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

Abstract

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.

Figure 1.

Receiver operating characteristic curve analysis of the relationship between relative abundance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) and subsequent KPC-Kp bloodstream infection. Abbreviation: KPC-Kp, Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae.

Figure 2.

Chronological change of relative abundance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) in the gut microbiota of 11 patients with KPC-Kp bacteremia. This operational taxonomic unit (OTU) contained a single unique sequence that matched various Enterobacteriaceae family members, including the 16S rRNA gene sequences from K. pneumoniae. It contained several exact matches to at least 1 copy of the 16S rRNA gene sequence in genomes from several variants of K. pneumoniae ST258, confirming that the canonical KPC-Kp strains belonging to ST258 would fall into this OTU. Each panel shows data for a single patient’s admission. Dot markers indicate the relative abundance of KPC-Kp (%) measured on the hospital day indicated. Arrows indicate date of first positive KPC-Kp blood culture. For patients with multiple positive blood cultures (patients 3, 7, 9), another arrow was added only if new infection was suspected (bacteremia episodes separated by ≥2 weeks) based on National Healthcare Safety Network surveillance definitions [29]. Abbreviations: KPC-Kp, Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae; Pt, patient.