Clostridium difficile-Associated Diarrhea – Reemergence of a Serious Disease and Exploring New Predictors for Treatment Failure
Clostridium difficile-Associated Diarrhea (CDAD) or Clostridium difficile Infection (CDI) in the past 15 or so years has emerged as a serious challenge due to the following reasons:
[] Infections are more commonly seen, especially in older population. Nursing home and other assisted living residents with medical comorbidities are highly vulnerable to this potentially devastating illness.
[] Emergence and global spread of bacterial strains that frequently lead to serious diarrheal illness (hypervirulent strains) have become a commonplace occurrence.
[] The response to treatment is now less than satisfactory to medications that are regarded as standard-of-care, such as oral metronidazole and oral vancomycin.
[] Development of drug resistance among disease causing C. difficile bacteria DO NOT play a role in the noticeable less-than-satisfactory response to conventional drug therapy.
[] Infections recur (come back) after a course of successful therapy at an alarming rate and with each episode of C. diff returned infection, successful therapy becomes even more difficult to achieve.
[] Presently, arbitrary measures and indicators are used to predict response to anti-C. diff therapy, and to assess the risk for infection recurrence. Availability of reliable predictor(s) to evaluate such important parameters is highly desirable.
Khanna S, et al, recently published their finding regarding the aforementioned predictors of treatment response in patients with CDI and those individuals at risk for disease recurrence.
The authors postulated that individuals’ “microbial signature” which represents the bacterial flora in the intestinal tract may have an influencing on predicting response to CDI therapy.
Employing high-throughput nucleic acid sequencing analysis they were able to show that patient who had a response to CDI therapy, the risk-index was significantly favorable in the setting of a prominent presence of certain group of bacteria in the intestinal tract such as Ruminococcaceae, Rikenellaceae, Clostridiaceae, Bacteroides, Faecalibacterium and Rothia.
It was also interesting to note that patients who developed recurrent C. diff diarrhea had a different “microbial signature profile” (bacteria that normally reside in the gut). Probability of C. diff diarrhea recurrence (risk index) was significantly higher in patients with an increase intestinal presence of Veillonella, Enterobacteriaceae, Streptococci, Parabacteroides and Lachnospiraceae.
Please take note,
C. diff diarrhea has reemerged as a serious healthcare concern for patients in hospitals and older patients in the community and hospital alike.
Treatment response to CDI illness have declined over the past two decades. Newer treatment modalities are increasingly being sought to treat these difficult-to-treat infections.
More research is needed to validate “microbial signature profile” that may reliably predict and identify patients in whom, the risk for treatment failure is higher than general population. In concert, such profile analysis may also assist in recognizing individuals in advance, who may exhibit a higher probability of infection recurrence following initial successful anti-C. diff therapy.
Khanna S, Montassier E, Schmidt B, Patel R, Knights D, Pardi DS, Kashyap PC. Gut microbiome predictors of treatment response and recurrence in primary Clostridium difficile infection. Aliment Pharmacol Ther. 2016 Oct;44(7):715-27.
Siegfried J, Dubrovskaya Y, Flagiello T, Scipione M, Chen D, Phillips M, Papadopoulos J, Safdar A. Initial therapy for mild to moderate Clostridium difficile infection (CDI): exploring the role of oral metronidazole vs. vancomycin in 168 hospitalized patients. Infectious Diseases in Clinical Practice 2016;24:210-216.
Penziner S, Dubrovskaya Y, Press R, Safdar A. Fidaxomicin therapy in critically ill patients with Clostridium difficile infection. Antimicrob Agents Chemother. 2015 Mar;59(3):1776-81.
Clutter DS, Dubrovskaya Y, Merl MY, Teperman L, Press R, Safdar A. Fidaxomicin versus conventional antimicrobial therapy in 59 recipients of solid organ and hematopoietic stem cell transplantation with Clostridium difficile-associated diarrhea. Antimicrob Agents Chemother. 2013 Sep;57(9):4501-5.