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Eighth Annual Report of the National Reference Laboratory for Clostridium difficile and results of the sentinel surveillance

As of 2005, outbreaks with “hypervirulent” Clostridium difficile PCR ribotype 027 were recognized in the Netherlands. Soon after their recognition, the Center for Infectious Disease Control (CIb) of the National Institute for Public Health and the Environment (RIVM) started a typing service for C. difficile at the Leiden University Medical Center (LUMC). This “ad hoc typing” service was offered to all microbiological laboratories in the Netherlands, and medical microbiologists were requested to send C. difficile samples from patients with severe C. difficile infection (CDI) and from outbreaks to the Reference Laboratory.

As of May 2009, a sentinel surveillance was added with continuous monitoring of CDI in approximately 20 hospitals, including collection a minimum of clinical and epidemiological data and ribotyping of C. difficile isolates at the LUMC. Surveillance resulted in recognition of new emerging C. difficile PCR ribotypes, such as ribotype 078, which was also increasingly found in other European countries. In England, the prevalence of ribotype 078 has increased from 2% to 5% from 2007-2008 to 2009-2010, occurring during a remarkable decrease of the prevalence of ribotype 027.1 Ribotype 078 emerged to one of the three most frequently found ribotypes in Scotland between 2009-2013 (prevalence in 2013 of 6%).2

The Reference Laboratory is now able to recognize 174 PCR ribotypes. In the previous year, eleven new PCR ribotypes were added to the Reference Laboratory library.

Results of the sentinel surveillance

The results of the sentinel surveillance in the period May 2013-May 2014 in 20 hospitals showed that the mean incidence of CDI was 16.2 per 10.000 hospital admissions, varying from 4 to 30 per 10.000 admissions. No outbreaks were reported by surveillance hospitals. The most frequent encountered PCR ribotypes included ribotype 014/020 (n=147/1014; 14.5%), the closely related ribotypes 078 and 126 (n=136/1014; 13.4%), and ribotype 001 (n=84/1014; 8.3%). Compared to the previous years, the proportion of ribotype 001 continued to decrease (2010-2011 20%, n=187, 2011-2012 17%, n=138, 2012-2013 14%, n=131). The proportion of ribotype 002 (n=73/1014; 7.2%) was slightly higher than last year (n= 50; 6%). Proportions of ribotype 005, ribotype 014/020, ribotype 027, and ribotypes 078/126 were similar to last year. No important new or emerging ribotypes were observed.
For 693 out of 811 patients included in the surveillance the disease severity was reported; 21% had severe CDI. After 30 days, the outcome was reported for 635 patients; 2% of the patients (n=15) were admitted to the ICU and 11% died (n=70), of which 18 patients known to be contributable to CDI.

Results of ad hoc typing

In the period between May 1st 2013 and May 1st 2014, 18 facilities sent n=174 strains to the Reference Laboratory for ad hoc typing, because of outbreaks or severe cases of CDI. Ribotype 027 was the predominant ribotype, found in 31.7%, followed by ribotype 078/126 (11.2%). Seven outbreaks were reported; five of these outbreaks were caused by ribotype 027 and two by ribotype 001. Two hospitals needed extensive infection control measures, including antibiotic stewardship with restriction of fluoroquinolone use, to control 027 outbreaks. The 027 outbreak strain from one of these hospitals seems to have transmitted to at least seven other hospitals and seven nursing homes, using MLVA.

Burden of CDI in the Netherlands

Extrapolating the data of sentinel surveillance to all hospitals in the Netherlands, it is estimated that more than 3000 hospitalized patients annually will develop CDI. We estimated that 120 patients succumb contributable to CDI annually. In these estimations, the impact of CDI in other healthcare facilities than hospitals was not included.

By “ad hoc typing” it was observed that ribotype 027 re-emerged in several Dutch healthcare facilities and caused five outbreaks in the last year. Since the Reference Laboratory confirmed ninety cases and another seventy cases were typed locally, we estimate a burden of at least 160 patients affected by ribotype 027 in May 2013- May 2014. MLVA showed transmission of an 027 subtype between several healthcare facilities, in different regions of the Netherlands. Therefore, alertness for a re-emergence of ribotype 027 is warranted.

Wilcox et al. Changing epidemiology of Clostridium difficile infection following the introduction of a national ribotyping-based surveillance scheme in England. Clin Infect Dis. (2012) 55 (8): 1056-1063. doi: 10.1093/cid/cis614
2 Wiuff et al. Changing epidemiology of Clostridium difficile ribotypes in Scotland between 2009-2013 O005, ECCMID Barcelona 2014.

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