A network analysis of carbapenem-resistant Klebsiella pneumoniae among healthcare facilities

Abstract

With limited treatments for carbapenem-resistant Klebsiella pneumoniae (CRKp), curtailing transmission is critical. We applied a network analysis using epidemiological admission data and bacterial genetics to characterize CRKp spread among patients in 16 acute care hospitals linked to 217 other healthcare facilities in the United States. Patients with diagnosed CRKp infection were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a prospective, observational study conducted from 12/2011 to 6/2016. A network analysis was performed using epidemiological admission data and bacterial genetics to characterize putative CRKp transmission among patients across various healthcare facilities and the community. Overall, 347/526 patients (66%) had a putative transmission link to at least one other patient within the network. Most transmission chains were small (i.e., between 2 patients); however, the largest included 172 patients diagnosed over 1575 days. One-third of patients shared a genetically similar CRKp isolate with another patient but had no observed epidemiological linkages at any healthcare location. Patients with CRKp are part of extensive regional networks involving a large number of non-hospital healthcare settings such as skilled nursing facilities. Thus, controlling spread necessitates integrated surveillance and control initiatives at regional and national levels in addition to institution-specific approaches.

Keywords: Antimicrobial resistance; Bacterial typing; Enterobacterales; Infection control; Network analysis; Nosocomial infections.

Fig. 1

Circle shows the phylogenetic population structure of CRKp isolates using pairwise core single nucleotide polymorphisms for all 630 CRKp isolates. Multilocus sequence type (MLST) and presence of carbapenemases and extended-spectrum beta-lactamases are identified as color-coded bars for each CRKp isolate.

Fig. 2

Putative CRKp transmission linking patients across healthcare facilities. Each node (circle) represents one patient (n = 347), colored by the acute care hospital (ACH) where the patient was diagnosed with CRKp. Patients are grouped by state based on the ACH location; shaded backgrounds indicate that the component (linked group of patients) comprises multiple states. Putative transmission of CRKp are shown as lines connecting nodes (i.e. edges) (N = 1,069 edges) with the edge color indicating the estimated transmission likelihood (1–100%) based on meeting the threshold for the length of time between admissions at the same facility (pre-admission, ACH, or post-discharge) and the CRKp genetic distance between isolates. Edge direction (arrow) goes from the patient with the earlier positive CRKp culture date to the patient with the later CRKp isolation date. Patients who were admitted to the same facility during the 4.5-year study period have solid edges between them, while patients who never occupied the same facility but have genetically similar CRKp (i.e. 10 SNPs) are linked by dotted lines. A change in node color between adjacent nodes with a solid line therefore indicates that facility overlap was not at the ACH of diagnosis. Singletons (cohort members with no estimated potential transmission linkages) are not shown.