Category Archives: C. diff. prevention

C. diff. Infections Related to Dental Care and the Unnecessary Use of Antibiotics

During the annual ID Week2017— an annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS)— researchers presented findings that suggest that the prevalence of Clostridium difficile is likely caused by the unnecessary prescription of antibiotics by dentists.

“Dentists have been overlooked as a source of antibiotic prescribing, which can potentially delay treatment when doctors are trying to determine what is causing a patient’s illness,” Stacy Holzbauer, DVM, MPH, lead author of the study and career epidemiology field officer for the CDC and MDH, said in a statement. “It’s important to educate dentists about the potential complications of antibiotic prescribing, including C. diff.

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

https://www.rdmag.com/article/2017/10/dentists-overprescribing-antibiotics-overlooked-cause-superbug-infection

“Dentists write more than 24.5 million prescriptions for antibiotics a year,” she added. “It is essential that they be included in efforts to improve antibiotic prescribing.”

C. diff is a deadly bacterial infection that causes severe and possibly fatal diarrhea. Taking antibiotics can put patients at an increased risk for developing the infection.

“Research has shown that reducing outpatient antibiotic prescribing by 10 percent could decrease C. diff rates outside of hospitals by 17 percent,” Holzbauer said. “Limiting the use of inappropriate antibiotics in dentistry could also have a profound impact.”

For the study, the Minnesota Department of Health tracked community-associated C. diff infections—patients who did not have an overnight stay in a hospital or nursing home—in five Minnesota counties.

For the study, the researchers interviewed 1,626 people with community-associated C. diff between 2009 and 2015, 57 percent of which reported they had been prescribed antibiotics.  The researchers also found that patients that were prescribed antibiotics for tended procedures tended to be older and likely received the medication ….   clindamycin.

The six-year study shows that 15 percent of those with the infection had taken antibiotics prescribed to them from dental procedures, one-third of which had a medical chart that did not list dental procedure-related antibiotics, highlighting the apparent disconnect between dental care and medical care.

Another study conducted by the MDH found that 36 percent of dentists prescribed antibiotics in situations that were generally not recommended by the American Dental Association.

“It is possible some dentists aren’t aware of the updated recommendations or are being asked by other healthcare providers to continue preventive antibiotics despite the change,” Holzbauer said.

Hand-Washing aka Hand Hygiene Patient Education Proves Successful To Reduce C.diff. Infections

HandHygiene #1 Prevention

Hand-Washing aka hand hygiene Remains #1 In Infection Prevention In Every Setting.

“Despite evidence to suggest that [hand hygiene] is important in preventing infection, hospitalized patients are often not provided the opportunity to clean their hands,” due to mobility and cognitive obstacles as well as lack of education, investigators wrote.

Education on patient hand hygiene significantly reduced the incidence of Clostridium difficile infection at University of Pittsburgh Medical Center Mercy Hospital.

First, they conducted baseline surveys to assess patient hand hygiene, which showed patients needed more opportunities to wash their hands. Then nurse educators provided staff with an educational presentation on the importance of patient hand hygiene for preventing infection, which included specific times they should encourage and assist patients with hand hygiene. Staff then provided education and assistance to newly admitted patients, and researchers conducted additional surveys after implementation of this intervention.

During the first phase of the study involving just four medical-surgical nursing units, patient hand hygiene education increased significantly after the intervention (P < .0001). Overall, 97 follow-up surveys showed the proportion of those who received hand hygiene education increased from 34% to 64%, the opportunities provided for hand hygiene increased from 60% to 86%, and the average number of times hand hygiene was performed daily increased from 2.7 to 3.75.

After expanding the intervention to the whole hospital in the second phase of the study, 189 follow-up surveys showed that patient hand hygiene education increased from 48% to 53%. Meanwhile, overall opportunities for hand hygiene remained unchanged from 68%, and daily frequency of patient hand hygiene did not change significantly (mean, 2.4 vs. 2.6 times per day).

Notably, CDI rates dropped significantly during the 6 months following hospital-wide implementation.

“[Standardized infection ratio] P values for Q2 and W3 (0.0157 and 0.0103, respectively) were significantly lower than expected (P .05),” investigators wrote. “The Q4 SIR, however, showed an increase to 0.3844 over the 2 preceding quarters.”

They concluded that these findings showed patient hand hygiene “should be considered a potential addition to CDI prevention measures in hospitalized patients.” – by Adam Leitenberger

Source:  https://www.healio.com/gastroenterology/infection/news/online/%7B0ea95c50-ddec-4259-a229-5979fde9d8af%7D/patient-handwashing-cuts-c-difficile-rate-in-hospital

Study Show 9% Fewer Antibiotics Prescribed

The use of antibiotics among Americans with commercial health insurance has decreased during the past several years, according to a new analysis that nevertheless
shows lingering variations for different ages and in different parts of the country.

The study released provides the latest evidence of how doctors and patients have begun to heed warnings that excessive antibiotic use breeds dangerous drug resistance and “superbug” bacteria.

The analysis is based on 173 million insurance claims from people under age 65 with Blue Cross Blue Shield coverage
who filled prescriptions
between 2010 and 2016.

 

It is a sequel of sorts to research by the federal Centers for Disease Control and Prevention, which found a smaller decline and comparable age and geographic variations.

The CDC reported a 5 percent decrease overall between 2011 and 2014 in antibiotic prescriptions written in outpatient settings such as doctors’ offices, clinics and hospital emergency rooms.

The study by the Blue Cross Blue Shield Association found that 9 percent fewer antibiotics prescribed in outpatient settings were filled in 2016, compared with 2010.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The Blue Cross Blue Shield Study:

https://www.bcbs.com/the-health-of-america/reports/antibiotic-prescription-rates-declining-in-the-US?utm_source=social&utm_medium=linkedin&utm_content=&utm_campaign=hoa-antibiotics

 

To read more of this article please click on the link provided below:

https://www.washingtonpost.com/news/to-your-health/wp/2017/08/24/fewer-antibiotic-prescriptions-are-being-filled-a-new-analysis-finds/?utm_term=.d30b61b8fae7

Changing the Bed Linens In Sickness and In Health

According to Microbiologist, Phillip Tierno of New York University

our bed linens can “quickly blossom into a botanical park of bacteria and fungus.”

If left for too long, the microscopic life within the wrinkles and folds of our bed sheets can even make us sick,

> We can recall – years ago – the bed linens in any acute care facility (e.g., hospital) the bed linens were changed daily.   Food for thought <<

 

Humans naturally produce roughly 26 gallons of sweat in bed every year. When it’s hot and humid outside, this moisture becomes what scientists call an “ideal fungal culture medium.”

In a recent study that assessed the level of fungal contamination in bedding, researchers found that a test sample of feather and synthetic pillows that were 1 1/2 to 20 years old contained as many as 16 species of fungus each.

And it’s not just your own microbial life you’re sleeping with. In addition to the fungi and bacteria that come from your sweat, sputum, skin cells, and vaginal and anal excretions, you also share your bed with foreign microbes.

These include animal dander, pollen, soil, lint, dust mite debris and feces, and finishing agents from whatever your sheets are made from, to name a few.

Tierno says all that gunk becomes “significant” in as little as a week. And unclean bedding still exposes you to materials that can trigger the sniffing and sneezing, since the microbes are so close to your mouth and nose that you’re almost forced to breathe them in.

“Even if you don’t have allergies per se, you can have an allergic response,” Tierno said.

Another reason your sheets get dirty quickly has little to do with your behavior or sweat patterns — the issue is simply gravity.

“Just like Rome over time was buried with the debris that falls from gravity, gravity is what brings all that material into your mattress,” Tierno said.

One to two weeks of this buildup is enough to leave anyone with a scratchy throat — especially those with significant allergies or asthma. (One in six Americans has allergies.)

“If you touched dog poo in the street, you’d want to wash your hands,” Tierno said.

“Consider that analogous to your bedding. If you saw what was there — but of course you don’t see it — after a while you have to say to yourself, ‘Do I want to sleep in that?’

So what does Dr. Tierno suggest?

To stem the invisible tide, he said, sheets should be washed once a week — >> More Often when bed linens are visibly soiled and an infection is being treated <<


Proper ways to handle soiled linens:

There is now a common understanding that linens, once in use, are usually contaminated and could be harboring microorganisms such as MRSA and VRE.

Further, the Centers for Disease Control and Prevention (CDC) cautions that healthcare professionals should “handle contaminated textiles and fabrics with a minimum agitation to avoid contamination of air, surfaces, and persons.” Even one of the leading nursing textbooks, Fundamentals of Nursing, states, “Soiled linen is never shaken in the air because shaking can disseminate secretions and excretions and the micro organisms they contain.” This text also states, “…linens that have been soiled with excretions and secretions harbor microorganisms … can be transmitted to others.”

According to Fundamentals of Nursing, when handling linens in any acute care and healthcare facility:

1. You should always wash your hands after handling a patient’s bed linens.

2. You should hold soiled linen away from your uniform.

3. Soiled linen is never shaken in the air because shaking can disseminate the micro-organisms they contain.

4. Linen from one patient’s bed is never (even momentarily) placed on another patient’s bed.

5. Soiled linens should be placed directly into a portable linen hamper or tucked into a pillowcase and the end of the bed before it is gathered up for disposal in the linen hamper or linen chute.

 

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

http://www.businessinsider.com/how-often-to-wash-bed-sheets-2017-6

 

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

pfizer_logo

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

newsspeaker

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]