Category Archives: C. diff. Research Community

Two UK Researchers, Prof.Alistair Leanord and Dr. David Enoch, Present CDI Data At the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)

Repeated infection with the bacterium Clostridium difficile (C. difficile, C.diff.), which causes abdominal pain, fever, diarrhea is linked to higher death rates, as well as having a significant impact on health services in terms of cost and hospital beds occupied.

In the first of two presentations at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) (tomorrow (Saturday), Professor Alistair Leanord, from Glasgow University, UK, will say that in Scotland the extra impact on the health service from C. difficile infections amounted to 10,600 bed days a year. “This is the equivalent to a 30-bed hospital ward being fully occupied all year,” he will say.

He will tell the congress that the (median) average cost of a patient with C. difficile infection was £7,500 (€8,600 approximately) compared to £2,800 (€3,200 approx) for patients with other medical conditions. In Scotland over a one year period, from October 2015 to October 2016, there were 1,150 cases of C. difficile infection in patients aged 15 and over. This cost the National Health Service (NHS) in Scotland a total of £8,650,000. Out of this amount, the additional costs of treating C. difficile infection, over and above the basic cost of a hospital bed and normal medical care, was £1,955,000. The calculations were carried out at Strathclyde University, which is part of the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI) research consortium.

Until now, little has been known about the impact on health service resources from C. difficile infections, and on patients in terms of recurrence of infection, readmission to hospital, length of stay and death rates.

Prof. Leanord and his colleagues in Scotland identified 3,304 patients with C. difficile in Scottish hospitals between 2010 and 2013 and matched them with 9,516 patients who did not have the infection (the control group). Approximately two-thirds of the C. difficile patients acquired the infection in hospital.

They found that patients with C. difficile infection had more than double the risk of dying from any cause within two months of being admitted to hospital; nearly a third of all C. difficile cases (29%) died within two months compared to 14% of patients in the control group. Patients with C. difficile stayed in hospital a (median) average 9.7 days longer than the patients without the infection. Of the 1,712 C. difficile patients who were discharged from hospital within 30 days of the first episode of infection, 59% were readmitted within six months; of the 626 cases discharged more than 30 days after the first episode 53% were readmitted within six months. Few of these re-admissions were directly related to C. difficile infection.

“However, nearly a sixth of patients (14%) who were cured of the initial infection recurred within three months, and nearly one third of them (29%) had a second recurrence within a year,” says Prof. Leanord.

Older people were more vulnerable to a recurrence. Among the patients with C. difficile infection, 22% were aged 85 or over, and patients aged 75 and over had approximately double the risk of a recurrence of the infection compared to those aged under 65. Patients aged between 65-74 had 1.5 times the risk of recurrence compared to younger patients.

Prof. Leanord will conclude: “Having a clear understanding of the nature of C. difficile infections in Scotland will allow the Scottish government to target resources at the most appropriate patients to try to reduce the overall burden of the disease on the health service. Our findings are very likely to be applicable to the rest of the UK and other countries as well.”

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In a second presentation on Saturday, Dr David Enoch, a consultant microbiologist and infection control doctor at the National Infection Service, Public Health England, Cambridge (UK), will report the outcomes of 6,874 patients who had acquired C. difficile infection in hospital between 2002 and 2013 in England. Of these, 1,141 (16.6%) had recurrences of the infection.

“We found that 49% of hospital patients who suffer a recurrent episode of C. difficile infection die within a year, compared to 38% of those who suffer an initial infection only,” he will say. “In addition, 21% of patients with a recurrence suffered other complications as well, such as dehydration, malnourished and sometimes even perforation of the bowel, compared to 18% of patients who did not have a recurrence.”

Dr Enoch estimates that there are approximately 125,000 cases of C. difficile infection in Europe each year, and between 15-30% of these recur. “Cases in the UK have been coming down since 2008, which is most probably due to improvements in antibiotic prescribing and cleaning regimens in hospitals. This is encouraging but more still needs to be done.”

The average age of the patients was 77 and the average length of stay in hospital was 38 days.

“The main risk factor for developing C. difficile infection is prior antibiotic use. These patients are often already ill from some other underlying illness, which explains why they needed antibiotics in the first place. Older people are at greater risk of C. difficile infection as they are often sicker, have other illnesses or conditions, and so need more antibiotics,” he will say.

Dr Enoch continues: “Although much has been done, particularly in the UK, to try to prevent C. difficile infection, strict adherence to antibiotic guidelines by clinicians and thorough cleaning of the hospital environment are crucial in ensuring that patients don’t develop C. difficile infection in the first place. Treatment with a new drug called fidaxomicin has also been shown to reduce the risk of recurrence in patients who are unfortunate enough to develop an infection. However, we still have a lot to learn, particularly about how C. difficile infection occurs in the community, and how best to treat it.”

Treatments for recurrences of C. difficile infection  —–  include stopping the antibiotic that made the patient susceptible to the infection and starting a different antibiotic that is effective against C. difficile infection. These antibiotics include metronidazole, vancomycin and fidaxomicin. Supportive therapy, such as extra fluids, and surgery in serious or life-threatening cases may also be necessary. Faecal transplantation is emerging as a promising option; this is a process in which the good bacteria that the gut needs but which has been killed off by antibiotics is transplanted into the patient from a healthy donor.

(CDF:  Consider contacting an organization conducting Clinical Trials to Treat and Prevent.  Click on the following link for more information :  https://cdifffoundation.org/clinical-trials-2/

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Abstract no: #1672, presented by Prof. Alistair Leanord in the “Clostridium difficile infections: epidemiology and outcome” oral session, 16.30-18.30 hrs, Saturday 22 April, Hall A.

Abstract no: #883, presented by Dr Enoch in the “Clostridium difficile: guts and glory” e-poster mini-oral session, 15.30-16.30 hrs, Saturday 22 April, ePoster Arena 4.

 

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

https://www.eurekalert.org/pub_releases/2017-04/esoc-cdi041917.php

Clostridium difficile Infection More Prevalent In Patients Undergoing Allogeneic Stem Cell Transplantation

Clostridium difficile infection was more prevalent in patients undergoing allogeneic stem cell transplantation compared with patients undergoing autologous stem cell transplantation, according to findings published in Infection Control & Hospital Epidemiology.

 

C. difficile infection is the most common cause of infectious diarrhea in hospitalized patients,” Nishi N. Shah, MD, MPH, resident at the University of Arkansas for Medical Sciences, Little Rock, Arkansas and colleagues wrote. “Epidemiological studies evaluating the incidence of and morbidity and mortality due to C. difficile infection in hematopoietic stem cell transplant recipients are limited.”

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

http://www.healio.com/infectious-disease/nosocomial-infections/news/in-the-journals/%7B889c4781-fda5-43e5-84ce-629cf3692f57%7D/cdi-more-prevalent-in-allogeneic-stem-cell-recipients

The researchers reviewed patient data from the NIS database, analyzing records on adults admitted for allogeneic stem cell transplantation (n = 33,189) and autologous stem cell transplantation (n = 53,072) between January 2001, and December 2010.

Most patients had received autologous stem cell transplantation (61.5%). Of patients in the allogeneic group, 8.5% had C. difficile infection, compared with 5.8% in the autologous group, the researchers reported. Shah and colleagues wrote that univariate analyses identified a number of risk factors for C. difficile infection, including: age, gender, indication for stem cell transplantation, radiation as part of the conditioning regimen, respiratory failure, septicemia and lengthy hospital stay.

Multivariate analyses for autologous transplantation showed significant correlation between age and indication for transplant, but this indication was not associated with C. difficile infection in either group upon multivariate analysis.

Through multivariate analysis, the researchers found multiple factors associated with C. difficile infection: septicemia (autologous OR = 1.64; 95% CI, 1.35-2; allogeneic OR = 1.69; 95% CI, 1.36-2.1), male gender (autologous OR = 1.29; 95% CI, 1.09-1.53; allogeneic OR = 1.36; 95% CI, 1.18-1.57), lengthy hospital stay (autologous OR = 2.81; 95% CI, 2.29-3.45; allogeneic OR = 2.63; 95% CI, 2.15-3.22) and presence of multiple comorbidities (autologous OR = 1.32; 95% CI, 1.11-1.57; allogeneic OR = 1.18; 95% CI, 1-1.4).

“The current study helps identify higher risk groups for such clinical interventions. Among allogeneic stem cell transplantation recipients, interventions to reduce or treat gut GVHD could also impact C. difficile infection rates,” the researchers wrote. “Many topics of study remain to be explored in the prevention of C. difficile infection among stem cell transplantation patients. Certainly, further interventions to improve outcomes, such as reducing the rate of C. difficile infection, are needed.” – by Andy Polhamus

Rebiotix Reports Topline Results From a Controlled Open-label Phase 2 Trial of RBX2660 (PUNCH™ Open Label) For the Prevention of Recurrent Clostridium difficile (C. diff.) Infection (rCDI)

In The News

April 2017

 

 

Rebiotix Inc., a clinical-stage microbiome company focused on harnessing the power of the human microbiome to treat challenging diseases, today announced topline results from a controlled open-label Phase 2 trial of RBX2660 (PUNCH™ Open Label) for the prevention of recurrent Clostridium difficile (C. diff.) infection.

Data indicated that RBX2660 was well-tolerated and achieved the primary efficacy endpoint of preventing C. diff. recurrence; patients treated with RBX2660 exhibited a treatment success rate of 78.8% compared with a historical control of 51.8% (p<0.0001). RBX2660 is a broad-spectrum microbiota suspension that is designed to rehabilitate the human microbiome by delivering live microbes into a patient’s intestinal tract to treat disease.

Lee Jones, president and CEO of Rebiotix, stated, “The 78.8% treatment success achieved in this open label Phase 2 trial demonstrates the potential of RBX2660, a broad spectrum microbiota drug product, to rehabilitate the gut microbiome and break the cycle of C. diff. recurrence. These results, coupled with the safety and efficacy data observed in our prior Phase 2b and Phase 2 clinical trials, position Rebiotix to advance RBX2660 into Phase 3 clinical development, solidifying our standing as the most clinically advanced microbiome company in the industry.”

PUNCH™ Open Label was designed as a prospective, multicenter, open-label, controlled Phase 2 study to assess the efficacy and safety of RBX2660 for the prevention of recurrent C. diff.

The primary efficacy endpoint involved a comparison of patients treated with RBX2660 to a closely matched set of antibiotic only treated historical controls through 56 days. There were 31 active treatment sites and four control sites in the US and Canada. 132 RBX2660 and 110 historical control subjects were included in this topline analysis.

Actively treated patients, after determining eligibility, were administered two doses of RBX2660; the first at day one and the second at day seven. Patients were then monitored for eight weeks to determine whether there was a recurrence of C. diff.

Top line results from the trial, which examined responses from 132 patients versus a historical control of 110 patients, indicated a treatment success rate of 78.8% as compared to a historical control of 51.8% (p<0.0001). Overall, RBX2660 was generally well-tolerated with the most commonly reported adverse events being gastrointestinal, including diarrhea, abdominal pain, flatulence, constipation and distension.


About Rebiotix Inc.

Rebiotix Inc. is a clinical-stage microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of challenging diseases. Rebiotix is the most clinically advanced microbiome company in the industry, with its lead drug candidate, RBX2660, expected to enter Phase 3 clinical development for the prevention of recurrent Clostridium difficile (C. diff.) infection. Previously, RBX2660 was the subject of three Phase 2 trials in recurrent C. diff, including a Phase 2b randomized, double-blind, placebo-controlled trial (PUNCH™ CD2), with data indicating the drug was well-tolerated and demonstrated statistically significant treatment efficacy. RBX2660 has been granted Orphan Drug status, Fast Track status and Breakthrough Therapy Designation from the FDA for its potential to prevent recurrent C. diff. infection.

Rebiotix’s development pipeline includes multiple formulations targeting several disease indications and is built around its pioneering Microbiota Restoration Therapy (MRT) platform. MRT is a standardized, stabilized drug technology that is designed to rehabilitate the human microbiome by delivering a broad spectrum of live microbes into a patient’s intestinal tract via a ready-to-use and easy-to-administer format.

For More Information About C. difficile Clinical Trials In Progress : 

https://cdifffoundation.org/clinical-trials-2/

 

For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit www.rebiotix.com

 

Source:  Rebiotix 4/17

Researchers Suggest a Portion Of C. diff. Cases In Europe Involve Infections Associated With Other Sources Outside of Healthcare-Associated Infections

As part of a multicenter study, investigators from the University of Oxford, the University of Leeds, Astellas Pharma Europe, and elsewhere used a combination of ribotyping, sequencing, phylogenetics, and geographic analyses to retrace the genetic diversity and potential sources of C. difficile isolates involved in infections in European hospitals.

Recent research suggests a proportion of Clostridium difficile cases in Europe involve not only hospital-acquired infections but also infections associated with other sources, such as food.

As stated in the article:

https://www.genomeweb.com/sequencing/clostridium-difficile-genetic-patterns-europe-point-possible-infection-sources-beyond?utm_source=Sailthru&utm_medium=email&utm_campaign=GWDN%20Mon%20PM%202017-04-24&utm_term=GW%20Daily%20News%20Bulletin

David Eyre, a clinical lecturer at the University of Oxford, was slated to present the work at the European Congress of Clinical Microbiology and Infectious Diseases annual 2017 meeting in Vienna this past weekend. The study was funded by Astellas Pharma’s Europe, Middle East, and Africa (EMEA) program.

“We don’t know much about how C. difficile might be spread in the food chain, but this research suggests it may be very widespread,” Eyre said in a statement. “If that turns out to be the case, then we need to focus on some new preventative strategies such as vaccination in humans once this is possible, or we might need to look at our use of animal fertilizers on crops.”

“This study doesn’t give us any definitive answers,” he explained, “but it does suggest other factors [than hospital infections] are at play in the spread of C. difficile and more research is urgently needed to pin them down.”

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Some of the strains clustered by locale, consistent with spread from one individual to the next, for example in a healthcare setting. But more unexpectedly, the team also saw strains smattered across seemingly unconnected sites. And because at least one of those strains had previously been linked to pig farming, the researchers speculated that some infections may have been transmitted through food sources.

 

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

https://www.genomeweb.com/sequencing/clostridium-difficile-genetic-patterns-europe-point-possible-infection-sources-beyond?utm_source=Sailthru&utm_medium=email&utm_campaign=GWDN%20Mon%20PM%202017-04-24&utm_term=GW%20Daily%20News%20Bulletin

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.”

Clostridium difficile (C.diff.) a Spore Forming Bacteria

Types of spore forming bacteria.

To provide a background and definition of  each of them the following information is beneficial.

Bacteria are a large group of microscopic, unicellular organisms that exist either independently or as parasites. Some bacteria are capable of forming spores around themselves, which allow the organism to survive in hostile environmental conditions. Bacterial spores are made of a tough outer layer of keratin that is resistant to many chemicals, staining and heat. The spore allows the bacterium to remain dormant for years, protecting it from various traumas, including temperature differences, absence of air, water and nutrients. Spore forming bacteria cause a number of diseases, including botulism, anthrax, tetanus and acute food poisoning. (1)

Bacillus

Bacillus is a specific genus of rod-shaped bacteria that are capable of forming spores. They are sporulating, aerobic and ubiquitous in nature. Bacillus is a fairly large group with many members, including Bacillus cereus, Bacillus clausii and Bacillus halodenitrificans. Bacillus spores, also called endospores, are resistant to harsh chemical and physical conditions. This makes the bacteria able to withstand disinfectants, radiation, desiccation and heat. Bacillus are a common cause of food and medical contamination and are often difficult to eliminate.

Clostridium

Clostridium are rod-shaped, Gram-positive (bacteria that retain a violet or dark blue Gram staining due to excessive amounts of peptidoglycan in their cell walls) bacteria that are capable of producing spores. According to the Health Protecton Agency, the Clostridium genus consists of more than a hundred known species, including harmful pathogens such as Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani and Clostridium sordellii.

Some species of the bacteria are used commercially to produce ethanol (Clostridium thermocellum), acetone (Clostridium acetobutylicum), and to convert fatty acids to yeasts and propanediol (Clostridium diolis).

Background:

Scientists discovered C. diff in 1935, but they didn’t recognize it as the major cause of antibiotic-associated diarrhea until 1978. The rise of C. diff in the 1970s was triggered by the widespread use of the antibiotic clindamycin. Over the next 20 years, broad-spectrum antibiotics in the penicillin and cephalosporin families fueled the C. diff epidemic, and in the early years of this century, fluoroquinolone antibiotics were linked to a new and more dangerous hypervirulent strain of C. diff.

C. diff is classified as an anaerobic bacterium because it thrives in the absence of oxygen. Like its cousins, the Clostridia that cause tetanus, botulism, and gas gangrene, C. diff passes through a life cycle in which the actively dividing form transforms itself into the spore stage. Spores are inert and metabolically inactive, so they don’t cause disease. At the same time, though, spores are very tough and sturdy; they are hard to kill with disinfectants, and they shrug off even the most powerful antibiotics.

Here’s how C. diff causes trouble. Patients with C. diff shed spores into their feces. Without strict precautions, spores are inadvertently transmitted to hands, utensils, and foods, and then swallowed by someone else. The spores come to life in the second person’s GI tract, but in the best of circumstances, the normal bacteria keep C. diff in check and illness does not develop. But if the “good” GI bacteria have been knocked down by antibiotics, C. diff gets the upper hand. As C. diff multiplies and grows, it produces toxins that injure the lining of the colon, producing diarrhea, inflammation, and sometimes worse. Ordinary strains of C. diff produce two toxins, called toxins A and B, but the new, worrisome hypervirulent strains produce up to 16 times more toxin A and 23 times more toxin B. (2)

C. diff is an old bacterium,…..the CDAD epidemic is new ……..What turned a medical curiosity into a major threat? In a word, antibiotics.

Antibiotics are marvelous medications, and they are obviously here to stay. But doctors must use them wisely. That means prescribing an antibiotic only when it’s truly necessary, choosing the simplest, most narrowly focused drug that will do the job, and stopping treatment as soon as the job is done. Patients can help by resisting the temptation to demand an antibiotic for every potential infection.

When it comes to using antibiotics properly, less can be more.

Sporolactobacillus

Sporolactobacillus is a group of anaerobic, rod-shaped, spore forming bacteria that include Sporolactobacillus dextrus, Sporolactobacillus inulinus, Sporolactobacillus laevis, Sporolactobacillus terrae and Sporolactobacillus vineae. Sporolactobacillus are also known as lactic-acid bacteria for they are capable of producing the acid from fructose, sucrose, raffinose, mannose, inulin and sorbitol. Sporolactobacillus are found in the soil and often in chicken feed. According to “Fundamentals of Food Microbiology,” the spores formed by Sporolactobacillus are less resistant to heat than those formed by the Bacillus genus.

Sporosarcina

Sporosarcina are a group of round-shaped (cocci) aerobic bacteria that include Sporosarcina aquimarina, Sporosarcina globispora, Sporosarcina halophila, Sporosarcina koreensis, Sporosarcina luteola and Sporosarcina ureae. According to “Antibiotic Resistance and Production in Sporosarcina ureae,” Sporosarcina is thought to play a role in the decomposition of urea in the soil.

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Revival and Identification of Bacterial Spores in
25- to 40-Million-Year-Old Dominican Amber
Raid J. Cano* and Monica K. Borucki

A bacterial spore was revived, cultured, and identified from the abdominal contents of extinct bees preserved for 25 to 40 million years in buried Dominican amber. Rigorous surface decontamination of the amber and aseptic procedures were used during the recovery of the bacterium. Several lines of evidence indicated that the isolated bacterium was of ancient origin and not an extant contaminant. The characteristic enzymatic, biochemical, and 1 6S ribosomal DNA profiles indicated that the ancient bacterium is most closely related to extant Bacillus sphaericus.

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

http://science.sciencemag.org/content/268/5213/1060.long

 

Sources:

(1)   http://Sciencing.com/types-spore-forming-bacteria-2504.html

(2) http://www.health.harvard.edu/staying-healthy/clostridium-difficile-an-intestinal-infection-on-the-rise

Clostridium difficile Research Suggests That Positively Selected Sites In the Surface Layer Proteins May Play A Role In Driving the Emergence of Hyper-virulent Strains

  • Mark Lynch,
  • Thomas A. Walsh,
  • Izabela Marszalowska,
  • Andrew E. Webb,
  • Micheál MacAogain,
  • Thomas R. Rogers,
  • Henry Windle,
  • Dermot Kelleher,
  • Mary J. O’ConnellEmail author and
  • Christine E. Loscher

To Read Abstract/Article In Its Entirety Please Click On the Following Link:

https://bmcevolbiol.biomedcentral.com/articles/10.1186/s12862-017-0937-8

 

Abstract

Background

Clostridium difficile is a nosocomial pathogen prevalent in hospitals worldwide and increasingly common in the community.

Sequence differences have been shown to be present in the Surface Layer Proteins (SLPs) from different C. difficile ribotypes (RT) however whether these differences influence severity of infection is still not clear.

Results

We used a molecular evolutionary approach to analyse SLPs from twenty-six C. difficile RTs representing different slpA sequences. We demonstrate that SLPs from RT 027 and 078 exhibit evidence of positive selection (PS).

We compared the effect of these SLPs to those purified from RT 001 and 014, which did not exhibit PS, and demonstrate that the presence of sites under positive selection correlates with ability to activate macrophages.

SLPs from RTs 027 and 078 induced a more potent response in macrophages, with increased levels of IL-6, IL-12p40, IL-10, MIP-1α, MIP-2 production relative to RT 001 and 014. Furthermore, RTs 027 and 078 induced higher expression of CD40, CD80 and MHC II on macrophages with decreased ability to phagocytose relative to LPS.

Conclusions

These results tightly link sequence differences in C. difficile SLPs to disease susceptibility and severity, and suggest that positively selected sites in the SLPs may play a role in driving the emergence of hyper-virulent strains.