New C. diff treatment reduces recurrent infections by 40 percent

This photograph depicts Clostridium difficile colonies after 48hrs growth on a blood agar plate; Magnified 4.8X. C. difficile, an anaerobic gram-positive rod, is the most frequently identified cause of antibiotic-associated diarrhea (AAD). It accounts for approximately 15-25% of all episodes of AAD. Credit: CDC

A new treatment for Clostridium difficile (C.diff) infections reduces recurrent infections by nearly 40%, a large study has found.

29 jan 2017--C.diff, a bacterium that infects the bowel, is the most common cause of infectious diarrhea in hospitalised patients. Recurrences are common after antibiotic treatment, are a cause of readmissions to hospital, and in some cases can be fatal.
Now a team of researchers have found that the addition of a drug called bezlotoxumab (Merck) to standard antibiotic treatment can reduce the risk of a repeat infection by 37%. Bezlotoxumab is a human monocalonal antibody and works by neutralising a toxin produced by the C.diff bacteria that damages the gut wall.
Mark Wilcox, Professor of Microbiology at the University of Leeds, led the study, which is published today in the New England Journal of Medicine.
Professor Wilcox said: "About one in four patients who have been treated with antibiotics for an initial C.diff infection will go on to have a repeat infection.
"These repeat infections are more difficult to treat, have more severe outcomes for the patient, and are associated with more hospitalisations. It is important to treat the first episodes of C. diff infection optimally, as each recurrence increases the chance of another episode even more.
"Fewer recurrent infections would mean less need to use antibiotics, fewer hospital admissions, reduced costs for the NHS and possibly a reduction in deaths."
For the study, doctors conducted a double-blind, randomised, placebo-controlled trial involving 2,655 adults across over 300 hospitals in 30 countries worldwide.
All the participants had primary or recurrent C.diff infections and were receiving standard-of-care antibiotics (metronidazole, vancomycin or fidaxomicin).
They were randomly assigned to receive infusions of:
- a single dose of (another human monocalonal antibody) actoxumab (10mg per kilogram of body weight)
- a single dose of bezlotoxumab (10mg per kilogram of body weight)
- a single dose of bezlotoxumab plus actotoxumab (10mg per kg of body weight)
- a placebo (saline)
After initial cure of their C.diff, the patients were then followed up for 12 weeks to see how many developed another C.diff infection.
- In the actoxumab group, 26% developed another C.diff infection
- In the bezlotoxumab group, 17% developed another C.diff infection
- In the bezlotoxumab/actotoxumab group, 15% developed another C.diff infection
- In the placebo group, 27% developed another C.diff infection.
"Doctors should now consider which patients could best benefit from use of bezlotoxumab," said Professor Wilcox.
"The studies showed that bezlotoxumab was particularly effective in those patients with risk factors for poor outcome, including older age, immunocompromise, and severe infection."

More information: New England Journal of Medicine, DOI: 10.1056/NEJMoa1602615


Provided by University of Leeds

Gut superbug causing more illnesses, deaths

By MIKE STOBBE
29 may 2008--The number of people hospitalized with a dangerous intestinal superbug has been growing by more than 10,000 cases a year, according to a new study.
The germ, resistant to some antibiotics, has become a regular menace in hospitals and nursing homes. The study found it played a role in nearly 300,000 hospitalizations in 2005, more than double the number in 2000.
The infection, Clostridium difficile, is found in the colon and can cause diarrhea and a more serious intestinal condition known as colitis. It is spread by spores in feces. But the spores are difficult to kill with most conventional household cleaners or antibacterial soap.
C-diff, as it's known, has grown resistant to certain antibiotics that work against other colon bacteria. The result: When patients take those antibiotics, competing bacteria die off and C-diff explodes.
This virulent strain of C-diff was rarely seen before 2000.
"The nature of this infection is changing. It's more severe," said Dr. L. Clifford McDonald, a Centers for Disease Control and Prevention expert who was not part of the study.
There are other factors that play into the rise of C-diff cases as well, including a larger of number of patients who are older and sicker. "And there may be some overuse and inappropriate use of antibiotics," said Dr. Marya Zilberberg, a University of Massachusetts researcher and lead author of the study.
The Zilberberg study was based on a sample of more than 36 million annual discharges from non-governmental U.S. hospitals. That data was used to generate the study's national estimates.
The research is being published in the June issue of Emerging Infectious Diseases, a CDC publication.
Using other scientists' estimates, the study concluded that 2.3 percent of the cases in 2004 were fatal — about 5,500 deaths. That was nearly double the percentage of C-diff-related cases that ended in death in 2000.
Many of the people who died had other health problems. The study did not try to determine if Clostridium difficile was the main cause of death in each case, Zilberberg said.
But earlier research concluded the infection is the underlying cause of thousands of deaths annually, and the problem is getting worse.
C-diff has become an acute health concern in Canada, where it was blamed for 260 deaths at seven Ontario hospitals recently, and 2,000 deaths in Quebec since 2002.
The Association for Professionals in Infection Control and Epidemiology is currently working with U.S. hospitals to study prevalence of the infection and what infection control measures seem to work best.
"This is not a time for alarm, but more a time for educating health professionals to understand this particular pathogen," said Kathy Warye, chief executive of the Washington, D.C.-based association.

Rising Case Rate and Mortality Documented for C. difficile Colitis

MINNEAPOLIS, July 16 -- The frequency and severity of Clostridium difficile colitis in hospitalized patients have increased dramatically since the early 1990s, leading to greater morbidity and mortality, investigators here reported.
From 1993 through 2003 the number of reported cases of C. difficile colitis in hospitalized patients doubled, associated mortality increased by 150%, and the number of colectomies attributable to the infection increased by 50%, according to an article in the July issue of Archives of Surgery.
Frequency and mortality increased every calendar year (P<0.05 to P<0.001), reported Rocco Ricciardi, M.D., M.P.H, and colleagues, of the University of Minnesota.
Although the reasons for the rising volume of cases remain unclear, they said, the data "provide compelling evidence of the changing epidemiological features of C. difficile colitis."
C. difficile is found in the intestinal tract of 1% to 3% of healthy adults and in about 20% of patients on antibiotics. A subset of patients becomes symptomatic when native colonic flora are altered or overtaken by C. difficile. An estimated 3 million new cases of C. difficile colitis occur each year, including as many as 10% of patients hospitalized for at least two days.
Several recent reports have documented an increased incidence, and possibly increased severity, of C. difficile colitis. In an effort to clarify anecdotal and case series findings, the investigators reviewed hospital discharge data from the Agency for Healthcare Research and Quality for the period of Jan. 1, 1993 through Dec. 31, 2003.
ICD-9 codes were used to identify patients with a primary or secondary diagnosis of C. difficile colitis. The analysis revealed 299,453 cases, for which the investigators calculated total mortality, case fatality rate, and the colectomy rate associated with C. difficile colitis.
During the 11-year review period, the C. difficile colitis case rate increased from 261.0 per 100,000 to 546.0 per 100,000 (P<0.001).
Total mortality increased from 20.3 per 100,000 cases in 1993 to 50.2 per 100,000 in 2003 (P<0.001).
The case fatality rate increased from 7.8 per 100 to 9.3 per 100 (P<0.001).
The colectomy rate rose from 1.2 per 1,000 cases to 3.4 per 1,000 (P<0.001).
Selected other findings include:
There was a higher case rate in female patients but a higher mortality and colectomy rate in men.
There was a higher case rate and mortality in Medicare patients compared to all others, but a higher colectomy rate in patients with private insurance or self-pay.
Case rate and mortality increased with the number of comorbidities.
Case rate, case fatality rate, and mortality all increased with age, but the colectomy rate peaked in patients ages 60 to 69 and then decreased in older patients.
The study did not permit determination of the causes of the changing epidemiology of C. difficile colitis. The authors noted, however, that some recent epidemics have been linked to hypervirulent strains of the bacteria. Other possible explanations, they said, include increased resistance to first-line antibiotic therapy, increased use of fluoroquinolone antibiotics, and increased acuity of hospitalized patients.
In a critique that accompanied the article, Susan L. Gearhart, M.D., of Johns Hopkins, said the study emphasized the importance of judicious use of antibiotics.
"As physicians and surgeons, we cannot emphasize enough how important it is to limit the use of these antibiotics to known bacterial infections," wrote Dr. Gearhart. "In surgical prophylaxis, standardization of antibiotic type and length of perioperative coverage should be implemented in U.S. health systems. Actions such as this may help limit the prevalence of this disease."
Dr. Ricciardi, currently of the Lahey Clinic in Burlington, Mass., and the other authors had no financial disclosures. The study was supported by a grant from the University of Minnesota. Dr. Gearhart had no disclosures. Additional source: Archives of SurgerySource reference: Ricciardi R et al. "Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States." Arch Surg 2007; 142:624-631.