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The epidemiology of Clostridium Difficile infections in kidney transplant recipients: an analysis of incidence, risk factors, management, prevention, prognostic determinants and outcomes Jia Qi Li1 Faculty of Arts and Science, University of Toronto
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Corresponding author: Jia Qi Li (lig@uhnresearch.ca)
Abstract
Kidney transplantation is the ideal treatment for end-stage renal disease. However, post-operative maintenance required to preserve the transplanted organ includes a lifetime of immunosuppression as well as frequent antibiotics, leaving kidney transplant recipients (KTRs) particularly vulnerable to infections. Clostridium difficile, a gram-positive bacterium, is one opportunistic infective agent that affects KTRs. C. difficile infections (CDIs) occur in the gut, where disruptions in the natural microbiome often caused by wide-spectrum antibiotics allow the species to expand and produce toxins, leading to significant diarrhea and colitis, and in some cases even toxic megacolon or death. Literature in the area of CDIs in the KTR population is sparse and plagued by inconsistencies and inadequacies in the diagnostic methods used. Due to this, the reported incidence rates vary between lower than 1% to as high as 8%. Common risk factors found included bacterial colonization, blood and human leukocyte antigen (HLA) incompatible transplants, antibiotic usage, and certain immunosuppressive medications such as anti-thymocyte globulins and mycophenolate mofetil. Management usually begins with withdrawal of any potentially causative antibiotics, and subsequent replacement with targeted antibiotics such as metronidazole and vancomycin – this approach was found to be effective in the KTR population, however prophylaxis was suggested as an area that needed more research. Relationships between CDIs and graft outcome have been poorly studied, with no reports CDIs leading to higher numbers of graft failure or rejection – this may suggest, at least in the short term, that CDI has little impact on graft outcome, however longer term studies are needed.
Introduction
Kidney transplantation is most often the desirable treatment for end-stage renal disease. It offers advantages such as improved quality of life and lower rates of mortality compared to other renal replacement therapies[1]. Despite these advantages, the postoperative maintenance required to maintain allograft function renders the kidney recipient population vulnerable to post-transplant infections. In particular, immunosuppression and antibiotic usage, both of which are ubiquitous in the kidney transplant population, are established risk factors for one possible infectious agent, Clostridium difficile [2,3]. Within the current literature, there is immense variability in the incidence and risk factors of C. difficile infections in kidney transplant recipients. The methods used to diagnose C. difficile vary, with the majority of studies using diagnostic methods that are considered suboptimal, especially within the context of epidemiological studies [4]. Although kidney transplant recipients appear to be at high risk, the epidemiology of C. difficile
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infections in this population has not been characterized well in the current literature.
Clostridium difficile
C. difficile is a Gram-positive bacterium that colonizes the human gastrointestinal tract [3]. It is transmitted via the fecaloral route, and is able to form spores that are capable of resisting harsher conditions than the bacterium itself. This makes it particularly amenable to transmission in a hospital setting [3]. Symptoms of the infection only occur if patients are colonized with sufficient amounts of toxicogenic strains of C. difficile which produce toxin A or B (tcdA/B) [3]. Even then, patients colonized with these strains may never become symptomatic as, under normal circumstances, any C. difficile proliferation is limited by competition with other microorganisms of the gut microbiota [3]. However, pharmaceuticals such as broad-spectrum antibiotics often disrupt this balance, facilitating the colonization and expansion of C. difficile into
Journal of Undergraduate Life Sciences • Volume 10 • Issue 1 • Spring 2016