Clostridium difficile infections in Finland, 2008-2015: trends, diagnostics and ribotypes.

We evaluated Clostridium difficile (CD) diagnostics in Finnish clinical microbiology laboratories during 2006-2011, with an update in 2015, in relation to CD surveillance data of the National Infectious Disease Register (NIDR) and ribotyping data from the national reference laboratory during the years 2008-2015. In 2011, diagnostic activity varied regionally more than three-fold and the positivity rate ranged between 7 and 21%. Nucleic acid amplification testing (NAAT) was implemented in the regions with high activity and NAAT users tested 30% more patients and found 15% more cases per population than those not using it. Culture was performed in 79% of laboratories, primary toxin testing by enzyme immunoassay (EIA) in 83% and by NAAT in 17%. In 2014, 12/19 laboratories used NAAT as the primary detection method and four as the secondary method, and ten cultured. Increasing usage of NAAT was not systematically related to various trends detected regionally in annual CD rates. Polymerase chain reaction (PCR) ribotyping of 1771 CD isolates (4.1% of CD cases) identified 146 distinct profiles, of which 37% were binary toxin positive. The most common ribotype was 027, but its proportion decreased, while 078 slightly increased. Transition from culture to NAAT in CD infection (CDI) diagnostics did not cause a significant increase in the observed CDI incidence. Major differences between diagnostic activity, methods and strategies in different regions have persisted over the years, which should be considered when comparing the regional epidemiology of CDI.

Incidence, case fatality and genotypes causing Clostridium difficile infections, Finland, 2008.

Since 2000, the epidemiology of C. difficile infections (CDI) has changed in the US and Europe. Few population-based assessments of both incidence and case fatality of CDI have been performed. In this study, the Finnish nationwide laboratory-based surveillance data from the year 2008 were analysed to assess the incidence and case fatality of CDI, and to detect regional differences in relation to molecular epidemiology. A total of 6201 episodes of CDI were identified (118.3/100 000 population; range by regions, 57.2-189.1). The incidence increased by age and was highest in persons aged >84 years (1286.0). Of the CDI episodes, 711 (11.5%; range by regions, 2.2-15.0%) led to death within 30 days. The 30-day case fatality was highest (22.0%) in persons aged >84 years. In total, 334 (5% of all episodes) isolates from 13/21 regions were sent for genotyping: 120 (36%) were of PCR ribotype 027, and it was found in 6/13 regions. Among the rest of the isolates, 53 (16%) were of type 001, and 19 (6%) of 002 and 014. The incidence and case fatality were highest in elderly persons and varied regionally. This may be explained by uneven spread of hypervirulent PCR ribotypes, such as 027, but also differences in diagnostic activity or the patient populations among which the outbreaks are occurring.

Comparison of repetitive extragenic palindromic sequence-based PCR with PCR ribotyping and pulsed-field gel electrophoresis in studying the clonality of Clostridium difficile.

Clostridium difficile infection is most often induced by antibiotic treatment. Recently, morbidity and mortality resulting especially from C. difficile PCR ribotype 027 have increased significantly. In addition, more severe disease has been associated with C. difficile PCR ribotype 078 strains. Thus, reliable typing methods for epidemic control are needed. In the present study, we compared an automated repetitive extragenic palindromic sequence-based PCR (rep-PCR) method (DiversiLab; Bacterial Barcodes, Inc., Athens, GA, USA) to PCR ribotyping and pulsed-field gel electrophoresis (PFGE) typing using 205 isolates of C. difficile (including 24 previously characterized isolates). Among the 181 clinical isolates, a total of 31 different PCR ribotypes, 38 different PFGE types and subtypes and 28 different rep-PCR types were found. Six major rep-PCR groups (DL1-DL6) harboured 86% of the clinical isolates. All isolates belonging to PCR ribotypes 027 and 001 clustered in their own rep-PCR groups, enabling us to screen out the hypervirulent ribotype 027 strain. Within the PCR ribotype 001, four subgroups were found using rep-PCR. Overall, in 75% (135/181) of the isolates, the classification attributed following rep-PCR and PCR ribotyping was comparable. In conclusion, the automated rep-PCR-based typing method represents an option for first-line molecular typing in local clinical microbiology laboratories. The method was easy to use as well as rapid, requiring less hands-on time than PCR ribotyping or PFGE typing. The conventional PCR ribotyping or PFGE, however, are needed for confirmatory molecular epidemiology. In addition, more epidemiology-oriented studies are needed to examine the discriminatory power of automated rep-PCR with isolates collected from a larger geographical area and during a longer period of time.

Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008.

Outbreaks of Clostridium difficile infections (CDI) with increased severity, high relapse rate and significant mortality have been related to the emergence of a new, hypervirulent C. difficile strain in North America and Europe. This emerging strain is referred to as PCR ribotype 027 (Type 027). Since 2005, individual countries have developed surveillance studies about the spread of type 027.C. difficile Type 027 has been reported in 16 European countries. It has been responsible for outbreaks in Belgium, Germany, Finland, France, Ireland, Luxembourg, The Netherlands, Switzerland and the United Kingdom (England, Wales, Northern Ireland and Scotland). It has also been detected in Austria, Denmark, Sweden, Norway, Hungary, Poland and Spain. Three countries experienced imported patients with CDI due to Type 027 who acquired the infection abroad.The antimicrobial resistance pattern is changing, and outbreaks due to clindamycin-resistant ermB positive Type 027 strains have occurred in three European countries. Ongoing epidemiological surveillance of cases of CDI, with periodic characterisation of the strains involved, is required to detect clustering of cases in time and space and to monitor the emergence of new, highly virulent clones.