Posts Tagged ‘Clostridium difficile’

Reporter and Curator: Dr. Sudipta Saha, Ph.D.


Clostridium difficile-associated disease, a significant problem in healthcare facilities, causes an estimated 15,000 deaths in the United States each year. Clostridium difficile, commonly referred to as C. diff, is a bacterium that infects the colon and can cause diarrhea, fever, and abdominal pain. Clostridium difficile-associated disease (CDAD) most commonly occurs in hospitalized older adults who have recently taken antibiotics. However, cases of CDAD can occur outside of healthcare settings as well.


Although antibiotics often cure the infection, C. diff can cause potentially life-threatening colon inflammation. People with CDAD usually are treated with a course of antibiotics, such as oral vancomycin or fidaxomicin. However, CDAD returns in approximately 20 percent of people who receive such treatment, according to the Centers for Disease Control and Prevention (CDC).


Multiple research studies have indicated that fecal microbiota transplantation (FMT) is an effective method for curing patients with repeat C. diff infections. However, the long-term safety of FMT has not been established. Although more research is needed to determine precisely how FMT effectively cures recurrent CDAD, the treatment appears to rapidly restore a healthy and diverse gut microbiome in recipients. Physicians perform FMT using various routes of administration, including oral pills, upper gastrointestinal endoscopy, colonoscopy, and enema.


A research consortium recently began enrolling patients in a clinical trial examining whether FMT by enema (putting stool from a healthy donor in the colon of a recipient) is safe and can prevent recurrent CDAD, a potentially life-threatening diarrheal illness. Investigators aim to enroll 162 volunteer participants 18 years or older who have had two or more episodes of CDAD within the previous six months.


Trial sites include Emory University in Atlanta, Duke University Medical Center in Durham, North Carolina, and Vanderbilt University Medical Center in Nashville, Tennessee. Each location is a Vaccine and Treatment Evaluation Unit (VTEU), clinical research sites joined in a network funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. This randomized, controlled trial aims to provide critical data on the efficacy and long-term safety of using FMT by enema to cure C. diff infections.


Volunteers will be enrolled in the trial after completing a standard course of antibiotics for a recurrent CDAD episode, presuming their diarrhea symptoms cease on treatment. They will be randomly assigned to one of two groups. The first group (108 people) will take an anti-diarrheal medication and receive a stool transplant (FMT) delivered by retention enema. The second group (54 people) will take an anti-diarrheal medication and receive a placebo solution delivered by retention enema.


Participants in either group who have diarrhea with stools that test positive for C. diff shortly after the enema will be given an active stool transplant for a maximum of two FMTs. If participants in either group have another C. diff infection after receiving two FMTs, then they will be referred to other locally available treatment options. Investigators will evaluate the stool specimens for changes in gut microbial diversity and infectious pathogens and will examine the blood samples for metabolic syndrome markers.


To learn more about the long-term outcomes of FMT, the researchers will monitor all participants for adverse side effects for three years after completing treatment for recurrent CDAD. Investigators will also collect information on any new onset of CDAD, related chronic medical conditions or any other serious health issues they may have.




















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LytPhage Presents at 1st Pitch Life Sciences-Philadelphia-September 16, 2014

Reporter: Stephen J. Williams, PhD


LytPhage presented at Mid-Atlantic BioAngels 1st Pitch Life Sciences in  Philadelphia Tuesday Sept. 16, 2014.

LytPhage is a new biotech company using novel bioengineering to develop therapeutics to address the worldwide crisis of antibiotic resistant organisms.  They are developing a treatment for vancomycin resistant systemic infections with their platform, which can be adapted for other problematic organisms.  LytPhage is a spin-out form Temple University.

The overall goal is to use genetically modified bacteriophage (bacterial viruses) as an antimicrobial therapy against drug-resistant strains.  Their genetically modifed viruses are only lytic, meaning they result in cell death of the host but do not integrate in the host DNA.  In additon preliminary studies using mainly clinical isolates have shown good efficacy against most drug-resistant strains found in common hospital infections like Clostridium difficile colitis.  The presenters noted that bacteriophage therapy had successfully been used in Europe but no approved therapy in US

For more information about this meeting please see posting on this site

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High Risk of Transmissible Disease and Mortality in Cancer, Advanced Cardiovascular Disease, and Hemodialysis Patients

Curator: Larry H Bernstein, MD, FCAP

This contribution is aimed at three situations of special concern with respect to transmission and handling of episodic bacteria or virus spread in hospital and ambulatory healthcare settings, where healthcare workers may be exposed and either become ill or are potential carriers of the disease.  Not discussed is a report in the last week of an association between human papilloma virus (HPV), known to be associated with cervical cancer, and oropharyngeal cancer.   In all of these situations, the patients at highest risk of death are immune compromized, carry a heavy burden of unbalanced oxidative stress, and have mitcochondrial dysfunction from unbalanced ubiquitination and repair.

Clostridium Difficile Colitis

Faten N Aberra, MD, MSCE; Chief Editor: Julian Katz, MD
Medscape – Practice Essentials

Clostridium difficile colitis results from a disturbance of the normal bacterial flora of the colon, colonization by C difficile, and the release of toxins that cause mucosal inflammation and damage. Antibiotic therapy is the key factor that alters the colonic flora. C difficile infection primarily occurs in hospitalized patients.

Essential update: Fidaxomicin superior to vancomycin for cancer patients with C difficile

In a multicenter study including 1105 subjects with C difficile – associated diarrhea, 183 of whom had solid tumors or hematologic malignancies, fidaxomicin treatment was superior to vancomycin treatment in cancer patients, resulting in higher cure and sustained response rates, shorter time to resolution of diarrhea (TTROD), and fewer recurrences.  Cure rates were lower overall in cancer patients than in others (79.2% vs 88.6%; P < 0.001).[2Whereas cure rates for noncancer patients were approximately the same with fidaxomicin as with vancomycin (88.5% vs 88.7%), those for cancer patients were higher with fidaxomicin than with vancomycin (85.1% vs 74.0%), though the difference was not statistically significant. Median TTRODs in noncancer patients were 54 hours with fidaxomicin and 58 with vancomycin; those in cancer patients were 74 and 123 hours, respectively.  The risk of recurrence was approximately twice as high with vancomycin as with fidaxomicin, regardless of whether patients had cancer or not, but because both cure and recurrence outcomes were better with fidaxomicin than with vacomycin in cancer patients, the relative odds of sustained response at 28 days in these patients were more than 2.5-fold higher for fidaxomicin than for vancomycin.


Clostridium difficile is a gram-positive, anaerobic, spore-forming bacillus that is responsible for the development of antibiotic-associated diarrhea and colitis. C difficile was first described in 1935 as a component of the fecal flora of healthy newborns and was initially not thought to be a pathogen. It was named difficile because it grows slowly and is difficult to culture. While early investigators noted that the bacterium produced a potent toxin, the role of C difficile in antibiotic-associated diarrhea and pseudomembranous colitis was not elucidated until the 1970s.
Approximately 20% of individuals who are hospitalized acquire C difficile during hospitalization, and more than 30% of these patients develop diarrhea. Thus, C difficile colitis is currently one of the most common nosocomial infections.
The diagnosis of C difficile colitis should be suspected in any patient with diarrhea who has received antibiotics within the previous 2 months and/or when diarrhea occurs 72 hours or more after hospitalization.


Colonization occurs by the fecal-oral route. C difficile forms heat-resistant spores that can persist in the environment for several months to years. Outbreaks of C difficile diarrhea may occur in hospitals and other outpatient facilities where contamination with spores is prevalent. Normal gut flora resists colonization and overgrowth with C difficile. Antibiotic use, which suppresses the normal flora, allows proliferation of C difficile.
Pathogenic strains of C difficile produce 2 distinct toxins. Toxin A is an enterotoxin, and toxin B is a cytotoxin. Both are high–molecular weight proteins capable of binding to specific receptors on the intestinal mucosal cells. Receptor-bound toxins gain intracellular entry where they catalyze a specific alteration of Rho proteins, small glutamyl transpeptidase (GTP)–binding proteins that assist in actin polymerization, cytoskeletal architecture, and cell movement. Both toxin A and toxin B appear to play a role in the pathogenesis of C difficile colitis in humans.


Although the incidence of other nosocomial infections declined from 2000-2009, the number of hospitalized patients with any C difficile infection discharge diagnosis more than doubled, from approximately 139,000 to 336,600. The number of patients with a primary C difficile infection diagnosis more than tripled, from 33,000 to 111,000.
Among C difficile infections identified in the Centers for Disease Control and Prevention’s (CDC’s) Emerging Infections Program data in 2010, 94% were associated with receiving health care; of these, 75% had onset among persons not currently hospitalized, including recently discharged patients, outpatients, and nursing home residents



Physical examination may reveal the following in patients with the disorder:
  • Fever: Especially in more severe cases
  • Dehydration
  • Lower abdominal tenderness
  • Rebound tenderness: Raises the possibility of colonic perforation and peritonitis

Laboratory studies

  • Lab tests for evaluating patients with C difficile infection include the following:
  • Electrolytes: Dehydration and electrolyte imbalance may accompany severe disease
  • Albumin: Hypoalbuminemia and anasarca may accompany severe disease
    • Transthyretin is the serum protein of choice for a rapid onset diarrhea with dehydration leading to weight loss, dehydration, anasarca and sarcopenia, as it has a serum half-life of ~ 48 hrs rather than 21 days, and it is an accurate measure of lean body mass.
  • Complete blood count: Leukocytosis may be present
  • Stool examination: Stool may be Hemoccult positive in severe colitis, but grossly bloody stools are unusual; fecal leukocytes are present in about half of cases
  • Stool assays for C difficile, from the most to the least sensitive, include the following:
  1. Stool culture: The most sensitive test (sensitivity, 90-100%; specificity, 84-100%), but the results are slow and may lead to a delay in the diagnosis if used alone
  2. Glutamate dehydrogenase enzyme immunoassay (EIA): Very sensitive (sensitivity, 85-100%; specificity, 87-98%); this test detects the presence of glutamate dehydrogenase produced by C difficile
  3. Real-time polymerase chain reaction (PCR) assay: May be used to detect C difficile gene toxin
  4. The stool cytotoxin test: Has a sensitivity of 70-100% and a specificity of 90-100%; a positive test result is the demonstration of a cytopathic effect that is neutralized by a specific antiserum
  5. Enzyme immunoassay for detecting toxins A and B: Used in most labs; the sensitivity is moderate (79-80%), and the specificity is excellent (98%)
  6. Latex agglutination technique: Another means of detecting glutamate dehydrogenase; the sensitivity of this test is poor (48-59%), although the specificity is 95-96%


Treatment for C difficile infection varies according to its severity. Interventions include the following:
  • Asymptomatic carriers: No treatment necessary
  • Mild, antibiotic-associated diarrhea without fever, abdominal pain, or leukocytosis: Cessation may be the only treatment necessary
  • Mild to moderate diarrhea or colitis: Metronidazole (oral or intravenous) or vancomycin (oral) for 10 days
Severe disease: Vancomycin is considered to produce faster symptom resolution and fewer treatment failures than metronidazole; in fulminant cases, combined therapy with intravenous metronidazole and oral vancomycin may be considered


Relapse occurs in 20-27% of patients treated with metronidazole or vancomycin. Once a patient has one relapse, the risk for a second relapse is 45%. Relapses should be treated as follows:
  • First relapse: The choice of antibiotic should be based on the severity of C difficile diarrhea/colitis
  • Subsequent relapses: For every relapse beyond the first, vancomycin (prolonged taper/pulsed regimen) is recommended to help clear persistent spores
Among various investigational therapies, fecal transplantation (fecal enemas or infusion of donor feces through a nasoduodenal tube) has been reported to repopulate the colonic flora and treat recurrent C difficile infection.

Staphylococcus Aureus Infection

Robert W Tolan Jr, MD; Chief Editor: Russell W Steele, MD

Rise of methicillin and vancomycin-resistance

Both community-associated and hospital-acquired infections with Staphylococcus aureus have increased in the past 20 years, and the rise in incidence has been accompanied by a rise in antibiotic-resistant strains—in particular, methicillin-resistant S aureus (MRSA) and, more recently, vancomycin-resistant strains.

Essential update: Universal decolonization more effective than screening and isolation in reducing rates of MRSA

Daily washing of ICU patients with chlorhexidine-impregnated cloths reduced positive cultures of MRSA by 37% and reduced bloodstream infection by any pathogen by 44%, according to a study of 74,256 patients in 74 adult ICUs.
In the study, hospitals were randomized to 18 months of either screening for MRSA followed by isolation of positive patients, targeted decolonization of MRSA-positive patients and isolation, or universal decolonization of all ICU patients without screening. Decolonization was achieved via daily cleansing with chlorhexidine-impregnated cloths and 5 days of twice-daily intranasal mupirocin treatments. At baseline, there was no significant difference in the rate of MRSA infections between the 3 groups.  However, patients who underwent universal decolonization showed a significantly larger decline between baseline and intervention periods than those in either of the targeted interventions. Universal decolonization led to a 37% drop in the rate of MRSA infections, while targeted decolonization led to a 25% decline and no significant change was seen in the screening and isolation group. There was no significant difference in outcomes between the targeted decolonization and the screening and isolation groups, while the difference between the universal decolonization and the screening and isolation groups was significant (P = .003). Universal decolonization also significantly reduced ICU-attributed bloodstream infections from any pathogen.


Antibiotic regimens include the following:
  • Empiric therapy with penicillins or cephalosporins may be inadequate because of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
  • Combination therapy with a penicillinase-resistant penicillin or cephalosporin (in case the organism is methicillin-sensitive S aureus [MSSA]) and clindamycin or a quinolone
  • Clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), rifampin, doxycycline, or a quinolone
  • TMP-SMX and rifampin in combination, rather than singly
Clindamycin (rather than TMP-SMX) may become the preferred outpatient antibiotic therapy in regions with a relatively low incidence of clindamycin resistance
The Infectious Diseases Society of America has published treatment guidelines for MRSA infection


Daptomycin, with or without beta-lactams, controls S aureus bacteremia without worsening renal dysfunction. In a cohort of patients with mild or moderate renal insufficiency, more than 80% responded to treatment, with no detrimental effect on their kidneys. Currently, the combination of daptomycin with beta-lactams is recommended only as salvage therapy for refractory MRSA bacteremia. 

New Coronavirus ‘Eerily’ Like SARS

By Michael Smith, North American Correspondent, MedPage   June 19, 2013
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

The novel coronavirus outbreak in the Middle East is eerily similar to SARS, according to Trish Perl, MD, of the Johns Hopkins University School of Medicine, part of an international team, led by Ziad Memish, MD, of the World Health Organization in Riyadh, that looked into a cluster of 23 cases in hospitals in the east of Saudi Arabia. . “The illness pattern, the incubation period — there are a lot of eerie similarities,” Perl told MedPage Today. They reported online in the New England Journal of Medicine, that the virus, MERS-CoV, is related to the virus that caused the 2002-2003 SARS outbreak.  The viruses both are coronaviruses and both lead to severe respiratory illness. Further, person-to-person transmission can take place in healthcare settings and can do so with “considerable morbidity.”  One key difference, Perl and colleagues noted, is that — at least in the cluster they investigated — the fatality rate was 65%, markedly higher than the 8% or so seen in the SARS outbreak. On the other hand, that rate may fall if a large number of milder cases is detected, they noted.  An outside expert, David Freedman, MD, of the University of Alabama at Birmingham, told MedPage Today that an open question has been whether MERS could spread within hospitals as easily as did SARS.  The current study, he said, shows “unequivocally” that it can.
The report comes as the World Health Organization is reporting a total of 64 laboratory-confirmed cases of infection with MERS-CoV, including 38 deaths. Most reported cases have either occurred in the Middle East or have involved recent travel to the region.  SARS was contained and eventually controlled by identifying cases vigorously and then isolating them to prevent transmission, Perl noted, and similar tactics — when they were applied in Saudi Arabia — appeared to have the same effect. The key in the epidemiological chain may have been Patient C, who had been undergoing long-term hemodialysis, and was admitted to hospital April 6 in the room next to Patient A.  When Patient A developed a fever April 8, Patient C was still in the same room and developed fever himself 3 days later. He also had dialysis in the hospital’s outpatient hemodialysis unit twice after the onset of symptoms. Between April 14 and April 30, MERS was confirmed in nine more patients who were undergoing hemodialysis, including six who did so at times overlapping those of Patient C. All told, Patient C appears to have transmitted MERS directly to seven people, six in the dialysis unit and one in the intensive care unit, the researchers reported, while other infected people had more limited transmission and some did not pass on the disease at all.

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