Category 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.”

Pfizer’s C.difficile Vaccine Candidate PF-06425090 Will Progress Into Phase 3 Study

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Pfizer Announces Positive Top-Line Results from Phase 2 Study of Investigational
Clostridium difficile Vaccine for the
Prevention of C. difficile Infection

Pfizer’s C. difficile Vaccine Candidate to Commence Phase 3 Study in First Half of 2017

C. difficile is an Increasing Worldwide Concern Associated with Approximately 29,000 Annual Deaths in the U.S. Alone
On Thursday, January 26, 2017 Pfizer Inc. announced that the Phase 2 study
evaluating the Company’s Clostridium difficile (C. difficile) vaccine
candidate, PF-06425090, provided positive data, based on a pre-planned interim analysis.

The randomized Phase 2 study (NCT02561195) examined the safety, tolerability, and immunogenicity of the vaccine in healthy adults 65 to 85 years of age. Pfizer’s vaccine candidate is designed to help prevent C. difficile infection (CDI), which can include life-threatening diarrhea and pseudomembranous colitis,1 by inducing a functional antibody response capable of neutralizing the two main disease-causing toxins produced by
C. difficile (toxins A and B).2

“Despite improved infection control measures, C. difficile disease continues to rise, further augmenting an already urgent public health threat with particular negative impact on older adults,” said Kathrin Jansen, Ph.D., senior vice president and head of Vaccine Research and Development for Pfizer Inc. “We are very encouraged by these interim immunogenicity and safety results demonstrating robust increases in vaccine-elicited neutralizing antibodies to both toxins, that we believe could provide protection against C. difficile disease.”

Based on findings from the pre-planned interim analysis, Pfizer’s C. difficile vaccine candidate will progress into Phase 3 in the first half of 2017.

Pfizer’s C. difficile vaccine candidate was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in August 2014. The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of new drugs and vaccines intended to treat or prevent serious conditions and address an unmet medical need.3 About the Phase 2 Study The Phase 2 study (NCT02561195) was a randomized, placebo-controlled, observer-blinded study of more than 850 healthy adults 65-85 years of age, evaluating the safety, tolerability, and immunogenicity of two dose levels (100 µg and 200 µg) of Pfizer’s C. difficile vaccine candidate on two different three-dose vaccination schedules (Days 1/8/30 and Months 0/1/6). More information about the PF-06425090 Phase 2 study can be found at www.clinicaltrials.gov (link is external).

About Clostridium difficile

Clostridium difficile (C. difficile) is a spore-forming pathogen that typically causes symptoms in individuals with altered gut microbial flora, releasing toxins that can result in a range of disease manifestations from asymptomatic colonization to diarrhea, pseudomembranous colitis, toxic megacolon, intestinal perforation, or, in the most severe cases, death.4,5 C. difficile, classified by the U.S. Centers for Disease Control and Prevention (CDC) as an urgent public health threat in 2013,6 is the most common cause of antibiotic-associated diarrhea in the healthcare setting and an increasing concern worldwide.7 Responsible for approximately 453,000 U.S. cases (associated with 29,000 deaths) in 2011,8 CDI disproportionately affects older adults, with nearly two-thirds of cases in patients over the age of 65.9 Current treatment options may offer temporary therapeutic improvements, but will not provide long-term protection.10 Up to 25% of patients treated for a first episode of CDI experience a first recurrence of infection, and up to 65% of those patients who experience a first recurrence will experience multiple recurrences.1,11

Pfizer Inc.: Working together for a healthier world™

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of healthcare products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer healthcare products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. For more information, please visit us at www.pfizer.com. In addition, to learn more, follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube, and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release is as of January 26, 2017. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about a vaccine candidate, PF-06425090, including its potential benefits and the expected timing of commencement of a Phase 3 study, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical trial commencement and completion dates and regulatory submission dates, as well as the possibility of unfavorable clinical trial results, including unfavorable new clinical data and additional analyses of existing clinical data; risks associated with interim data; whether and when any biologics license applications may be filed for PF-06425090; whether and when any such applications may be approved by regulatory authorities, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of PF-06425090 and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2015 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results,” as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov (link is external) and www.pfizer.com.

1 Cohen SH et al. Infect Control Hosp Epidemiol. 2010;31:431-455.

2 Gerding DN and Young VB. Clostridium difficile infection. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8th ed. Bennett JE, Dolin R, Blaser MJ (eds). Philadelphia, PA: Elsevier Saunders; 2015.

3 U.S. Food and Drug Administration. Fast Track. http://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm (link is external). Accessed January 2017.

4 Burtis CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th ed. St. Louis, Missouri: Elsevier Saunders; 2012.

5 Savidge TC, Pan W-H, Newman P, et al. Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine. Gastroenterology 2003;125(2):413-20.

6 Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. Washington, DC: Centers for Disease Control and Prevention; 2013.

7 Association for Professionals in Infection Control & Epidemiology. Guide to the elimination of Clostridium difficile in healthcare settings 2008.

8 Lessa FC et al. N Engl J Med. 2015;372:825-834.

9 Bauer MP et al. Lancet. 2011;377:63-73.

10 Ivarsson ME et al. Drug Discov Today. 2015;5:602-608.

11 McFarland LV et al. JAMA .1994;271:1913-1918.

 

Source:

http://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_positive_top_line_results_from_phase_2_study_of_investigational_clostridium_difficile_vaccine_for_the_prevention_of_c_difficile_infection

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

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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]

Synthetic Biologics SYN-004 (ribaxamase) Achieves Primary Endpoint in Phase 2b Trial for C. difficile Infection

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Synthetic Biologics’ SYN-004 (ribaxamase) Achieves Primary Endpoint
in Phase 2b Trial for C. difficile Infection (CDI)

 

Synthetic Biologics, Inc. a late-stage clinical company developing therapeutics
that preserve the microbiome to protect and restore the health of patients, today
announced positive topline data from its Phase 2b clinical trial for SYN-004 (ribaxamase),
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 study, a randomized, double-blind, placebo controlled trial of 412 patients, met its primary endpoint of significantly reducing C. difficile Infection (CDI). Preliminary analysis of the data indicated seven confirmed cases of CDI in the placebo group compared to two cases in the ribaxamase treatment group. Patients receiving ribaxamase achieved a 71.4% relative risk reduction (p-value=0.045) in CDI rates compared to patients receiving placebo. Adverse events reported during this trial were comparable between treatment and placebo arms.

Synthetic Biologics is also in the process of analyzing data from several exploratory endpoints that were designed to evaluate ribaxamase’s ability to protect the gut microbiome from colonization by opportunistic bacteria such as C. difficile and other antibiotic-resistant pathogens. Preliminary analysis of the data demonstrated a significant reduction in new colonization by vancomycin-resistant enterococci (VRE) for patients receiving ribaxamase compared to placebo (p-value=0.0002). With agreement from the FDA, the study included a secondary endpoint to assess ribaxamase’s capacity to decrease the incidence of antibiotic-associated diarrhea from all causes. Preliminary analysis of the data suggested a trend towards such a reduction (p-value=0.13), which was due, for the most part, to the reduction of CDI.

These data are consistent with ribaxamase’s mechanism of action designed to protect and preserve the natural balance of the gut microbiome from the unintended effects of IV antibiotic use. The Company expects to share additional results from these exploratory endpoints as they become available later this year, including results focused on ribaxamase’s ability to prevent the emergence of antimicrobial resistance in the gut microbiome.

“These trial results provide a compelling demonstration of the potential of ribaxamase to help address the serious health impacts associated with CDI and infections from other opportunistic bacteria resulting from dysbiosis of the gut microbiome,” said Joseph Sliman, MD, SVP, Clinical and Regulatory Affairs. “More than 453,0001 patients are diagnosed with CDI annually in the U.S., resulting in approximately 29,0001 deaths as well as significant and sometimes prolonged illness. Ribaxamase has the potential to shorten hospital stays, diminish morbidity and mortality and reduce the emergence of antibiotic-resistant organisms in the gut microbiome by protecting patients from primary C. difficile infection resulting from IV antibiotic use.”

In addition to causing significant suffering and mortality, CDI adds an estimated economic burden of nearly $1.5 billion1 to the healthcare system each year, which could potentially be reduced with an effective therapeutic.

“The reduction in the relative risk of CDI represents a significant milestone in the clinical development of ribaxamase and we believe provides further validation for our approach to advancing cutting edge microbiome science,” said Jeffrey Riley, President and Chief Executive Officer. “These findings also help further our goals to bring the first ever microbiome-focused therapeutic to patients and to help illuminate the potential of this drug class to address serious diseases and public health concerns. We expect to share additional data from exploratory endpoints in the coming months and look forward to continuing ongoing and productive discussions with both the FDA and CDC on the protocol for Phase 3 pivotal trials for ribaxamase.”

Synthetic Biologics is also continuing to prepare for the initiation of pivotal Phase 2b/3 clinical trials for SYN-010, the Company’s proprietary, modified-release formulation of lovastatin lactone designed to treat the underlying cause of irritable bowel syndrome with constipation (IBS-C).

Presentation Planned for Biotech Showcase 2017 Conference

Date: Monday, January 9, 2017
Time: 9:30 a.m. (PT) / 12:30 p.m. (ET)
Location: Hilton San Francisco Union Square, San Francisco, CA

A live webcast of Synthetic Biologics’ presentation may be accessed by logging onto the internet at https://event.webcasts.com/viewer/event.jsp?ei=1130367. After the presentation, a replay will be archived and accessible for 90 days at the same website.

About SYN-004 (ribaxamase) and the Phase 2b Study

SYN-004 (ribaxamase) is a first-in-class oral enzyme designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of CDI, AAD and the emergence of antibiotic-resistant organisms. The Phase 2b proof-of-concept clinical trial is intended to evaluate the effectiveness of ribaxamase to prevent the onset of primary C. difficile infection (CDI), antibiotic-associated diarrhea (AAD) and the emergence of antibiotic-resistant organisms in patients hospitalized with a lower respiratory infection and receiving IV ceftriaxone. A total of 412 subjects were randomized in a 1:1 ratio receiving either 150 mg dose strength of SYN-004 (ribaxamase) or placebo orally QID from Day 1 and until 72 hours following their last treatment of IV ceftriaxone. The sample size was determined to provide 80% power to detect the treatment effect with a one-sided alpha of 0.05. P-values were determined based on a 1-sided z-test for the comparison of the treatment difference as pre-specified in the statistical analysis plan. To access the ribaxamase mechanism of action video on Synthetic Biologics’ website, please click here.

About Synthetic Biologics, Inc.

Synthetic Biologics, Inc. (NYSE MKT: SYN) is a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients. The Company’s lead candidates poised for Phase 3 development are: (1) 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), and (2) SYN-004 (ribaxamase) which is designed to protect the gut microbiome from the effects of certain commonly used intravenous (IV) beta-lactam antibiotics for the prevention of C. difficile infection, antibiotic-associated diarrhea (AAD) and the emergence of antibiotic-resistant organisms. The Company is also developing preclinical stage monoclonal antibody therapies for the prevention and treatment of pertussis and novel discovery stage biotherapeutics for the treatment of phenylketonuria (PKU). For more information, please visit Synthetic Biologics’ website at www.syntheticbiologics.com.

This release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, forward-looking statements can be identified by terminology such as “may,” “should,” “potential,” “continue,” “expects,” “anticipates,” “intends,” “plans,” “believes,” “estimates” and similar expressions and include statements regarding the potential of ribaxamase to help address the serious health impacts associated with CDI and infections from other opportunistic bacteria resulting from dysbiosis of the gut microbiome, the industry data regarding the expected incidence and economic burden of CDI, the potential of ribaxamase to shorten hospital stays, diminish morbidity and mortality and reduce the emergence of antibiotic resistant organisms in the gut microbiome by protecting patients from primary C. difficile infection resulting from IV antibiotic use, the potential to reduce the economic burden to the healthcare system from an effective therapeutic, the suggested trend toward a reduction of incidence of antibiotic-associated diarrhea from all causes, the expected timing of data release of exploratory endpoints of the trial focused on the ability of ribaxamase to prevent the emergence of antibiotic-resistant organisms in the gut microbiome, the continued ongoing discussions with the FDA and CDC, validation for our approach to advancing cutting edge microbiome science, the continued preparation  for the initiation of pivotal Phase 2b/3 clinical trials for SYN-010, the potential of the drug class to address serious diseases and public health concerns, the ability of SYN-004 to protect the gut microbiome from the effects of certain commonly used IV beta-lactam antibiotics for the prevention of  C. difficile infection, antibiotic-associated diarrhea (AAD) and the emergence of antibiotic-resistant organisms. These forward-looking statements are based on management’s expectations and assumptions as of the date of this press release and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, Synthetic Biologics’ product candidates demonstrating safety and effectiveness, as well as results that are consistent with prior results, Synthetic Biologics’ ability to initiate clinical trials and if initiated, to complete them on time and achieve desired results and benefits, Synthetic Biologics’ clinical trials continuing enrollment as expected, Synthetic Biologics’ ability to obtain regulatory approvals for commercialization of product candidates or to comply with ongoing regulatory requirements, regulatory limitations relating to Synthetic Biologics’ ability to promote or commercialize its product candidates for specific indications, acceptance of its product candidates in the marketplace and the successful development, marketing or sale of Synthetic Biologics’ products by competitors that render Synthetic Biologics’ products obsolete or non-competitive, Synthetic Biologics’ ability to maintain its license agreements, the continued maintenance and growth of Synthetic Biologics’ patent estate, Synthetic Biologics becoming and remaining profitable, Synthetic Biologics’ ability to establish and maintain collaborations, Synthetic Biologics’ ability to obtain or maintain the capital or grants necessary to fund its research and development activities, a loss of any of Synthetic Biologics’ key scientists or management personnel, and other factors described in Synthetic Biologics’ Annual Report on Form 10-K for the year ended December 31, 2015 and its other filings with the SEC, including subsequent periodic reports on Forms 10-Q and 8-K.The information in this release is provided only as of the date of this release, and Synthetic Biologics undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

1: Leffler DA et al. N Engl J Med 2015; 372: 1539-1548

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/synthetic-biologics-syn-004-ribaxamase-achieves-primary-endpoint-in-phase-2b-trial-for-c-difficile-infection-cdi-300386140.html

SOURCE Synthetic Biologics, Inc.

C. diff. Solution Tablets by 3M™ – EPA Registered To Kill C.diff. Spores In 4 Minutes

On November 21, 2016  3M™  shared a press release introducing the

C.diff. Solution Tablets – EPA Registered to Kill C.diff. Spores in 4 minutes.

Jean Parsons [#Beginning of Shooting Data Section] Image Size:L (7360 x 4912), FX 2016/09/20 13:49:04.33 Time Zone and Date:UTC-6, DST:ON Tiff-RGB (8-bit) Nikon D810 Lens:VR 24-70mm f/2.8E Focal Length:70mm Focus Mode:Manual AF-Area Mode:Single VR:ON AF Fine Tune:OFF Aperture:f/22 Shutter Speed:1/160s Exposure Mode:Manual Exposure Comp.:-0.7EV Exposure Tuning: Metering:Matrix ISO Sensitivity:ISO 200 Device: White Balance:Direct sunlight, 0, 0 Color Space:sRGB High ISO NR:ON (Normal) Long Exposure NR:OFF Active D-Lighting:Auto Image Authentication: Vignette Control:Normal Auto Distortion Control:OFF Picture Control:[VI] VIVID Base:[VI] VIVID Quick Adjust:0.00 Sharpening:4.00 Clarity:+1.00 Contrast:0.00 Brightness:0.00 Saturation:0.00 Hue:0.00 Filter Effects: Toning: Optimize Image: Color Mode: Tone Comp.: Hue Adjustment: Saturation: Sharpening: Latitude: Longitude: Altitude: Altitude Reference: Heading: UTC: Map Datum: [#End of Shooting Data Section]

When most people think of hospitals, they imagine a safe, clean environment where patients can comfortably receive treatments in an effort to get healthy. However, in reality, hospitals can pose potential risks to both patients and staff, through the threat of infections caused by pathogens such as MRSA, E. coli and C. difficile (C. diff.).

 

 

Remarkably, C. diff contributes to nearly 29,000 deaths every year – almost matching the number of deaths caused by influenza.[i] Despite the prevalence of this organism, prevention and containment pose numerous challenges as the spores can survive for weeks on a large variety of surfaces.

To combat the rise of C. diff infections at hospital facilities, 3M recently launched 3M™ C. diff Solution Tablets, providing a proven, effective alternative to bleach and peracetic acid disinfectants.

Now available for use in the U.S., the new product delivers on effectiveness, efficiency and value, by providing the following:

Effectiveness

  • EPA-registered to kill diff spores in four minutes
  • Effective against Norovirus
  • Safer than bleach and peracetic acid, featuring an NFPA rating of 0,0,0 with no personal protective equipment required at use dilution
  • In-use pH of 5.5 to 6.5, which is closer to neutral than bleach or peracetic acid

Efficiency

  • Dissolves in approximately three minutes with a mild chlorine smell
  • Tablets are available in two sizes for use in large and small containers
  • The product can be applied with a cloth, wipe, mop, or coarse trigger sprayer, and will not bind to common wiping media

Value

  • Costs significantly less than ready-to-use bleach
  • Yields a three-year shelf life in sealed packets, and seven-day shelf life when diluted and stored in a closed container

 

“We are excited to provide our customers with an effective solution for the battle against C. diff,” said Adrian Cook, product marketer for chemicals at 3M Commercial Solutions Division. “The reduction and prevention of infections is an important focus for our customers and we look forward to continuing our work in ensuring safe environments.”

In addition to the new product launch, 3M Commercial Solutions Division also announced the expansion of its Flow Control System product line through the introduction of four additional chemical offerings:

 

  • 3M™ Quat Disinfectant Cleaner Concentrate 5A
    EPA-registered disinfectant cleaner for use in hospitals. Kills HIV-1, MRSA, VRE, herpes simplex I and II and other pathogens. Rinse-free, pleasant fragrance. 0.5 gallon concentrate bottle yields 107 ready-to-use gallons. 4/case.

 

  • 3M™ Neutral Quat Disinfectant Cleaner Concentrate 23A
    EPA-registered disinfectant cleaner kills HIV-1, MRSA, VRE, herpes simplex I and II, and other pathogens. Rinse-free, low foaming, neutral pH formula. 0.5 gallon concentrate bottle yields 100 ready-to-use gallons. 4/case.

 

  • Scotchgard™ Pretreatment Cleaner Concentrate 28A
    Hard-working cleaner for heavily soiled areas of colorfast carpet. Use as a pre-spray prior to extraction or shampooing to loosen soils and stains. 0.5 gallon concentrate bottle yields 26 ready-to-use gallons. 4/case.

 

  • 3M™ Bathroom Cleaner Concentrate 44A
    Green Seal™ Certified bathroom cleaner. Removes soap scum and scale from bathroom surfaces. 0.5 gallon concentrate bottle yields 28 ready-to-use gallons. 4/case.

For more information about 3M™ C. diff Solution Tablets and the 3M Flow Control System, please visit www.3M.com/facility

###

3M Company.

All other trademarks listed herein are owned by their respective companies.

Source:  3M Company

 

*PLEASE NOTE – The C Diff Foundation does not endorse any products and/or clinical study in progress. All website postings are strictly for informational purposes only. Thank  you.

Infection Prevention – Patient Safety – Prior And During A Hospital Stay

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This is a patient – safety article and quite informative and beneficial for everyone.  The topics are highlighted on how to prevent infections prior and during a hospital stay.

 

The most pertinent information to review and share with others is as follows:

1. Check Up on Your Hospital
See how it compares with others on central line, C. diff, and MRSA infections, as well as other measures of patient safety. To compare hospitals in your area at preventing infections, use our hospital ratings.

2. Have a Friend or Family Member With You
That person can act as your advocate, ask questions, and keep notes. A Consumer Reports survey of 1,200 recently hospitalized people found that those who had a companion were 16 percent more likely to say that they had been treated respectfully by medical personnel. The most important times to have a companion for preventing infections and other medical errors are on nights, weekends, and holidays, when staff is reduced, and when shifts change.

3. Keep a Record
Keep a pad and pen nearby so that you can note what doctors and nurses say, which drugs you get, and questions you have. If you spot something worrisome, such as a drug you don’t recognize, take a note or snap a picture on your phone. You can also use your phone to record thoughts or conversations with staff. Though some may object, “explain that you are recording so you remember later,” McGiffert says.

4. Insist on Clean Hands
Ask everyone who enters your room whether they’ve washed their hands with soap and water. Alcohol-based hand sanitizer is not enough to destroy certain bacteria, such as the dangerous C. diff. Don’t hesitate to say: “I’m sorry, but I didn’t see you wash your hands. Would you mind doing it again?”

https://cdifffoundation.org/hand-washing-updates/

 

5. Keep It Clean
Bring bleach wipes for bed rails, doorknobs, the phone, and the TV remote, all of which can harbor bacteria. And if your room looks dirty, ask that it be cleaned.

6. Cover Wounds
Some hospitals examine incisions daily for infection, but opening the bandage exposes the area to bacteria. Newer techniques—sealing the surgical site with skin glue (instead of staples, which can harbor bacteria) and waterproof dressings that stay on for one to three weeks without opening—are effective at preventing infection.

7. Inquire Whether IVs and Catheters Are Needed
Ask every day whether central lines, urinary catheters, or other tubes can be removed. The longer they’re left in place, the greater the infection risk.

8. Ask About Antibiotics
For many surgeries, you should get an antibiotic 60 minutes before the operation. But research suggests that the type of antibiotic used or the timing of when it’s administered is wrong in up to half of cases.

Listen to one of the educational Podcasts:  Using antibiotics wisely, How to help in the fight against antibiotic resistance  with Guests Dr. Arjun Srinivassan, MD and Dr. Lauri Hicks, DO

https://www.voiceamerica.com/episode/93656/encore-using-antibiotics-wisely-how-you-can-help-in-the-fight-against-antibiotic-resistance

9. Postpone Surgery If You Have an Infection
That increases your risk of developing a new infection and worsening an existing one. So if you have any other type of infection—say, an abscessed tooth—then the surgery should be postponed, if possible, until it’s completely resolved.

10. Say No to Razors
Removing hair from the surgical site is often necessary, but doing that with a regular razor can cause nicks that provide an opening for bacteria. The nurse should use an electric trimmer instead.

11. Question the Need for Heartburn Drugs
Some patients enter the hospital taking heartburn drugs such as Nexium, lansoprazole (Prevacid) or omeprazole (Prilosec) or are prescribed one after they’re admitted. But these drugs, called proton-pump inhibitors, increase the risk of intestinal infections and pneumonia, so consider stopping them before admission and, once there, ask whether you really need one.

12. Test for MRSA
Ask your surgeon to screen you for MRSA, a potentially deadly bacteria that’s resistant to antibiotics, either before you enter or on admission, so that you can address the problem and hospital staff can take extra steps to protect you and others.

13. Watch for Diarrhea
Get tested for C. diff. infection  if you have three loose stools within 24 hours. If you test positive, expect extra precautions for preventing infections from spreading to others.

14. Quit Smoking, Even Temporarily
You won’t be allowed to smoke in the hospital anyway, and stopping as long as possible beforehand cuts the risk of infection. Read our advice on how to stop smoking.

15. Wash Up the Night Before Surgery
Ask about taking precautions before entering the hospital, such as bathing with special soap or using antiseptic wipes.

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

C. diff. Awareness Across the Globe

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Beginning November 1st,

join the C Diff Foundation in

“Raising C. diff.  Awareness.”

Let’s begin with promoting C. difficile prevention to share in witnessing a decrease in C. difficile infections worldwide.

Ways to PREVENT acquiring a C. diff. infection:

HAND-WASHING remains the #1 course of action in infection prevention.

Knowing how and when to wash hands is also important.

Correct Hand-washing steps to follow:

  • Wet your hands with clean, running water (warm or cold), turn off the tap, and apply soap.
  • Lather your hands by rubbing them together with the soap. Be sure to lather the backs of your hands, between your fingers, and under your nails.
  • Scrub your hands for at least 30 seconds. Need a timer? Hum the “Happy Birthday” song from beginning to end twice.
  • Rinse your hands well with water.
  • Dry your hands using a clean towel.
  • Turn off faucets with a clean dry towel, and wipe hands with a clean dry towel.

WHEN is it a good time to wash hands?

  • Before, during, and after handling and preparing food.
  • Upon Entering a Patient’s room and Before Existing a Patient’s room.
  • Before and after eating.
  • Before and after patient care.
  • Before and after treating a cut or wound.
  • Before  exiting a restroom.
  • After changing diapers.
  • After blowing your nose, coughing, or sneezing.
  • After petting a pet or any livestock animals.
  • After touching garbage.
  • AND OFTEN.

Limit Antibiotic Use — Discuss Symptoms With Healthcare Providers.

The Centers of Disease Control and Prevention recommends infection control protocols be shared between healthcare professionals and long-term facility administrators for the safety of the patient, visitors, and other patient’s safety.

Question the necessity of antibiotics to treat symptoms.  Unnecessary use of antibiotics raises the risk of acquiring a C. difficile infection.  Remember antibiotics do not effect viruses.  Healthcare professionals; confirming a bacterial infection before prescribing antibiotic course of treatment is advised.

Take the Antibiotic “Resistance Fighter” Pledge

How to be a resistance fighter:  Limit the use of Antibiotics! Understand that antibiotics are only effective against bacteria and not viruses: colds, flu and most coughs are caused by viruses and will get better on their own.  Treat your flu and cold symptoms and let your immune system fight the virus.  Antibiotics will not help you get better quickly, and may give you side effects such as diarrhea and thrush. They can also lead to acquired C. diff. infections. They won’t stop your virus spreading to other people only YOU can do that with good hand hygiene.  Don’t ask for antibiotics , instead ask your doctor about the best way to treat your symptoms.   If you are prescribed antibiotics ask your doctor about the risks and benefits and always take them exactly as prescribed. Never take someone else’s antibiotics, always speak with your Primary Care Physician (PCP) or healthcare professional when symptoms linger or worsen.

Let us all take the “Resistance Fighter” Pledge and feel free to share the pledge with            everyone you know

I will not expect antibiotics for colds and flu as they have no effect on viruses.
I will take antibiotics as directed IF I am prescribed them, and not ask for them.
I will practice good hygiene, making hand washing #1, and help stop giving germs a free ride.

Now we can ALL spread knowledge, not infections and encourage others to join the fight against antibiotic resistance.

“Get Smart: Know When Antibiotics Work” CDC Campaign :

Get Smart About Antibiotics Week has been an annual effort to coordinate the work of CDC’s Get Smart: Know When Antibiotics Work campaign, state-based appropriate antibiotic use campaigns, non-profit partners, and for-profit partners during a one week observance of antibiotic resistance and the importance of appropriate antibiotic use. The campaign organized its first annual Get Smart About Antibiotics Week in 2008. CDC’s Get Smart campaign, housed in the National Center for Immunization and Respiratory Diseases, collaborated with state-based appropriate antibiotic use campaigns and non-profit and for-profit partners. The success of the pilot year was measured by 1) dissemination of educational materials and messages, 2) partner satisfaction, and 3) media interest. A robust evaluation of the pilot week determined that each of these goals was met and exceeded. This was followed by other successful Get Smart About Antibiotics Week observances.

During November 14-20th, 2016 —  the Annual Get Smart About Antibiotics Week will be observed. As in past years, the effort will coordinate work of CDC’s Get Smart: Know When Antibiotics Work campaign, state-based appropriate antibiotic use campaigns, non-profit partners, and for-profit partners during a one week observance of antibiotic resistance and the importance of appropriate antibiotic use. As with the past observances, messages and resources for improving antibiotic use in  healthcare settings from CDC’s Get Smart for Healthcare campaign will be included. Get Smart for Healthcare is a program housed in CDC’s National Center for Emerging and Zoonotic Infectious Diseases.

  • Ask your physician questions such as, “Do I really need an antibiotic?”
  • Bacteria only, not viruses (common cold, flu), can be killed by antibiotics.
  • Complete the entire course of prescribed antibiotics, even if you feel better midway through.

Antibiotic resistance occurs when bacterial changes reduce or eliminate an antibiotic’s ability to kill the bacteria.

The Association of Professionals in Infection Control and Epidemiology (APIC)  recommends the following:

  • Take antibiotics only and exactly as instructed by your healthcare provider.
  • Only take antibiotics prescribed for you.
  • Do not save or share antibiotics prescribed to you.
  • Do not pressure your healthcare provider to prescribe you antibiotics.

C. diff. Testing:  When a patient presents symptoms (diarrhea with abdominal cramping/pain, fatigue, fever) ordering a C. difficile stool test to rule out a C. diff. infection is beneficial, especially if the patient has been treated with antibiotics within ninety-days.

Environmental Safety:  Disinfecting a patient’s room, treated for a positive C. difficile infection, with a bleach or Federal EPA registered spore-killing product will help eliminate      C. difficile spores from being spread to another patient’s room.  Environmental safety is also an important matter in home-care.  Cleaning all high-touch areas in both long-term and acute care facilities, and home environments will help decrease the spread of this infection.  (High-touch surfaces: light switches, door knobs/handles, bed-side commodes, bathroom hand rails, commode, sink and sink handles, counter-tops, floors, bath-tubs, showers, canes, wheel-chairs, and all medical equipment in a patient’s room).

Personal Protection: ISOLATION: Visitors and Environmental professionals, wear proper personal protection equipment when treating and cleaning areas/rooms of a     C. difficile patient.  (gloves, gowns, shoe coverings, protective eye wear if using using spray solutions).

Patient Isolation:  Contact Precautions: Protect the patient and others by keeping a C. difficile patient in isolation in long-term and acute care facilities.  This will prevent the spread of infection to others and other areas within the facilities.

Communication:  If a patient is being transferred from either a long-term or acute care facility, communicate to the facility intake personnel the patient’s C. diff. infection and necessary infection control protocols to be implemented for the patient and other patient’s safety.

The CDC has been sharing public announcements regarding the use of Antibiotics for both healthcare professionals and patients alike.  Colds, Ear and Sinus symptoms may be caused by a virus, not bacteria.  Taking antibiotics to treat a virus makes antibiotic medications less effective when they are needed while raising the risk of acquiring a C. difficile infection.  Limit the use of Antibiotics to reduce the risk of acquiring a C. difficile infection  (Bacterial infections and the treatment of symptoms will be determined and should be followed by the treating healthcare professionals). * November 17-23rd, 2014 join the CDC’s Get Smart: Know When Antibiotics Work campaign.

“None of us can do this alone…..all of us can do this together”

For additional C. difficile information, review the Infection Prevention categories available on the website :   http://www.cdifffoundation.org

 

 

 

Sources: CDC