Clostridium difficile strain RT244 – Australia researchers

Researchers from Monash University in Australia have found that the RT244 Clostridium difficile strain, which was associated with severe disease and a high mortality rate, has significant pathogenic potential.

While there have been three separate known introductions of RT 027 into Australia in 2008 and two in 2010, the strain has not established here, possibly because of Australia’s conservative policies regarding fluoroquinolones. Nevertheless, there has been a significant increase in the rate of CDI in Australia over the past 3–4 years. Surveillance of hospital-identified (HI) CDI was mandated for public healthcare facilities in Western Australia in January 2010. The quarterly aggregate rate climbed from 1.47 per 10,000 bed days in the first quarter of 2010 to 2.64 per 10,000 bed days in the fourth quarter of 2010 and 4.59 per 10,000 bed days a year later, falling slightly to 4.27 per 10,000 bed days in the fourth quarter of 2012. Rates were approximately 1–3 times higher for tertiary hospitals alone3,4. In a laboratory-based, retrospective review of all cases of CDI identified in four acute care public hospitals in Tasmania between July 2006 and June 2010 inclusive, the annual rate increased from 2.5 per 10,000 patient-care days in 2006–07 to 4.2 per 10,000 patient-care days in 2009–105. The first report from Victoria following the commencement of targeted surveillance for CDI in 2010 was for the period October 2010 to March 2011 inclusive6. They reported a monthly increase in the number of HI-CDI cases, falling only in December 2010, and an overall rate of 2.2 per 10,000 occupied bed days. – See more at: http://microbiology.publish.csiro.au/?paper=MA14008#sthash.RVdbbLhF.dpuf
While there have been three separate known introductions of RT 027 into Australia in 2008 and two in 2010, the strain has not established here, possibly because of Australia’s conservative policies regarding fluoroquinolones. Nevertheless, there has been a significant increase in the rate of CDI in Australia over the past 3–4 years. Surveillance of hospital-identified (HI) CDI was mandated for public healthcare facilities in Western Australia in January 2010. The quarterly aggregate rate climbed from 1.47 per 10,000 bed days in the first quarter of 2010 to 2.64 per 10,000 bed days in the fourth quarter of 2010 and 4.59 per 10,000 bed days a year later, falling slightly to 4.27 per 10,000 bed days in the fourth quarter of 2012. Rates were approximately 1–3 times higher for tertiary hospitals alone3,4. In a laboratory-based, retrospective review of all cases of CDI identified in four acute care public hospitals in Tasmania between July 2006 and June 2010 inclusive, the annual rate increased from 2.5 per 10,000 patient-care days in 2006–07 to 4.2 per 10,000 patient-care days in 2009–105. The first report from Victoria following the commencement of targeted surveillance for CDI in 2010 was for the period October 2010 to March 2011 inclusive6. They reported a monthly increase in the number of HI-CDI cases, falling only in December 2010, and an overall rate of 2.2 per 10,000 occupied bed days. – See more at: http://microbiology.publish.csiro.au/?paper=MA14008#sthash.RVdbbLhF.dpuf

They conducted a retrospective cohort study that included 12 patients with the RT244 strain and 24 matched patients with a non-RT244/non-RT027 strain. They performed whole-genome sequencing on the strains to understand how the RT244 strain was related to other strains. There was no difference in age or comorbidities between the two groups and most patients had antibiotic exposure.

* While there have been three separate known introductions of RT 027 into Australia in 2008 and two in 2010, the strain has not established here, possibly because of Australia’s conservative policies regarding fluoroquinolones. Nevertheless, there has been a significant increase in the rate of CDI in Australia over the past 3–4 years. Surveillance of hospital-identified (HI) CDI was mandated for public healthcare facilities in Western Australia in January 2010. The quarterly aggregate rate climbed from 1.47 per 10,000 bed days in the first quarter of 2010 to 2.64 per 10,000 bed days in the fourth quarter of 2010 and 4.59 per 10,000 bed days a year later, falling slightly to 4.27 per 10,000 bed days in the fourth quarter of 2012. Rates were approximately 1–3 times higher for tertiary hospitals alone3,4. In a laboratory-based, retrospective review of all cases of CDI identified in four acute care public hospitals in Tasmania between July 2006 and June 2010 inclusive, the annual rate increased from 2.5 per 10,000 patient-care days in 2006–07 to 4.2 per 10,000 patient-care days in 2009–105. The first report from Victoria following the commencement of targeted surveillance for CDI in 2010 was for the period October 2010 to March 2011 inclusive6. They reported a monthly increase in the number of HI-CDI cases, falling only in December 2010, and an overall rate of 2.2 per 10,000 occupied bed days.

Another potential explanation for the increase in CDI rates is the emergence of new strains. RT 244 was first identified in Australia in 2011 and preliminary data suggested it was associated with more severe disease. This was recently supported by De Almeida et al.12 who, after identifying a new strain in New Zealand as RT 244, performed a case-control study of cases with CDI due to this RT. Cases had more severe disease (OR 9.33; P = 0.015) and were more likely to have community-associated infections (prevalence ratio 3.33; P = 0.078) when compared with controls who were infected with other C. difficile strains. Like RT 027, RT 244 produces more toxins A and B as a result of a single base pair deletion in tcdC (a gene involved in regulation of toxin A and B production), as well as binary toxin. RT 244 is therefore identified as a putative RT 027 with the Cepheid Xpert® C. difficile/Epi system. Other emerging RTs in Australia include RT 251 (A+B+CDT+), which also appears to be closely related to RT 027, and RT 033 (ABCDT+), RT 126 (A+B+CDT+) and RT 127 (A+B+CDT+), which are closely related to RT 078 (A+B+CDT+), a RT originally only isolated from animals, particularly livestock, in the Northern hemisphere and also associated with more severe disease – See more at: http://microbiology.publish.csiro.au/?paper=MA14008#sthash.RVdbbLhF.dpuf
Another potential explanation for the increase in CDI rates is the emergence of new strains. RT 244 was first identified in Australia in 2011 and preliminary data suggested it was associated with more severe disease. This was recently supported by De Almeida et al.12 who, after identifying a new strain in New Zealand as RT 244, performed a case-control study of cases with CDI due to this RT. Cases had more severe disease (OR 9.33; P = 0.015) and were more likely to have community-associated infections (prevalence ratio 3.33; P = 0.078) when compared with controls who were infected with other C. difficile strains. Like RT 027, RT 244 produces more toxins A and B as a result of a single base pair deletion in tcdC (a gene involved in regulation of toxin A and B production), as well as binary toxin. RT 244 is therefore identified as a putative RT 027 with the Cepheid Xpert® C. difficile/Epi system. Other emerging RTs in Australia include RT 251 (A+B+CDT+), which also appears to be closely related to RT 027, and RT 033 (ABCDT+), RT 126 (A+B+CDT+) and RT 127 (A+B+CDT+), which are closely related to RT 078 (A+B+CDT+), a RT originally only isolated from animals, particularly livestock, in the Northern hemisphere and also associated with more severe disease – See more at: http://microbiology.publish.csiro.au/?paper=MA14008#sthash.RVdbbLhF.dpuf
Another potential explanation for the increase in CDI rates is the emergence of new strains. RT 244 was first identified in Australia in 2011 and preliminary data suggested it was associated with more severe disease. This was recently supported by De Almeida et al.12 who, after identifying a new strain in New Zealand as RT 244, performed a case-control study of cases with CDI due to this RT. Cases had more severe disease (OR 9.33; P = 0.015) and were more likely to have community-associated infections (prevalence ratio 3.33; P = 0.078) when compared with controls who were infected with other C. difficile strains. Like RT 027, RT 244 produces more toxins A and B as a result of a single base pair deletion in tcdC (a gene involved in regulation of toxin A and B production), as well as binary toxin. RT 244 is therefore identified as a putative RT 027 with the Cepheid Xpert® C. difficile/Epi system. Other emerging RTs in Australia include RT 251 (A+B+CDT+), which also appears to be closely related to RT 027, and RT 033 (ABCDT+), RT 126 (A+B+CDT+) and RT 127 (A+B+CDT+), which are closely related to RT 078 (A+B+CDT+), a RT originally only isolated from animals, particularly livestock, in the Northern hemisphere and also associated with more severe disease – See more at: http://microbiology.publish.csiro.au/?paper=MA14008#sthash.RVdbbLhF.dpuf
Another potential explanation for the increase in CDI rates is the emergence of new strains. RT 244 was first identified in Australia in 2011 and preliminary data suggested it was associated with more severe disease. This was recently supported by De Almeida et al.12 who, after identifying a new strain in New Zealand as RT 244, performed a case-control study of cases with CDI due to this RT. Cases had more severe disease (OR 9.33; P = 0.015) and were more likely to have community-associated infections (prevalence ratio 3.33; P = 0.078) when compared with controls who were infected with other C. difficile strains. Like RT 027, RT 244 produces more toxins A and B as a result of a single base pair deletion in tcdC (a gene involved in regulation of toxin A and B production), as well as binary toxin. RT 244 is therefore identified as a putative RT 027 with the Cepheid Xpert® C. difficile/Epi system. Other emerging RTs in Australia include RT 251 (A+B+CDT+), which also appears to be closely related to RT 027, and RT 033 (ABCDT+), RT 126 (A+B+CDT+) and RT 127 (A+B+CDT+), which are closely related to RT 078 (A+B+CDT+), a RT originally only isolated from animals, particularly livestock, in the Northern hemisphere and also associated with more severe disease – See more at: http://microbiology.publish.csiro.au/?paper=MA14008#sthash.RVdbbLhF.dpuf

– See more at: http://microbiology.publish.csiro.au/?paper=MA14008#sthash.RVdbbLhF.dpuf

They found that the patients with the RT244 strain had more severe disease, renal impairment and hypoalbuminemia compared with non-RT244 patients. These patients also were more likely to die: They had a 30-day mortality of 42% and four of the five deaths were attributed to CDI. There were no deaths among patients with non-RT244 strains. Patients with the RT244 strain were 13 times more likely to die compared with those with non-RT244 strains.

In a phylogenomic analysis, the researchers found that the RT244 strain is in the same genetic clade as the strain RT027 (clade 2). In further analyses, the researchers found that the RT244 strain produced a variant toxin B, which may be the contributing factor to the strain’s virulence.

“The overall clinical significance of RT244 cannot be clearly determined at present,” the researchers wrote in Clinical Infectious Diseases. “At our laboratory, C. difficile RT244 has spontaneously declined and the epidemiological data available to us provided no clear evidence for the source of the strain, how it disseminated in our community or why its incidence has declined. Further studies are required to answer these questions, and to better understand the virulence of the strain, and its potential to become endemic and to cause further outbreaks.”

Lim S. Clin Infect Dis. 2014;doi:10.1093/cid/ciu203.

April 2014

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