In the JournalsPerspective

Rise in multiply recurrent C. difficile increases demand for therapies

Between 2001 and 2011, the incidence of multiply recurrent Clostridium difficile infection increased significantly, which will likely increase the demand for therapies — such as fecal microbiota transplantation — to treat the condition, according to research published in Annals of Internal Medicine.

“Incidence of [Clostridium difficile] is widely believed to have increased over the past 2 decades, with hospitalizations for the infection in the United States doubling between 2000 and 2010,” Gene K. Ma, MD, from the University of Pennsylvania Perelman School of Medicine, and colleagues wrote. “However, little is known about trends in incidence of recurrent CDI, particularly [multiply recurrent CDI (mrCDI)], which would be an indication for [fecal microbiota transplantation (FMT)]. Knowledge of the magnitude of this problem and projection of the potential demands on the health care system in the coming years are needed.”

Ma and colleagues conducted a retrospective cohort study to investigate whether the occurrence of mrCDI is increasing in proportion to CDI, as well as to identify risk factors for mrCDI. Using the OptumInsight Clinformatics Database, they identified 38,911,718 eligible patients who were commercially insured (median age, 31 years; 49.9% female). Of those, 45,341 developed CDI after a median follow-up of 1.9 years (median age, 46 years; 58.9% female), with 1,669 experiencing mrCDI.

Results indicated that between 2001 and 2012, there was a 42.7% increase (from 0.4408 to 0.6289 case) in the annual incidence of CDI per 1,000 person years and a 188.8% increase (from 0.0107 to 0.0309 case) in the annual incidence of mrCDI per 1,000 person-years. The extreme increase in mrCDI was independent of other known risk factors of CDI, apparent throughout the United States and dramatically exceeded the increased incidence of CDI. An increased risk for developing mrCDI was observed in older adults (median age, 56 vs. 49 years; adjusted OR per 10-year increase in age, 1.25 [95% CI, 1.21-1.29]), females (63.8% vs. 58.7%; aOR, 1.24 [95% CI, 1.11-1.38]) and those who used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [95% CI, 1.59-2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [95% CI, 1.01-1.29]) or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1-1.32]) within 90 days of CDI diagnosis. Further, those with chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [95% CI, 1.24-1.8]) and who were diagnosed in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [95% CI, 1.34-2.93]) were more likely to have mrCDI.

“These data project an increasing demand for therapies to treat mrCDI, which will likely translate into greater use of FMT in the coming years,” Ma and colleagues concluded. “Although FMT is highly effective and apparently safe in the short term, the results of this study highlight the importance of establishing the long-term safety of FMT given the projected increase in demand for this therapy. In addition, these findings reveal avenues of further study that may help guide the modification of treatment algorithms to reduce the incidence of mrCDI.”

In a related editorial, Sameer D. Saini, MD, MS, and Akbar K. Waljee, MD, MSc, both from the VA Ann Arbor Center for Clinical Management Research and the University of Michigan, wrote that the findings by Ma and colleagues is an important beginning to better understanding mrCDI, its scope, epidemiology and risk factors, as well as developing a comprehensive approach to address the growing public health challenge. – by Alaina Tedesco

Disclosure: Ma and colleagues report primary funding from National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases. Saini reports receiving personal fees from FMS Inc. and grants from Veterans Affairs Health Services Research and Development. Waljee reports receiving support by a Veterans Affairs Health Services Research and Development Career Development Award.

Between 2001 and 2011, the incidence of multiply recurrent Clostridium difficile infection increased significantly, which will likely increase the demand for therapies — such as fecal microbiota transplantation — to treat the condition, according to research published in Annals of Internal Medicine.

“Incidence of [Clostridium difficile] is widely believed to have increased over the past 2 decades, with hospitalizations for the infection in the United States doubling between 2000 and 2010,” Gene K. Ma, MD, from the University of Pennsylvania Perelman School of Medicine, and colleagues wrote. “However, little is known about trends in incidence of recurrent CDI, particularly [multiply recurrent CDI (mrCDI)], which would be an indication for [fecal microbiota transplantation (FMT)]. Knowledge of the magnitude of this problem and projection of the potential demands on the health care system in the coming years are needed.”

Ma and colleagues conducted a retrospective cohort study to investigate whether the occurrence of mrCDI is increasing in proportion to CDI, as well as to identify risk factors for mrCDI. Using the OptumInsight Clinformatics Database, they identified 38,911,718 eligible patients who were commercially insured (median age, 31 years; 49.9% female). Of those, 45,341 developed CDI after a median follow-up of 1.9 years (median age, 46 years; 58.9% female), with 1,669 experiencing mrCDI.

Results indicated that between 2001 and 2012, there was a 42.7% increase (from 0.4408 to 0.6289 case) in the annual incidence of CDI per 1,000 person years and a 188.8% increase (from 0.0107 to 0.0309 case) in the annual incidence of mrCDI per 1,000 person-years. The extreme increase in mrCDI was independent of other known risk factors of CDI, apparent throughout the United States and dramatically exceeded the increased incidence of CDI. An increased risk for developing mrCDI was observed in older adults (median age, 56 vs. 49 years; adjusted OR per 10-year increase in age, 1.25 [95% CI, 1.21-1.29]), females (63.8% vs. 58.7%; aOR, 1.24 [95% CI, 1.11-1.38]) and those who used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [95% CI, 1.59-2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [95% CI, 1.01-1.29]) or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1-1.32]) within 90 days of CDI diagnosis. Further, those with chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [95% CI, 1.24-1.8]) and who were diagnosed in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [95% CI, 1.34-2.93]) were more likely to have mrCDI.

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“These data project an increasing demand for therapies to treat mrCDI, which will likely translate into greater use of FMT in the coming years,” Ma and colleagues concluded. “Although FMT is highly effective and apparently safe in the short term, the results of this study highlight the importance of establishing the long-term safety of FMT given the projected increase in demand for this therapy. In addition, these findings reveal avenues of further study that may help guide the modification of treatment algorithms to reduce the incidence of mrCDI.”

In a related editorial, Sameer D. Saini, MD, MS, and Akbar K. Waljee, MD, MSc, both from the VA Ann Arbor Center for Clinical Management Research and the University of Michigan, wrote that the findings by Ma and colleagues is an important beginning to better understanding mrCDI, its scope, epidemiology and risk factors, as well as developing a comprehensive approach to address the growing public health challenge. – by Alaina Tedesco

Disclosure: Ma and colleagues report primary funding from National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases. Saini reports receiving personal fees from FMS Inc. and grants from Veterans Affairs Health Services Research and Development. Waljee reports receiving support by a Veterans Affairs Health Services Research and Development Career Development Award.

    Perspective
    Colleen R. Kelly

    Colleen R. Kelly

    This study by Ma and colleagues shows that the rates of mrCDI have greatly increased. Though the reasons for this are not entirely clear, perhaps increased virulence of the organism or decreased resilience of our collective gut microbiome, increasing vulnerability to recurrent infection, are to blame.  Importantly, they have identified a few modifiable risk factors for mrCDI, namely use of antibiotics and proton-pump inhibitors (PPI). Physicians should keep these risk factors in mind in treating patients with CDI. Antibiotic stewardship is important in everybody, but especially in patients who have suffered a recent CDI. Unfortunately, antibiotics are still frequently used unnecessarily, such as prophylactically before dental procedures in patients with prosthetic joints or to treat asymptomatic bacteriuria in the elderly. Physicians should carefully consider the risks vs. benefits of antibiotics in patients who have a recent history of CD and use narrow spectrum, lower risk antibiotics when possible. Similarly, PPIs are widely prescribed, often without an appropriate indication. An episode of CDI should prompt physicians to review the medication list, determine the reason that a patient is taking a PPI and discontinue this therapy if there is not a strong indication, such as reflux esophagitis or recent peptic ulcer. Patients with milder symptoms of gastroesophageal reflux disease may be changed to a Histamine H2-receptor antagonist instead. Finally, physicians may consider earlier use of alternative therapies, such as fidaxomicin, bezlotoxumab or FMT, in patients with multiple risk factors for mrCDI (e.g. elderly, female, chronic kidney disease, residing in nursing home).

    • Colleen R. Kelly, MD
    • Assistant Professor of Medicine The Alpert Medical School of Brown University Center for Women’s GI Medicine Providence, Rhode Island

    Disclosures: Kelly reports being a consultant for Summit Therapeutics and a site investigator for clinical trial (seres Heath).