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Phylogenetic tracking benefits C. difficile surveillance in hospitals
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A Clostridium difficile surveillance system based upon whole-genome phylogenetics may successfully monitor the disease’s spread among symptomatic hospital patients, according to recent data.
“Unlike other common health care-associated pathogens, C. difficile produces highly resistant and transmissible spores that confound standard infection control measures,” Nitin Kumar, PhD, postdoctoral fellow at the Wellcome Trust Sanger Institute, Hinxton, United Kingdom, and colleagues wrote. “Both asymptomatic carriers and symptomatic patients can excrete spores leading to C. difficile spread by direct or indirect modes of transmission. Conventional genotypic methods used for studying C. difficile transmission dynamics and epidemiology … are not sufficient to discriminate between genetically monomorphic lineages.”
Analysis identifies risk factors, ‘super-spreaders’
From July 2008 to May 2010, Kumar and colleagues monitored adult C. difficile patients receiving care at the 870-bed Royal Liverpool and Broadgreen University Hospitals NHS Trust. Studied patients had a C. difficile episode, defined as health care-associated diarrhea, received a positive toxin test and had infection confirmed by clinicians following national guidelines. Confirmed isolates of PCR-ribotype 027 were sequenced for phylogenetic information, the results of which were combined with patient data to identify epidemiological events and create a hospital ward-based transmission model.
Kumar and colleagues confirmed 801 hospital and community samples positive for C. difficile through the study period. Of these, 446 isolates were obtained and underwent PCR-ribotyping for further analysis, which revealed C. difficile 027/ST1 to be the predominantly identified ribotype.
There were 32 transmission events identified through the model, 66% of which were due to patients inhabiting a previously discharged patient’s ward. The researchers also identified a ward and several highly contagious patients associated with increased transmission, and observed a relationship between shorter infection periods and more contagious patients. Whole-genome SNP phylogenetic analysis was able to accurately identify 27 SNP genotypes within C. difficile 027/ST1, and subsequently delineate their evolutionary relationships.
These findings highlight the strengths of including whole-genome phylogenetics into epidemiology, the researchers wrote, and can be of great use in identifying “super-spreaders” and the various influences on C. difficile infection within hospitals.
“Phylogenetic SNP genotyping was able to detect precise patient-to-patient transmission and recurrent events of [C. difficile infection],” Kumar and colleagues wrote. “We envisage that genome databases with relevant metadata will serve as a common, open-access resource that can be exploited to identify and track C. difficile within their local region through whole-genome sequencing or other comparative measures such as SNP-typing.”
Whole-genome sequencing supplements traditional epidemiology
These findings are supported by an investigation into a nosocomial outbreak of Acinetobacter baumannii published last year in Genome Medicine, which found that combining whole-genome sequencing and epidemiologic investigation improved infection control within the Queen Elizabeth Hospital in Birmingham, England.
During a 2011 outbreak, researchers switched from strictly traditional methods of infection prevention and control to an approach involving whole-genome sequencing. They identified 114 multidrug-resistant Acinetobacter isolates from routine clinical samples, and tested these for bacterial identification and antibiotic susceptibility, with multidrug resistance defined as resistance to three or more classes of antibiotics. The researchers determined that 74 isolates acquired from 49 patients and 10 environmental isolates were genomically similar enough to the reference outbreak strain — pulsotype 27 — to be considered part of the outbreak.
Along with ruling out 18 isolates from the outbreak, joint method recreated potential transmission events that connected all but 10 of the patients, and established links between the clinical and environmental isolates. Improvements in environmental decontamination protocols were implemented after a contaminated bed and a burn unit were identified as vehicles of transmission, leading the researchers to conclude that whole-genome sequencing could play a valuable role in the prevention and control of future nosocomial infections.
“[Whole-genome sequencing] is now poised to make an impact on hospital infection prevention and control, delivering cost-effective identification of routes of infection within a clinically relevant time frame and allowing infection control teams to track, and even prevent, the spread of drug-resistant hospital pathogens,” the researchers wrote. – by Dave Muoio
Disclosure: The researchers report no relevant financial disclosures.
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