IASR

ISSN 0915-5813

Vol. 41 No. 3 (No. 481) March 2020
Infectious Agents Surveillance Reporthttps://www.niid.go.jp/niid/en/iasr-e.html

Fatal fulminant Clostridioides difficile colitis caused by Helicobacter
pylori eradication therapy, a case report............................................. 37
An outbreak of Clostridioides difficile including two cases withsevere complications, Kanagawa Prefecture, 2014.............................. 38
Clostridium difficile surveillance in England (translation: IASR Vol.41:
March, 2020).......................................................................................... 39
Intervention in an outbreak of Clostridioides difficile by the publichealth center of Koshigaya City, Saitama Prefecture, 2015............... 41
Clostridioides difficile infection in horses............................................... 42
Laboratory tests for the diagnosis of Clostridioides difficile infection.... 44

National Institute of Infectious Diseases andTuberculosis and Infectious Diseases
Control Division,Ministry of Health, Labour and Welfare

Treatments of Clostridioides difficile infection including fecal
microbiota transplantation (FMT)....................................................... 46
Challenges in measures against Clostridioides difficile infection
from the perspective of public health centers...................................... 47
Descriptive epidemiology of 12 confirmed cases of COVID-19
reported in Japan (as of February 3, 2020).......................................... 48
Chikungunya fever cases laboratory-diagnosed in 2016 and 2019,
Aichi Prefecture..................................................................................... 49
AH3 influenza virus classified as clade 3C.3a isolated in Aichi
Prefecture during the 2018/19 season................................................. 51<THE TOPIC OF THIS MONTH>
Clostridioides difficile infection in Japan
Clostridioides difficile infection (CDI)
Clostridioides (Clostridium) difficile is an obligate anaerobic Gram-positive spore-forming bacillus. Toxins produced by theorganism include toxin A, toxin B, and binary toxin.
C. difficile infection (CDI) is an intestinal infection that often develops when the disruption of the gut microbiota occurs(dysbiosis) by the use of antimicrobial agents. Host factors, such as advanced age and underlying disease, influence the onset of thedisease, and CDI is more common in the elderly. The symptoms range from mild diarrhea to toxic megacolon and ileus, and it may
be fatal in some cases (see pp. 37 and 38 of this issue). CDI is diagnosed when pseudomembranes are observed by colonic endoscopy,
but there are many cases of CDI without pseudomembrane formation. CDI often recurs and patients with multiple recurrences
present a difficult challenge for retreatment. On the other hand, inpatients, in particular, are often asymptomatically colonized byC. difficile. Patients without intestinal symptoms do not require testing or treatment.
Epidemiology of CDI
In North America and Europe, CDI is of great concern, and surveillance and infection control for CDI are being conductednationally. In “Antibiotic resistance threats in the United States 2019”, which was issued by the Centers for Disease Control andPrevention, C. difficile is listed as one of five pathogens that are an “urgent threat”, and infection control for CDI is performed underpolitical leadership in the US (https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf). In the UK,
from 2007 every hospital was mandated to report all of the cases of CDI, and the increased awareness of CDI led to its decreased
incidence (see p. 39 of this issue). In contrast, in Japan, the awareness of CDI is low, and infection control against CDI not only inhealthcare settings, but also in administrative settings is significantly behind that in North America and Europe. Although theincidence of CDI has been reported to be low in Japan, a recent multicenter prospective study revealed that the overall CDI
incidence in 12 hospitals was 7.4/10,000 patient-days, which is as high as those in North America and Europe. As CDI is rarely
suspected in outpatients with diarrhea (see p. 37 of this issue), the actual status of community-acquired CDI in Japan is unknown.
From a molecular epidemiological point of view, CDI due to PCR-ribotype (RT) 027 (BI/NAP1/027) has been repeatedly reporteda) 1996-1999

RT0176%c) 2011-2013b) 2003-2007
Other
types
21%

Other
types
18%

N=87

RT018
59%

RT002
10%

RT018
39%

RT369
11%

N=87

RT018
59%

RT017
1%
RT002
3%

RT014
7%

Other
types
21%

RT014
5%

N=120

RT369
16%

RT002
13%

RT014
11%d) 2014-2015
Other
types
24%

RT018
29%

N=146
RT369
11%
RT017
2%
RT002
12%a) between 1996 and 1999 at three hospitals(Kato H et al. J Clin Microbiol 2001)b) between 2003 and 2007 at four hospitals(Kato H et al. J Med Microbiol 2010)c) between 2011 and 2013 at 15 hospitals(Senoh M et al. J Med Microbiol 2015)d) between 2014 and 2015 at 12 hospitals(Kato H et al. Anaerobe 2019)

RT014
23%

Figure. Distribution of PCR-ribotypes in clinical isolates of Clostridioides difficile in Japan
PCR-ribotype (RT) 018 and its subtypes, 014 and 002 were toxin A-positive, toxin B-positive, binary toxin-negative; RT017 and RT369
were toxin A-negative, toxin B-positive, binary toxin-negative. Binary toxin-positive isolates were included in other types (RT027 C. difficile
was found in one patient in each of studies b) and c)).

1′（ 35′）（Continued on page 36′）IASR Vol. 41 No. 3（Mar. 2020） 2′（ 36′）（THE TOPIC OF THIS MONTH-Continued）
from North America and some European countries since 2004, attracting worldwide attention. It is known that the RT027 strain
emerged in North America and rapidly spread to Europe after acquiring resistance to fluoroquinolones. In Japan, in a 2007
administrative contact entitled “Thorough measures against nosocomial infections caused by Clostridium difficile or multidrugresistant Pseudomonas aeruginosa (MDRP)”, the Ministry of Health, Labour and Welfare notified thorough measures against
nosocomial infection by C. difficile, including infection by the RT027 strain. However, isolation of RT027 is currently rare in Japan(Figure in p. 35).
Among the Japanese isolates, RT018, RT014, RT002, RT369, and RT017 account for more than 75%. The most dominant types
are RT018 and its subtypes, and RT018 predominance has been recognized since the 1990s (Figure in p. 35). RT018 isolates arehighly resistant to antimicrobials, such as fluoroquinolones and clindamycin, and the selective pressure of antimicrobials usedconventionally, is presumed to be one of the factors for the predominance of this strain. The RT018 strain is also prevalent in Italy
and Korea, and the association between RT018 infection and disease severity was reported. In Japanese hospitals, CDI cases dueto RT018 often cluster and RT018 is an important epidemic strain causing nosocomial outbreaks (see p. 41 of this issue). The
RT002 strain has been associated with severe disease in Hong Kong, and serious cases and outbreaks have also been observed inJapan (see pp. 37 and 38 of this issue); it is considered to be a strain that should be paid attention to.
CDI in the veterinary field and one-health
It is relatively recent that studies on CDI in the veterinary field have become full-scale from the perspective of one-health (seep. 42 of this issue), whereas CDI in industrial animals and pets has been examined previously. Although there have been no reportsof food poisoning to date, attention has been paid for CDI and intestinal colonization by C. difficile in animals in relation to foodcontamination.
Diagnosis of CDI
A recent multicenter prospective study demonstrated the correlation between CDI test frequency and CDI incidence rate inpatients with diarrhea/colitis, revealing the importance of laboratory testing in patients with diarrhea/colitis to diagnose CDI.
Laboratory tests include enzyme immunoassay (EIA) detecting toxins (toxin A/toxin B) and glutamate-dehydrogenase (GDH) instool specimens, C. difficile culture, nucleic acid amplification test (NAAT) detecting the toxin B gene (tcdB) in stool specimens, andNAAT, which detects the binary toxin gene and presumptive RT027 C. difficile, in addition to tcdB. However, there is no omnipotent
test for diagnosing CDI. It is necessary to perform multiple tests under appropriate diagnostic stewardship and make a diagnosis
in combination with clinical symptoms (see p. 44 of this issue).
Treatment of CDI
Antimicrobial agents, if inciting dysbiosis, should be discontinued or changed. Antimicrobials for CDI include metronidazole,vancomycin, and fidaxomicin. Use of human monoclonal antibody against C. difficile toxin B, and fecal microbiota transplantation(as a clinical study in Japan), have been introduced as new treatments for repeated recurrences (see p. 46 of this issue). For
fulminant CDI cases that do not respond to medical treatment, emergency surgery is necessary. Total colectomy or subtotal
colectomy is performed, but diverting loop ileostomy may also be used to preserve the colon. Probiotics do not have therapeutic
efficacy against CDI.
Prevention of CDI
Implementation of antibiotic stewardship program and discontinuation of unneeded antacids are effective to reduce the riskof CDI.
For infection control of CDI, it should be noted that disinfectants commonly used for hand hygiene, such as alcohol, areineffective against C. difficile spores, and that asymptomatic carriers exist among hospitalized patients. When the prevalence ishigh, hand hygiene with running water and soap is essential. CDI patients should be placed on contact precautions. As asymptomaticcarriers can also be a source of infection, it is important to ensure that all inpatients are placed on thorough standard precautions,particularly in excretion assistance.
CDI is a disease that occurs, especially in healthcare facilities and wards where many elderly patients and patients requiring
antibiotic treatment are hospitalized. When the number of new disease cases exceeds that of normal levels, the situation isdescribed as an outbreak. Once a CDI outbreak occurs, it is markedly difficult to control (see pp. 38 and 41 of this issue). To detectsigns of outbreaks and provide a guide for the appropriate use of antibiotics, it is important to keep track of the baseline of CDI
incidence and frequency of laboratory testing at all times.
As elderly patients are often transferred between multiple hospitals and institutions, CDI is an infectious disease for which
infection control in the community should be considered. In particular, at many small- and medium-sized hospitals that have notearned additional reimbursement for infection prevention, more attention should be paid to CDI because the elderly account for themajority of patients, and infection control measures, including laboratory testing systems, are insufficient. The role of local
governments, including health centers, in the control of CDI infection will become even more important in the future (see pp. 41 and47 of this issue).
Next agenda
In Japan, the biggest problem in CDI control and prevention is the low awareness and understanding of CDI. It is necessary
to share correct information not only with medical institutions, but also with organizations related to health and hygiene such as
facilities for the elderly and local governments.
The statistics in this report are based on 1) the data concerning patients and laboratory findings obtained by the National Epidemiological
Surveillance of Infectious Diseases undertaken in compliance with the Act on the Prevention of Infectious Diseases and Medical Care for Patientswith Infectious Diseases, and 2) other data covering various aspects of infectious diseases. The prefectural and municipal health centers andpublic health institutes (PHIs), the Department of Environmental Health and Food Safety, the Ministry of Health, Labour and Welfare, andquarantine stations, have provided the above data.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases
Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, JAPAN Tel (+81-3)5285-1111