title: Molecular Epidemiology of Colonizing and Infecting Isolates ofKlebsiella pneumoniae.
abstract: Klebsiella pneumoniaeis among the most common causes of hospital-acquired infections and has emerged as an urgent threat to public health due to carbapenem antimicrobial resistance.K. pneumoniaecommonly colonizes hospitalized patients and causes extraintestinal infections such as urinary tract infection, bloodstream infection (septicemia), and pneumonia. If colonization is an intermediate step before infection, then detection and characterization of colonizing isolates could enable strategies to prevent or empirically treatK. pneumoniaeinfections in hospitalized patients. However, the strength of the association between colonization and infection is unclear. To test the hypothesis that hospitalized patients become infected with their colonizing strain, 1,765 patients were screened for rectal colonization withK. pneumoniae, and extraintestinal isolates from these same patients were collected over a 3-month period in a cohort study design. The overall colonization prevalence was 23.0%. After adjustment for other patient factors, colonization was significantly associated with subsequent infection: 21 of 406 (5.2%) colonized patients later had extraintestinal infection, compared to 18 of 1,359 (1.3%) noncolonized patients (adjusted odds ratio [OR], 4.01; 95% confidence interval, 2.08 to 7.73;P< 0.001). Despite a high diversity of colonizing isolates, 7/7 respiratory, 4/4 urinary, and 2/5 bloodstream isolates from colonized patients matched the patient corresponding rectal swab isolates, based onwzicapsular typing, multilocus sequence typing (MLST), and whole-genome sequence analysis. These results suggest thatK. pneumoniaecolonization is directly associated with progression to extraintestinal infection.IMPORTANCEK. pneumoniae commonly infects hospitalized patients, and these infections are increasingly resistant to carbapenems, the antibiotics of last resort for life-threatening bacterial infections. To prevent and treat these infections, we must better understand howK. pneumoniaecauses disease and discover new ways to predict and detect infections. This study demonstrates that colonization withK. pneumoniaein the intestinal tract is strongly linked to subsequent infection. This finding helps to identify a potential time frame and possible approach for intervention: the colonizing strain from a patient could be isolated as part of a risk assessment, and antibiotic susceptibility testing could guide empirical therapy if the patient becomes acutely ill.
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Rebekah M
authors: RM
authors: Martin
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Jie
authors: J
authors: Cao
authors: Institut Pasteur, Microbial Evolutionary Genomics, Paris, France.
authors: Sylvain
authors: S
authors: Brisse
authors: Institut Pasteur, Microbial Evolutionary Genomics, Paris, France.
authors: Virginie
authors: V
authors: Passet
authors: BRCF Bioinformatics Core, University of Michigan, Ann Arbor, Michigan, USA.
authors: Weisheng
authors: W
authors: Wu
authors: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
authors: Lili
authors: L
authors: Zhao
authors: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Preeti N
authors: PN
authors: Malani
authors: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA; Section of Infectious Diseases, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.
authors: Krishna
authors: K
authors: Rao
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Michael A
authors: 0000-0003-2507-6987
authors: MA
authors: Bachman
keywords: Klebsiella; MLST; cgMLST; colonization; infection; pneumonia; whole-genome sequencing; wzi