Increased Relative Abundance of Klebsiella pneumoniae Carbapenemase-producing Klebsiella pneumoniae Within the Gut Microbiota Is Associated With Risk of Bloodstream Infection in Long-term Acute Care Hospital Patients

Clin Infect Dis. 2019 May 30;68(12):2053-2059. doi: 10.1093/cid/ciy796.


Background: An association between increased relative abundance of specific bacterial taxa in the intestinal microbiota and bacteremia has been reported in some high-risk patient populations.

Methods: We collected weekly rectal swab samples from patients at 1 long-term acute care hospital (LTACH) in Chicago from May 2015 to May 2016. Samples positive for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) by polymerase chain reaction and culture underwent 16S rRNA gene sequence analysis; relative abundance of the operational taxonomic unit containing KPC-Kp was determined. Receiver operator characteristic (ROC) curves were constructed using results from the sample with highest relative abundance of KPC-Kp from each patient admission, excluding samples collected after KPC-Kp bacteremia. Cox regression analysis was performed to evaluate risk factors associated with time to achieve KPC-Kp relative abundance thresholds calculated by ROC curve analysis.

Results: We collected 2319 samples from 562 admissions (506 patients); KPC-Kp colonization was detected in 255 (45.4%) admissions and KPC-Kp bacteremia in 11 (4.3%). A relative abundance cutoff of 22% predicted KPC-Kp bacteremia with sensitivity 73%, specificity 72%, and relative risk 4.2 (P = .01). In a multivariable Cox regression model adjusted for age, Charlson comorbidity index, and medical devices, carbapenem receipt was associated with achieving the 22% relative abundance threshold (P = .044).

Conclusion: Carbapenem receipt was associated with increased hazard for high relative abundance of KPC-Kp in the gut microbiota. Increased relative abundance of KPC-Kp was associated with KPC-Kp bacteremia. Whether bacteremia arose directly from bacterial translocation or indirectly from skin contamination followed by bloodstream invasion remains to be determined.

Keywords: bloodstream infection; carbapenemase-producing Klebsiella pneumoniae; intestinal domination; long-term acute care hospital; microbiome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacteremia*
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics*
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Cross Infection / epidemiology*
  • Female
  • Gastrointestinal Microbiome*
  • Hospitals
  • Humans
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / epidemiology*
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • ROC Curve
  • beta-Lactamases / biosynthesis
  • beta-Lactamases / genetics*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • beta-Lactamases
  • carbapenemase