lactam antibiotics.

The Breakthrough Therapy Designation is based on data from the successful Phase 2b clinical trial of ribaxamase, which met its primary endpoint of significantly reducing CDI. FDA Breakthrough Therapy Designation is intended to expedite development and review timelines when preliminary clinical evidence indicates that a drug may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for serious or life threatening diseases. If approved by the FDA, SYN-004 (ribaxamase) would be the first available drug designed to prevent Clostridium difficile infection by protecting the gut microbiome from antibiotic-mediated dysbiosis.

“We are delighted by the FDA’s recognition of ribaxamase’s potential to prevent CDI, and the dire need to fill the current void of an approved intervention,” said Jeffrey Riley, President and Chief Executive Officer. “Following this announcement, we have been asked and anticipate requesting a Type-B multidisciplinary meeting with the Agency for a comprehensive discussion on the overarching, high-level drug development plan and pathway to licensure for ribaxamase. We look forward to working closely with the FDA throughout the development and review process and remain dedicated to bringing this potentially paradigm-shifting approach to antibiotic therapy to patients in critical need.”

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Protecting the Gut Microbiome: A Paradigm Shift in Managing GI Disorders

Live Broadcast On Tuesday, May 16th Join us with our guest, Dr. Joseph Sliman, MD, MPH, Chief Medical Officer of Synthetic Biologics.  Dr. Sliman will be discussing  the protection of the natural gut microbiome from the unintended consequences of intravenous (IV) antibiotics which are excreted into the gut is expected to protect against opportunistic enteric infections. Synthetic Biologics is developing two microbiome-focused drug candidates in Phase 3 development including, SYN-004 (ribaxamase) which is designed to protect the gut microbiome by degrading certain IV beta-lactam antibiotics for the prevention of Clostridium difficile infection (CDI), pathogenic
overgrowth and the emergence of antimicrobial resistance, and SYN-010 which is intended to reduce the impact of methane producing organisms in the gut microbiome to treat an underlying cause of irritable bowel syndrome with constipation (IBS-C).

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To learn more about Synthetic Biologics, please click on the link provided below

.http://www.syntheticbiologics.com/about/overview

Source:  Synthetic Biologics

Synthetic Biologics – Protecting the Gut Microbiome: A Paradigm Shift in Managing GI Disorders

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.”

Recurrent Clostridium difficile (C.diff.) Bezlotoxumab For the Prevention of Recurrent CDI

Abstract Published: 2017 Jan 26

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection.

 

Recurrent Clostridium difficile Prevention

Wilcox MH1, Gerding DN1, Poxton IR1, Kelly C1, Nathan R1, Birch T1, Cornely OA1, Rahav G1, Bouza E1, Lee C1, Jenkin G1, Jensen W1, Kim YS1, Yoshida J1, Gabryelski L1, Pedley A1, Eves K1, Tipping R1, Guris D1, Kartsonis N1, Dorr MB1; MODIFY I and MODIFY II Investigators.
Author information
Abstract

Background Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy.

Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively.

Methods –  We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis.

The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population.

Results In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome.

The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively.

The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea.

Conclusions Among participants receiving antibiotic treatment for primary or recurrent
C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo.

The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).
Also Resource:

https://www.ncbi.nlm.nih.gov/pubmed/28121498

Bezlotoxumab – A New Agent for Clostridium difficile Infection. [N Engl J Med. 2017]

Bridging Collaboration Between Patients and Healthcare Providers to Reduce Hospital-Acquired Infections

C. diff. Spores and More” Global Broadcasting Network
will host a special episode on their live radio program (cdiffradio.com)
airing on Tuesday, January 24, 2017 at 1:00 pm EST featuring world-renowned
infectious disease expert, Dr. Hudson Garrett Jr., Global Chief Clinical Officer for Pentax Medical-Hoya Corporation and Chairperson of the Clinical Education Committee
for the C Diff Foundation.

This special episode, Bridging Collaboration Between Patients and Healthcare Providers to Reduce Hospital-Acquired Infections (HAI’s),  will feature a robust discussion on the patient’s role in preventing healthcare associated infections, an overview of medical device hygiene and infection control, the importance of antibiotic stewardship, and applications of evidence-based infection control measures across the entire healthcare continuum of care.

“Healthcare continues to become more and more complex as the acuity and needs of the patient changes along with the correlating technologies. Patients and Healthcare Providers must work together to mitigate the risk for Healthcare Associated Infections and other adverse events,” says Dr. Garrett.

C. diff. Spores and More “ spotlights world renowned topic experts, research scientists, healthcare professionals, organization representatives, C. diff. survivors, board members, and their volunteers who are all creating positive changes in the
C. diff.
community and more.

Through the interviews, the C Diff Foundation’s mission connects, educates, and empowers listeners worldwide.

Questions received through the show page portal will be reviewed and addressed  by the show’s Medical Correspondent, Dr. Fred Zar, MD, FACP,  Dr. Fred Zar is a Professor of Clinical Medicine, Vice Head for Education in the Department of Medicine, and Program Director of the Internal Medicine Residency at the University of Illinois at Chicago.  Over the last two decades he has been a pioneer in the study of the treatment of Clostridium difficile disease and the need to stratify patients by disease severity.

 

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