Prevalent C. difficile ribotypes in Asia
Ribotyping data with internationally recognised nomenclature are available for China, Japan, Singapore, Hong Kong, Taiwan, and Korea. Overall, the most prevalent ribotypes in Asia appear to be 017, 018, 014, 002, and 001. While ribotypes 027 and 078 have caused outbreaks in North America and Europe, they are reported only to have caused sporadic cases of CDI in Asia so far, in Singapore, Hong Kong, Korea, and Japan [
16,
34,
40,
46,
49,
63,
74]. Ribotype 078 has only been reported from Korea and China to date [
31,
37]. Another binary toxin-positive strain, ribotype 130, was recently reported from Korea [
19].
Meanwhile, ribotype 017, A
-B
+, toxinotype VIII strains are widespread in Asia, and have caused epidemics worldwide (Figure
1). In China and Korea 017 is the most common ribotype in circulation, and is prevalent in Japan, Taiwan, and Hong Kong also [
31,
32,
36,
39]. Exposure to antineoplastic agents, use of nasal feeding tubes, and care in a particular hospital ward were associated with infection with 017 strains in one hospital in Japan [
11]. Ribotype 017 strains have persisted in China and Taiwan while they appear to have declined in Korea (Figure
1).
In Japan, smz/018 appears to have persisted as the most common ribotype for over a decade (Figure
1). Ribotype smz/018 was the most prevalent strain isolated in a tertiary hospital in Seoul between September 2008 and January 2010 [
33], indicating spread from Japan to Korea. Ribotype 018 caused outbreaks of CDI in Italy in 2007/2008 and is the fourth most prevalent ribotype in Europe at present [
20,
21]. It is not clear whether smz/018 is prevalent in other Asian countries, as comparative typing with a reference smz or 018 strain may not have been performed.
Ribotypes 017 and 018 have caused widespread disease in Asia and across the world. Unlike the other major epidemic strains 027 and 078, they do not produce binary toxin, and ribotype 018 does not appear to possess variant toxin genes [
21]. Some other virulence factors may contribute to their spread. The resistance of ribotype 018 isolates to clindamycin and fluoroquinolones could contribute to their enhanced virulence [
8,
33,
40]. Another virulence factor is high sporulation rate. The epidemic ribotype 002 isolates in Hong Kong sporulated at a higher rate than other isolates, allowing them to persist in the hospital environment and cause outbreaks of disease [
40].
Prevention and control
Two reports of infection control in Asian hospitals were found. A hospital in India introduced control measures including disinfection of surfaces, rapid detection of
C. difficile by toxin assays, isolation of patients, controls on prescription of antibiotics and education of staff members. The incidence of CDI (initially 15% among cases of nosocomial diarrhoea) was reduced by 50% while the number of tests requested increased as health workers became more aware of CDI [
67]. A hospital-wide computerised antimicrobial stewardship scheme was introduced in a hospital in Taiwan. While the incidence of some antibiotic resistant organisms decreased, the isolation rate of
C. difficile remained constant at 10% [
44], indicating that other infection control measures besides antimicrobial stewardship would be required to control CDI in hospitals.
Asia is going through a period of rapid demographic change. With its dense, growing population, infection control is a pertinent issue. As C. difficile now causes the majority of nosocomial disease in North America and Europe, control measures could be applied in Asia to prevent the same situation there. A number of issues exist which could contribute to the spread of CDI in Asia.
As wealth and the aged population are increasing, more people have access to hospital care and enter aged care facilities. It is likely that CDI incidence could increase as these high-risk populations increase in size. For example, modelling of the future age structure of the Chinese population suggests that there will be a larger population at risk for CDI. Using census data from 2005 (population 1.3 billion) when only 100 million individuals were ≥65 years old, by 2026 there will be 200 million individuals ≥65 years [
75].
Antibiotic use in most Asian countries is poorly regulated. A review of Southeast Asian countries found that 47% of pneumonia cases do not receive an appropriate antibiotic, 54% of diarrhoea cases are unnecessarily treated with antibiotics, and 40% of antibiotics are prescribed in under-dose [
76]. In many cases inappropriate antibiotics are prescribed without any laboratory test. Studies in India have found the most commonly prescribed antibiotics for cough and respiratory disease are fluoroquinolones, a known risk factor for CDI [
76]. In addition, antibiotics are freely available without prescription in most Asian countries, leading to misuse in the community.
Given the free use of antibiotics by the general public it would be plausible that CA-CDI could be common in Asia. Studies in Asian countries have neglected to address the issue of CA-CDI, apart from two studies in Korea which found conflicting proportions of 7% and 59% of all CDI surveyed being community-acquired. It would be appropriate to monitor CA-CDI more closely in Asia in the future.
Despite widespread antibiotic use few studies in Asia have measured antimicrobial susceptibility of clinical
C. difficile isolates. High resistance rates to moxifloxacin, and clindamycin have been found in isolates from Korea, Japan, Northern Taiwan and China (Table
1). Heteroresistance to metronidazole has been reported from China, warranting close monitoring (Table
1).
Table 1
Antimicrobial resistance rates and MIC values for
Clostridium difficile
isolates from different countries
China
| | | | | | | | | |
| 75 | [76], 128, 128 | [66.7], 128, 128 | [41.3], 4, 64 | [45.3], 4, 128 | [100], 64, 128 | [0], <16/4, 16/4 | [0], 0.25, 0.25 | [0], 1, 2 |
| 110 | [85.3], 128, 128 | [88.1], 128, 128 | [62.7], 16, 32 | [61.8], 16, 128 | [100], 64, 128 | [0], 8/4, 16/4 | [0]a, 0.125, 0.25 | [0], 0.5, 1 |
Hong Kong
| | | | | | | | | |
| 35 | | | | | [100] | | 0.5, 0.75 | 0.75, 1.5 |
Japan
| | | | | | | | | |
| 73 | [87.7], >256, >256 | [87.7], >256, >256 | | | [100], >32, >32 | | [0], 0.19, 0.25 | [0], 2, 4 |
| 72 | | | | [12]b | [100] | | [0] | [0] |
Korea
| | | | | | | | | |
| 120 | | [50], 128, >128 | | [42], 2, 16 | | [0], 8, 16 | [0], 1,4 | [0], 0.5, 1 |
| 111 | | [82] | | [83] | | | | |
| 131 | | [67.9] | | [82] | | | [0] | [0] |
| 123 | | [75] | | [85] | | | | |
Singapore
| | | | | | | | | |
| 68 | | [63], 8, >512 | | | | | [0], 0.5, 1 | [0], 1, 1 |
Taiwan
| | | | | | | | | |
| 60 | | [73.3], 16, 64 | [41.7], 8, >16 | [30] | [100] | | | |
| 113 | | [46], 4, >256 | | [16] | | | [0] | |
Production and consumption of meat products is also increasing in Asia [
80]. Intensive farming of poultry, seafood and swine is already in place, and increasing with worldwide demand [
81]. The risk of
C. difficile colonisation and/or infection in animals would most likely increase with intensive farming practices including crowding of animals and prophylactic antibiotic use. Thus contamination of food products and animal-human transmission could occur. To date, no reports have been made of
C. difficile in the environment or animals, apart from five cases of fulminant colitis caused by ribotype 078 in thoroughbred racehorses in Japan [
82], and the isolation of
C. difficile from 2/ 250 (0.8%) swine faecal samples from 25 pig farms, also in Japan [
83].