CDI

C difficile: Obesity Linked to Community-Onset Infections.

Posted by

0


Obesity may be a risk factor for Clostridium difficile infection (CDI), according to results from a retrospective cohort study of 132 cases seen at a tertiary care medical center.

After potential confounders were taken into account, patients with simple community-onset infections were more than 4 times as likely to be obese as patients who had community-onset infections that came shortly after an exposure to a healthcare facility, according to data reported in an article published in the November issue ofEmerging Infectious Diseases.

“Obesity may be associated with CDI, independent of antibacterial drug or health care exposures,” write the researchers, led by Jason Leung, MD, from the University of Michigan Hospital in Ann Arbor. Such an association could help explain the uptick of community-onset cases in individuals having low levels of traditional risk factors.

The authors propose that obesity may perturb the intestinal microbiome in ways similar to those seen with inflammatory bowel disease and use of antibiotics, both of which are known risk factors for CDI.

“Translational research could help elaborate the dimensions of the interaction of the intestinal microbiota with C. difficile in obese patients,” the researchers maintain. They also suggest that an investigation of a dose–response relationship between body mass index and infection risk might be informative.

“[I]t is critical to establish whether obesity is a risk factor for high rates of C. difficile colonization, as is [inflammatory bowel disease]; if that risk factor is established, prospective observations would improve understanding of whether obesity plays a role in the acquisition of CDI, or alters severity of disease and risk for recurrence,” they write.

As for the patients with community-onset infections after healthcare exposure, the study’s findings highlight “the importance of increased infection control at ancillary health care facilities and surveillance for targeting high-risk patients who were recently hospitalized.”

In the study, the researchers reviewed the microbiology results and medical records of all patients who had laboratory-proven, nonrecurrent CDI at Boston Medical Center in Massachusetts during a 6-month period.

When the patients were classified according to the setting of disease onset, 43% had infections that began in the community without recent exposure to a healthcare facility, 30% had infections that began in a healthcare facility, and 23% had infections that began in the community within 30 days of exposure to a healthcare facility (most often a hospital or long-term care facility).

The prevalence of obesity, defined as a body mass index exceeding 30 kg/m2, was 34% in the group with community-onset infections compared with 23% in the general population (odds ratio, 1.7; 95% confidence interval [CI], 1.02 – 2.99). The value stood at 13% in the group with community-onset healthcare-associated infections and 32% in the group with healthcare-onset infections.

In multivariate analyses, patients with simple community-onset infections were significantly less likely to be older than 65 years (odds ratio, 0.35; 95% CI, 0.13 – 0.92; P < .05) and more likely to be obese (odds ratio, 4.06; 95% CI, 1.15 – 14.36; P < .05) than patients with community-onset healthcare-associated infections.

In addition, patients with simple community-onset infections were significantly less likely to have prior antibiotic exposure (odds ratio, 0.29; 95% CI, 0.11 – 0.76; P < .05) than patients with healthcare-onset infections. There was also a trend whereby they were much more likely to have inflammatory bowel disease (odds ratio, 6.40; 95% CI, 0.73 – 56.17; P < .10).

Finally, patients with community-onset healthcare-associated infections were dramatically less likely to have had prior antibiotic exposure than patients with healthcare-onset infections (odds ratio, 0.08; 95% CI, 0.02 – 0.28; P < .05).

Antibiotics for All but Very Mild C difficile.

Posted by

0


On October 29, the European Society of Clinical Microbiology and Infection (ESCMID) issued updated guidelines for Clostridium difficile infection (CDI), reviewing treatment options of antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and fecal or bacterial intestinal transplantation. The new recommendations, published online October 5 in Clinical Microbiology and Infection, advise antibiotic treatment for all but very mild cases of CDI.

CDI, which is potentially fatal, is now the leading cause of healthcare-acquired infections in hospitals, having surpassed methicillin-resistant Staphylococcus aureus.

“[A]fter the recent development of new alternative drugs for the treatment of CDI (e.g. fidaxomicin) in US and Europe, there has been an increasing need for an update on the comparative effectiveness of the currently available antibiotic agents in the treatment of CDI, thereby providing evidence-based recommendations on this issue,” write Sylvia B. Debast, from the Centre for Infectious Diseases, Leiden University Medical Center The Netherlands, and colleagues from the ESCMID Committee.

The new guideline, which updates the 2009 ESCMID recommendations now used widely in clinical practice, summarizes currently available CDI treatment options and offers updated treatment recommendations on the basis of a literature search of randomized and nonrandomized trials.

The ESCMID and an international team of experts from 11 European countries developed recommendations for different patient subgroups, including initial nonsevere disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences, and treatment of CDI when patients cannot receive oral antibiotics.

Antibiotic Recommended in Most Cases

Specific recommendations include the following:

·         For nonepidemic, nonsevere CDI clearly induced by antibiotic use, with no signs of severe colitis, it may be acceptable to stop the inducing antibiotic and observe the clinical response for 48 hours. However, patients must be monitored very closely and treated immediately for any signs of clinical deterioration.

·         Antibiotic treatment is recommended for all cases of CDI except for very mild CDI, which is actually triggered by antibiotic use. Suitable antibiotics include metronidazole, vancomycin, and fidaxomicin, a newer antibiotic that can be given by mouth.

·         For mild/moderate disease, metronidazole is recommended as oral antibiotic treatment of initial CDI (500 mg 3 times daily for 10 days).

·         Fidaxomicin may be used in all CDI patients for whom oral antibiotic treatment is appropriate. Specific indications for fidaxomicin may include first-line treatment in patients with first CDI recurrence or at risk for recurrent disease, in patients with multiple recurrences of CDI, and in patients with severe disease and nonsevere CDI.

These recommendations were based on 2 large phase 3 clinical studies that compared 400 mg/day oral fidaxomicin with 500 mg/day oral vancomycin, the standard of care. The rate of CDI recurrence was lower with fidaxomicin, but the cure rate was similar for both treatments.

·         For severe CDI, suitable oral antibiotic regimens are vancomycin 125 mg 4 times daily (may be increased to 500 mg 4 times daily) for 10 days, or fidaxomicin 200 mg twice daily for 10 days.

·         In life-threatening CDI, there is no evidence supporting the use of fidaxomicin.

·         In severe CDI or life-threatening disease, the use of oral metronidazole is strongly discouraged.

·         For multiple recurrent CDI, fecal transplantation is strongly recommended.

·         Total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended for CDI with colonic perforation and/or systemic inflammation and deteriorating clinical condition despite antibiotic treatment.

·         Additional measures for CDI management include discontinuing unnecessary antimicrobial therapy, adequate fluid and electrolyte replacement, avoiding antimotility medications, and reviewing proton pump inhibitor use.

Novel Strategy for Preventing CDI.

Posted by

0


 

Antigermination therapy prevented disease in mice challenged with massive inocula of C. difficile spores.

Spore germination is necessary for the development of symptomatic Clostridium difficile infection (CDI). Recent investigations have yielded novel nonantibiotic agents that inhibit spore germination mediated by taurocholate, a bile salt. To determine whether CamSA — a taurocholate analog that inhibits germination in vitro — might prevent CDIs, researchers conducted experiments using a mouse model.

Mice received an antibiotic “cocktail” in their drinking water for 3 days, and then a single dose of intraperitoneally administered clindamycin on day 4. The animals, in groups of five, each received 0 mg/kg, 5 mg/kg, 25 mg/kg, or 50 mg/kg of CamSA by oral gavage, followed on day 5 by gavage challenge with a massive dose of C. difficile spores and additional doses of CamSA 1 and 24 hours thereafter. The mice were then monitored for clinical evidence of CDI, and disease signs were scored. Some animals in each group were sacrificed and underwent postmortem examination of the gastrointestinal tract.

All animals that received 0 mg/kg of CamSA developed severe CDI within 48 hours of spore inoculation. In contrast, those that received 50 mg/kg showed no clinical or histopathologic evidence of CDI. Animals that received either 5 mg/kg or 25 mg/kg had a delayed onset of CDI and a reduction in disease severity. The excretion of cells and spores in feces also correlated with CamSA dose: Vegetative cells predominated in animals in the untreated (0-mg/kg) and 5-mg/kg groups, whereas spores predominated in those in the 25-mg/kg and 50-mg/kg groups.

Although CamSA (3 doses at 50 mg/kg) was protective in mice challenged with spores, it was ineffective in preventing CDI in animals challenged with vegetative cells.

Comment: These findings in a murine model deserve special attention. The novel, nonantibiotic strategy studied could be a “game changer” as we consider potential approaches for CDI management. As the authors note, patients determined to be at risk for CDI could receive CamSA before initiating antibiotics, then additional doses as needed until the intestinal microbiota has recovered.

Source: Journal Watch Infectious Diseases