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Genomic Clues Clarify Drug-Resistant Klebsiella Transmissions During Chicago Area Outbreak

NEW YORK (GenomeWeb) – A retrospective genomic and epidemiologic analysis is offering a look at the transmission patterns that occurred during an American outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) nearly a decade ago.

As they reported online today in Science Translational Medicine, researchers from Rush University Medical Center, the University of Michigan, and elsewhere turned to whole-genome sequencing, phylogenetics, and epidemiology to tease out transmission chains and events that occurred during a CRKP outbreak in the Chicago area in 2008 that involved 40 patients at dozens of healthcare facilities in Illinois and Indiana.

"This approach might be particularly useful in identifying pathways of transmission soon after emergence of a superbug in a region. The earlier we can intervene to contain an outbreak, the more likely it is that we can eradicate it," senior author Mary Hayden, a microbiology and immunology researcher and director of clinical microbiology at Rush University Medical Center, said in a statement.

Consistent with results from a prior analysis, she and her colleagues explained, the current study suggests patient transfers between regional acute care hospitals, nursing homes, and long-term care facilities subsequently fueled an outbreak that began with a single infected individual in 2007.

"Examination of the genomic transmission network in the context of patient-sharing networks confirmed the role of patient sharing in the outbreak and demonstrated how a handful of patient transfers could seed a regional outbreak," the authors wrote.

The researchers' phylogenetic analysis, based on variants and small insertions and deletions in 41 CRKP isolates from 31 affected individuals, supported the notion that a single CRKP clone in the 258 sequence type began spreading in 2007 before diversifying into A, B, and C clades. Using the Illumina MiSeq instrument, the researchers also sequenced a previously unanalyzed isolate from the first individual identified with CRKP in the region.

"Because this was the first outbreak of CRKP in the Chicago region, we decided to try to trace its initial movements based on patient transfers and whole-genome sequencing of samples," first author Evan Snitkin, a microbiology, immunology, and infectious diseases researcher at the University of Michigan, said in a statement. "If we can understand what drives transmission in a region, we hope to be able to intervene to prevent further spread."

When they delved into the phylogeny, the researchers found that the CRKP clade A often contained isolates from individuals infected at long-term acute care hospitals, while many of the acute care hospital isolates fell in clade B. On the other hand, the C clade contained isolates identified at a range of different healthcare settings.

The team went on to investigate CRKP transmission chains to more fully understand interactions between patients and between the healthcare sites involved. For example, the results suggested the facilities affected by the outbreak each experienced multiple CRKP introductions, with patient transfers from nursing homes adding to transmission events centered at long-term acute care and acute care hospitals.

"[O]ur genomic analysis yielded a high-resolution transmission map that allowed for discrimination between intra- and inter-facility transmission events, provided insight into the direction of transmission between facilities, and verified the estimated date of introduction of CRKP to the region," the authors wrote.

The researchers cautioned that although CRKP is typically contained to healthcare settings in the US, other outbreaks may involve organisms found in both healthcare and community settings. Consequently, they argued that similar transmission analyses of other drug-resistant bugs "will require high-quality epidemiologic data that probe the transmission pathways relevant to the organism under study."