The Epidemiology of Clostridium difficile Infection in Japan: A Systematic Review

Abstract

To increase understanding of the epidemiology, risks, consequences and resource utilization of Clostridium difficile infection (CDI) in Japan, a systematic literature review was undertaken of relevant publications from January 2006 to November 2017. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and methods, 55 articles met the criteria for full review. The majority (58%) of studies were from a single site, with the most recent data from 2015. The incidence, reported prevalence and recurrence rate of CDI in Japan were 0.8–4.71/10,000 patient-days, 0.3–5.5/1000 patients and 3.3–27.3%, respectively, and varied according to setting, population, CDI definition and detection method. Most C. difficile isolates associated with CDI in Japan were toxin A+B+, with a low level of C. difficile binary toxin-positive (CDT+) strains (0–6.8% reported across studies). The most common C. difficile PCR ribotypes associated with infection in Japan were smz/018, 002, 052 and 369. Data regarding the impact of CDI on length of hospital stay were limited. Reported all-cause mortality in patients with CDI ranged from 3.4 to 15.1% between 2007 and 2013. Two studies assessed risk factors for CDI recurrence, identifying malignant disease, intensive care unit hospitalization and use of proton pump inhibitors as factors increasing the risk of initial and/or recurrent CDI. No study analyzed initial CDI treatment in relation to recurrence. More comprehensive surveillance and coordinated studies are needed to map trends, understand risk factors, and recognize the extent and impact of CDI in Japanese patients.FundingAstellas Pharma, Inc.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s40121-018-0186-1) contains supplementary material, which is available to authorized users.

Molecular epidemiology of Clostridioides difficile and risk factors for the detection of toxin gene-positive strains

“…The most frequent ribotypes as revealed by PCR for toxin gene-positive strains were 047, 014/0, and 020 in this study. In a previous Japanese study, the ribotypes present at a high frequency were strains 018, 002, 052, and 369 [22]. In other Japanese study, the ribotypes present at a high frequency was strains 449 [17].…”

“…In other Japanese study, the ribotypes present at a high frequency was strains 449 [17]. The frequent PCR ribotypes varied by the studies in Japan [17,22]. In the United States, the most frequent PCR ribotypes were strains 002, 014e020, 027, and 053e163 [23], but the most frequent PCR ribotypes were different according to area.…”

Clostridioides (Clostridium) difficile infection in Japanese hospitals 2008–2017: A real-world nationwide analysis of treatment pattern, incidence and testing density

“…The CDI strain associated with more severe disease, ribotype 027, is rarely identified in Japan, which may help explain the widespread use of MNZ observed in our study [11,28]. Other reasons may include the less user-friendly formulation of oral VCM (supplied as powder in a vial) and the attempt to avoid potential VCM resistance.…”

“…A systematic review of published data from 2006 to 2017 found several evidence gaps including information on the treatments used for CDI (for example type, dose and duration) [11]. Most studies investigating CDI treatment in Japan have been conducted at single centers [12e15] or a limited number of hospitals [16,17], providing snapshots of CDI in certain patient subgroups rather than comprehensive reporting of trends in hospital-onset CDI over time.…”

Incidence and risk factors of a severe Clostridium difficile infection: results of a retrospective cohort study at a tertiary care hospital

“…CD spores can persist in the environment for extreme long time periods and, thus, facilitate nosocomial transmission and outbreaks [5] [6]. Unfortunately, CDIs have become an increasing clinical and financial burden in healthcare settings all over the world [7][8] [9]. Especially severe CDI courses contribute significantly to the morbidity and mortality of affected patients.…”