Worrisome increase in multiply recurrent C. difficile cases

Last Updated: 2017-07-03

By Will Boggs MD

NEW YORK (Reuters Health) - The incidence of multiply recurrent Clostridium difficile infection (mrCDI) increased more than four times as fast as that of isolated CDI between 2001 and 2012, according to a retrospective study.

"While we did expect to find that the incidence of multiply-recurrent CDI has increased over time, the degree to which it increased out of proportion to the increase of non-multiply-recurrent CDI incidence was surprising,” Dr. Gene K. Ma from the University of Pennsylvania Perelman School of Medicine in Philadelphia told Reuters Health by email. “These findings underscore the need for further research in multiply-recurrent CDI therapeutics, including fecal microbiota transplantation (FMT).”

CDI is the most common healthcare-associated infection, and treatment with FMT, an expensive and largely unregulated therapy, can only add to the estimated $5 billion annual cost of CDI to the US healthcare system, he and colleagues write July 3rd online in Annals of Internal Medicine.

Dr. Ma's team studied data from the OptumInsight Clinformatics Database, which contains information on insured patients from several health plans in the U.S.

Based on information on nearly 39 million patients, the annual incidence of CDI increased by 42.7% between 2001 and 2012 (from 0.4408 to 0.6289 case per 1000 person-years).

During the same interval, the annual incidence of mrCDI increased by 188.8% (from 0.0107 to 0.0309 case per 1000 person-years), according to the report.

The risk of mrCDI increased by 25% for each 10-year increase in age and was 24% more likely in females than in males. Other independent predictors of an increased risk for mrCDI included the use of antibiotics other than those used to treat CDI, proton pump inhibitors (PPIs), and corticosteroids, as well as a diagnosis of chronic kidney disease (but not of inflammatory bowel disease or diabetes).

Being in a nursing home nearly doubled the risk of mrCDI.

“While our study evaluated risk factors for development of multiply-recurrent CDI, further research in this area will be necessary to define the patient population at highest risk for multiply-recurrent CDI development,” Dr. Ma said. “Ultimately, these patients may benefit from different treatment guidelines, including earlier use of fecal microbiota transplantation or antibiotics such as vancomycin or fidaxomicin.”

“Multiply-recurrent CDI is a growing public health issue that many physicians will encounter in their practice,” he said. “Physicians should be familiar with both CDI diagnostic tools to determine if patients truly have recurrent CDI and also multiply-recurrent CDI therapeutics as their use will likely increase over time.”

Dr. Sameer D. Saini from VA Ann Arbor Center for Clinical Management Research and the University of Michigan, who co-wrote an editorial related to this report, told Reuters Health by email, "While the absolute increase is low in this cohort (due to the low overall prevalence in this younger population), the rate of increase (especially if replicated in higher prevalence populations, such as older adults) indicates that mrCDI is, or is likely to become, a serious issue for at-risk patients in the United States.”

“The primary way to prevent mrCDI is through traditional infection control practices (e.g., hand washing, contact precautions) and antibiotic stewardship (reducing unnecessary use of antibiotics and restricting the use of specific antibiotics),” he said. “These practices not only prevent incident infections - they also prevent recurrences (and by inference, multiple recurrences). Minimizing unnecessary use of proton pump inhibitors may also be helpful.”

“In the future,” Dr. Saini added, “prediction models could help us identify who is at high risk for developing mrCDI and target novel therapies to those most likely to benefit.”

“A better understanding of the epidemiology of mrCDI is a critical first step toward developing a sound strategy to address this growing public health challenge,” write Dr. Saini and coauthor Dr. Akbar K. Waljee in their editorial.

“We were fooled in the 1930s, when we wrongly concluded that C. difficile was unlikely to be pathogenic, and again in the 1980s and 1990s, when we saw this infection as a mere nuisance for the hospitalized patient,” they note. “We cannot afford to be fooled a third time when it comes to this important condition.”

Dr. Ashwin Ananthakrishnan from the Massachusetts General Hospital in Boston, who has researched various aspects of CDI, told Reuters Health by email, "The most surprising finding is that the rise in multiply recurrent CDI is much greater than that for CDI in general, suggesting this population may be unique in their risk factor distribution and characterization.”

“There are a number of modifiable risk factors that the authors identify (antibiotics, PPI, steroid use) which could be minimized to reduce burden due to mrCDI,” he said. “It also suggests that more effective treatments for mrCDI need to be used earlier on in the disease to reduce the burden.”

Dr. Lena Napolitano from the University of Michigan in Ann Arbor, who has reviewed the diagnosis, epidemiology, and treatment of CDI, said by email, "The definition of CDI ‘relapse’ vs. ‘reinfection’ is very important for CDI surveillance, but is controversial. The mrCDI definition used in this current study is not based on patient symptoms or CDI testing related to administrative claims data used in the study - it is only based on an ICD-9 diagnosis code or CPT CDI testing code (without knowing the results) and CDI prescribed treatment. And it is not possible to determine whether these recurrence CDI cases are ‘relapse’ vs. ‘reinfection.’”

“So even with this publication I am still uncertain what the CDI recurrence/relapse/reinfection rate is in the US,” she said.

Dr. Napolitano mentioned fidaxomicin, bezlotoxumab, FMT, and probiotics as possible treatments, but concluded that “there are no rigorous clinical trials of management for mrCDI, so we do not know which of these agents is the most effective treatment in patients with mrCDI.”

SOURCE: http://bit.ly/2sGjn3w

Ann Intern Med 2017.