This study investigated the MICs of 17 antimicrobials, for 606 toxigenic clinical isolates of Clostridium difficile collected between 1993 and 2007 in Sweden. Low MIC90 values were found for ...metronidazole (0.5 mg/L), vancomycin (1.0 mg/L), teicoplanin (0.125 mg/L), fusidic acid (1.0 mg/L), linezolid (2.0 mg/L), daptomycin (2.0 mg/L) and tigecycline (0.064 mg/L). Three isolates (0.5%) had elevated MICs for vancomycin (4–8 mg/L); however, these isolates originated from the same patient, who was receiving long-term intravenous vancomycin treatment. High-level clindamycin resistant isolates (MIC >256 mg/L) peaked in 1997 with 39 of 95 (41%) and out of these, 36% were also highly resistant to erythromycin. β-Lactams such as penicillin V and piperacillin displayed MIC90s of 8 and 32 mg/L, respectively, whereas MICs of cefuroxime were >256 mg/L for all isolates. Universal resistance to ciprofloxacin and levofloxacin was found, and resistance to moxifloxacin increased from 4% of isolates in 2004 to 23% in 2007. Notably, these moxifloxacin-resistant isolates did not belong to the recent epidemic PCR ribotype 027, but to the pre-existing epidemic type 012 (82%), and these isolates accounted for the majority of isolates that were resistant to clindamycin (70%), tetracycline (84%) and rifampicin (92%) as well. This investigation of susceptibility data on clinical C. difficile isolates showed variations of multiresistance to be due to a specific PCR ribotype 012, emphasizing the importance of genotyping when evaluating emerging resistance over time.
Abstract An aggregation of moxifloxacin-resistant Clostridium difficile ribotype 231 (RT231) isolates was first identified in the county of Stockholm in 2008, and by the end of 2015 isolates of RT231 ...had spread to 13 of 21 Swedish counties. We investigated the epidemiology of C. difficile RT231 in Sweden between 2006 and 2015 using whole genome sequencing (WGS) and evaluated whether its emergence could be associated with extended moxifloxacin use. We performed WGS and phylogenetic analysis of 51 C. difficile RT231 strains isolated in Sweden over a 10-year period. We also calculated the county-specific prescription rates for moxifloxacin between 2005 and 2015. Using WGS and detailed single nucleotide polymorphism analysis, we demonstrated three divergent sublineages of moxifloxacin-resistant C. difficile RT231 in Sweden from 2008 to 2015. A set of closely related RT231 was identified in hospitals located in the counties of Stockholm and Uppsala in 2008. Another set of RT231 isolates was found in four different counties in the Uppsala–Örebro Health Care Region. A gradual drop in moxifloxacin use in the county of Stockholm coincided with a reduction of RT231 in the area. However, RT231 continued to be frequent in surrounding counties including Uppsala, a county that also had the highest moxifloxacin prescription rates. We demonstrated frequent transmission of C. difficile RT231 within and between counties, indicating the importance of careful monitoring of hospitalized individuals infected with moxifloxacin-resistant C. difficile as well as the need for a strict moxifloxacin prescription policy.
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.
In a 10-year period, 1987–1997, there was a >4-fold increase in the rate of pneumococcal bacteremia in Sweden. Invasive pneumococcal isolates (n=1136), which were obtained from 18 Swedish clinical ...microbiology laboratories from 1987 through 1997, and other national and international isolates were serotyped, and their clonal relationships were determined by molecular typing. The increase in invasive pneumococcal disease in Sweden during this period was associated particularly with an increase in isolates of serotypes 1 and 14. A 3-fold increase of type 14 was seen from 1987 through 1992, and a 10-fold increase of type 1 occurred from 1992 through 1997. One dominating penicillin-susceptible clone of type 14 was responsible for the increase of type 14 during the first 5 years. This clone also was found in Canada and the United States and was shown by multilocus sequence typing to correspond to a previously identified hyper-virulent clone. A novel penicillin-susceptible clone of type 1, which was not found among invasive isolates from 1987 or 1992, was responsible for the increase of serotype 1 during the last 5 years. These results illustrate the ability of virulent penicillin-susceptible pneumococcal clones to emerge and spread rapidly within a country
The increasing incidence of Clostridium difficile infections (CDI) in healthcare settings in Europe since 2003 has affected both patients and healthcare systems. The implementation of effective CDI ...surveillance is key to enable monitoring of the occurrence and spread of C. difficile in healthcare and the timely detection of outbreaks.
The aim of this review is to provide a summary of key components of effective CDI surveillance and to provide some practical recommendations. We also summarize the recent and current national CDI surveillance activities, to illustrate strengths and weaknesses of CDI surveillance in Europe.
For the definition of key components of CDI surveillance, we consulted the current European Society of Clinical Microbiology and Infectious Diseases (ESCMID) CDI-related guidance documents and the European Centre for Disease Prevention and Control (ECDC) protocol for CDI surveillance in acute care hospitals. To summarize the recent and current national CDI surveillance activities, we discussed international multicentre CDI surveillance studies performed in 2005–13. In 2017, we also performed a new survey of existing CDI surveillance systems in 33 European countries.
Key components for CDI surveillance are appropriate case definitions of CDI, standardized CDI diagnostics, agreement on CDI case origin definition, and the presentation of CDI rates with well-defined numerators and denominators. Incorporation of microbiological data is required to provide information on prevailing PCR ribotypes and antimicrobial susceptibility to first-line CDI treatment drugs. In 2017, 20 European countries had a national CDI surveillance system and 21 countries participated in ECDC-coordinated CDI surveillance. Since 2014, the number of centres with capacity for C. difficile typing has increased to 35 reference or central laboratories in 26 European countries.
Incidence rates of CDI, obtained from a standardized CDI surveillance system, can be used as an important quality indicator of healthcare at hospital as well as country level.
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We recently attempted to clarify an increased incidence of
Clostridium difficile-associated diarrhoea (CDAD) in our hospital by arbitrarily primed polymerase chain reaction (AP-PCR) typing of ...isolates from 147 consecutive patients collected during a 12 month period (Wullt et al.
J Hosp Infect 1999;
43:265–273). In the present study we compared the results based on previous AP-PCR data with those based on recent PCR ribotyping of the same isolates and re-analysis of a subset of isolates by AP-PCR typing. The pattern of PCR ribotypes was similar among inpatients and outpatients. A cluster of three closely related PCR ribotypes, related to those of the serogroup H and A8 type strains, dominated and comprised 31% of inpatient and 28% of outpatient
C. difficile isolates. The apparent nosocomial transmission rate among inpatients with CDAD was only 9% by AP-PCR typing compared with 18 or 36% by PCR ribotyping depending on the definition used (proportion of patients sharing
C. difficile type and ward within two or 12 months). Corresponding rates for all CDAD patients were 5% by AP-PCR and 11 or 21% by PCR ribotyping. Thus, most CDAD patients apparently became ill due to their endogenous strain of
C. difficile. Because of the low concordance between the two typing methods the proportion of patients fulfilling the criteria for nosocomial transmission by both methods was only 1%. Re-examination of isolates from patients with recurrences revealed a reproducibility problem with AP-PCR typing. We conclude, that of these two PCR-based options for typing of
C. difficile PCR ribotyping offers a superior experimental robustness compared with AP-PCR typing.
To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for ...all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol.
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