Dataset Information

Clostridium difficile PCR Ribotype 018, a Successful Epidemic Genotype.

ABSTRACT: Clostridium difficile infection (CDI) became a public health problem for the global spreading of the so-called hypervirulent PCR ribotypes (RTs) 027 and 078, associated with increases in the transmission and severity of the disease. However, especially in Europe, several RTs are prevalent, and the concept of hypervirulence is currently debated. We investigated the toxin and resistance profiles and the genetic relatedness of 312 C. difficile strains isolated in a large Italian teaching hospital during a 5-year period. We evaluated the role of CDI-related antibiotic consumption and infection control practices on the RT predominance in association with their molecular features and transmission capacity. Excluding secondary cases due to nosocomial transmission, RT018 was the predominant genotype (42.4%) followed by RT078 (13.6%), while RT027 accounted for 0.8% of the strains. RT078 was most frequently isolated from patients in intensive care units. Its prevalence significantly increased over time, but its transmission capacity was very low. In contrast, RT018 was highly transmissible and accounted for 95.7% of the secondary cases. Patients with the RT018 genotype were significantly older than those with RT078 and other RTs, indicating an association between epidemic RT and age. We provide here the first epidemiological evidence to consider RT018 as a successful epidemic genotype that deserves more attention in clinical practice.

SUBMITTER: Baldan R

PROVIDER: S-EPMC4508423 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Clostridium difficile PCR Ribotype 018, a Successful Epidemic Genotype.

Baldan Rossella R Trovato Alberto A Bianchini Valentina V Biancardi Anna A Cichero Paola P Mazzotti Maria M Nizzero Paola P Moro Matteo M Ossi Cristina C Scarpellini Paolo P Cirillo Daniela Maria DM

Journal of clinical microbiology 20150603 8

Clostridium difficile infection (CDI) became a public health problem for the global spreading of the so-called hypervirulent PCR ribotypes (RTs) 027 and 078, associated with increases in the transmission and severity of the disease. However, especially in Europe, several RTs are prevalent, and the concept of hypervirulence is currently debated. We investigated the toxin and resistance profiles and the genetic relatedness of 312 C. difficile strains isolated in a large Italian teaching hospital d ...[more]

PMID: 26041894

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Project description:The increasing clinical importance of human infections (frequently severe) caused by Clostridium difficile PCR ribotype 078 (RT078) was first reported in 2008. The severity of symptoms (mortality of ?30%) and the higher proportion of infections among community and younger patients raised concerns. Farm animals, especially pigs, have been identified as RT078 reservoirs. We aimed to understand the recent changes in RT078 epidemiology by investigating a possible role for antimicrobial selection in its recent evolutionary history. Phylogenetic analysis of international RT078 genomes (isolates from 2006 to 2014, n?=?400), using time-scaled, recombination-corrected, maximum likelihood phylogenies, revealed several recent clonal expansions. A common ancestor of each expansion had independently acquired a different allele of the tetracycline resistance gene tetM Consequently, an unusually high proportion (76.5%) of RT078 genomes were tetM positive. Multiple additional tetracycline resistance determinants were also identified (including efflux pump tet40), frequently sharing a high level of nucleotide sequence identity (up to 100%) with sequences found in the pig pathogen Streptococcus suis and in other zoonotic pathogens such as Campylobacter jejuni and Campylobacter coli Each RT078 tetM clonal expansion lacked geographic structure, indicating rapid, recent international spread. Resistance determinants for C. difficile infection-triggering antimicrobials, including fluoroquinolones and clindamycin, were comparatively rare in RT078. Tetracyclines are used intensively in agriculture; this selective pressure, plus rapid, international spread via the food chain, may explain the increased RT078 prevalence in humans. Our work indicates that the use of antimicrobials outside the health care environment has selected for resistant organisms, and in the case of RT078, has contributed to the emergence of a human pathogen.IMPORTANCE Clostridium difficile PCR ribotype 078 (RT078) has multiple reservoirs; many are agricultural. Since 2005, this genotype has been increasingly associated with human infections in both clinical settings and the community. Investigations of RT078 whole-genome sequences revealed that tetracycline resistance had been acquired on multiple independent occasions. Phylogenetic analysis revealed a rapid, recent increase in numbers of closely related tetracycline-resistant RT078 (clonal expansions), suggesting that tetracycline selection has strongly influenced its recent evolutionary history. We demonstrate recent international spread of emergent, tetracycline-resistant RT078. A similar tetracycline-positive clonal expansion was also identified in unrelated nontoxigenic C. difficile, suggesting that this process may be widespread and may be independent of disease-causing ability. Resistance to typical C. difficile infection-associated antimicrobials (e.g., fluoroquinolones, clindamycin) occurred only sporadically within RT078. Selective pressure from tetracycline appears to be a key factor in the emergence of this human pathogen and the rapid international dissemination that followed, plausibly via the food chain.

Project description:BackgroundClostridium difficile infection (CDI) is an emerging healthcare problem in the world. The purpose of this study was to perform a systematic epidemiological research of CDI in Tongji hospital, the central of China.MethodsStool samples from hospitalized adults suspected of CDI were enrolled. The diagnosis of CDI were based on the combination of clinical symptoms and laboratory results. Clinical features of CDI and non-CDI patients were compared by appropriate statistical tests to determine the risk factors of CDI. Multilocus sequence typing (MLST) was employed for molecular epidemiological analysis. Susceptibility testing and relevant antimicrobial agent resistance genes were performed as well.ResultsFrom June 2016 to September 2017, 839 hospitalized adults were enrolled. Among them, 107 (12.8%, 107/839) patients were C. difficile culture positive, and 73 (8.7%, 73/839) were infected with toxigenic C. difficile (TCD), with tcdA + tcdB+ strains accounting for 90.4% (66/73) and tcdA-tcdB+ for 9.6% (7/73). Meanwhile, two TCD strains were binary toxin positive and one of them was finally identified as CD027. Severe symptoms were observed in these two cases. Multivariate analysis indicated antibiotic exposure (p = 0.001, OR = 5.035) and kidney disease (p = 0.015, OR = 8.329) significantly increased the risk of CDI. Phylogenetic tree analysis demonstrated 21 different STs, including one new ST (ST467); and the most dominant type was ST54 (35.6%, 26/73). Multidrug-resistant (MDR) TCD were 53.4% (39/73); resistance to ciprofloxacin, erythromycin, and clindamycin were > 50%. Other antibiotics showed relative efficiency and all strains were susceptible to metronidazole and vancomycin. All moxifloxacin-resistant isolates carried a mutation in GyrA (Thr82 → Ile), with one both having mutation in GyrB (Ser366 → Ala).ConclusionsKnowledge of epidemiological information for CDI is limited in China. Our finding indicated tcdA + tcdB+ C. difficile strains were the dominant for CDI in our hospital. Significant risk factors for CDI in our setting appeared to be antibiotic exposure and kidney disease. Metronidazole and vancomycin were still effective for CDI. Although no outbreak was observed, the first isolation of CD027 in center China implied the potential spread of this hypervirulent clone. Further studies are needed to enhance our understanding of the epidemiology of CDI in China.

Project description:Clostridium difficile is the main cause of antibiotic associated diarrhea. In the past decade, the number of C. difficile patients has increased dramatically, coinciding with the emergence of two PCR ribotypes 027 and 078. PCR ribotype 078 is also frequently found during C. difficile outbreaks in pigfarms. Previously, the genome of the PCR ribotype 078 strain M120, a human isolate, was described to contain a unique insert of 100 kilobases.Analysis of this insert revealed over 90 open reading frames, encoding proteins originating from transposons, phages and plasmids. The insert was shown to be a transposon (Tn6164), as evidenced by the presence of an excised and circularised molecule, containing the ligated 5'and 3'ends of the insert. Transfer of the element could not be shown through filter-mating experiments. Whole genome sequencing of PCR ribotype 078 strain 31618, isolated from a diarrheic piglet, showed that Tn6164 was not present in this strain. To test the prevalence of Tn6164, a collection of 231 Clostridium difficile PCR ribotype 078 isolates from human (n = 173) and porcine (n = 58) origin was tested for the presence of this element by PCR. The transposon was present in 9 human, tetracycline resistant isolates, originating from various countries in Europe, and none of the pig strains. Nine other strains, also tetracycline resistant human isolates, contained half of the transposon, suggesting multiple insertion steps yielding the full Tn6164. Other PCR ribotypes (n = 66) were all negative for the presence of the transposon. Multi locus variable tandem repeat analysis revealed genetic relatedness among transposon containing isolates. Although the element contained several potential antibiotic resistance genes, it did not yield a readily distinguishable phenotype.Tn6164 is a newly described transposon, occurring sporadically in C. difficile PCR ribotype 078 strains. Although no transfer of the element could be shown, we hypothesize that the element could serve as a reservoir of antibiotic resistance genes for other bacteria. Further research is needed to investigate the transfer capabilities of the element and to substantiate the possible role of Tn6164 as a source of antibiotic resistance genes for other gut pathogens.

Dataset Information

Clostridium difficile PCR Ribotype 018, a Successful Epidemic Genotype.

Publications

Clostridium difficile PCR Ribotype 018, a Successful Epidemic Genotype.

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