Article Figures & Data
Figures
- FIG 1
Study population. Adult patients in the University of Michigan Health System’s ICU and adult hematology/oncology patients were screened for colonization and extraintestinal infection with K. pneumoniae between July and October 2014 (n = 1,765), divided into “infected” and “not infected” groups, and further divided into “colonized” and “not colonized.” The number of infections by body site are shown in boxes; one colonized patient met case definitions for both pneumonia and UTI.
- FIG 2
Receiver operator characteristic curve for a multivariable model of risk factors for clinical infection. Multiple logistic regression of K. pneumoniae infection was used to generate a predictive model using five patient variables (Table 4). Bars and shaded areas of ROC curves represent bootstrapped 95% confidence intervals (10,000 replicates) for specificity at each level of sensitivity (AUC, 0.78; 95% CI, 0.72 to 0.84).
- FIG 3
Phylogenetic tree for wzi sequence of patient rectal swab isolates. Unique patients (P) are numbered (P1 to P40). A rectal swab (S) isolate is indicated after the patient number and immediately before the isolate number (e.g., S463 is stool isolate number 463). The isolate wzi type is indicated, and novel alleles are designated unknown by UK. A total of 110 rectal swab isolates from 40 unique patients were tested for strain type using wzi gene sequencing. A total of 43 different wzi types of strains were identified. Rectal swab isolates for patients with K. pneumoniae colonization prior to infection were all included in the analysis (P1 to P16; colored font). The scale bar represents the amount of genetic change; 0.01 equals 1 change per 100 nucleotide sites. The numbers next to each node are the percentage of iterations that recovered the same node.
- FIG 4
Core genome similarity between infecting and colonizing strains within patients. Patients who had concordant colonizing and infecting isolates based on wzi sequencing were further analyzed by WGS and core genome MLST and are represented by a unweighted pair group method using average linkages dendrogram along with isolate number, MLST type (ST), wzi type, and body site of culture (source). Each color represents an individual patient. Isolates 463 and 1946 (patient 1) were discordant by wzi and were included as a control.
Tables
- TABLE 1
Demographic characteristics of patients with and without infection
Variable No. (%) or mean ± SD P valuea Infected (n = 39) No infection (n = 1,726) Female 19 (48.7) 835 (48.3) >0.99 White race 31 (79.5) 1,438 (83.3) 0.488 Hispanic 0 (0) 33 (1.9) 0.984 Prior admit (28 days) 27 (69.2) 947 (54.8) 0.079 Length of stay (days) 14.9 ± 14.9 11.6 ± 18.9 0.01 Neurologic disorderb 6 (15.4) 109 (6.3) 0.029 Fluid and electrolyte disorderb 20 (51.3) 569 (33) 0.019 Renal diseaseb 5 (12.8) 286 (16.6) 0.533 Liver diseaseb 5 (12.8) 112 (6.5) 0.123 Alcohol abuseb 1 (2.6) 94 (5.4) 0.442 Solid organ tumorb 13 (33.3) 403 (23.3) 0.151 Diabetes mellitus, uncomplicatedb 8 (20.5) 242 (14) 0.218 K. pneumoniae colonization 21 (53.8) 385 (22.3) <0.001 Central line before colonization 27 (69.2) 963 (55.8) 0.099 Antibiotic exposurec 5 (12.8) 453 (26.2) 0.067 Aminoglycoside 0 (0) 178 (10.3) 0.984 Fluoroquinolone 0 (0) 0 (0) NA Macrolide 2 (5.1) 151 (8.7) 0.433 Cephalosporin 1 (2.6) 139 (8.1) 0.237 Carbapenem 0 (0) 0 (0) NA Clindamycin 2 (5.1) 97 (5.6) 0.895 Age (yrs) 62.7 ± 12.8 58.2 ± 16.1 0.078 Hemoglobin, baseline (g/dl) 10.4 ± 2.4 11.1 ± 2.5 0.062 Platelets, baseline (×103/µl) 167.9 ± 90.9 207.3 ± 115.5 0.012 Albumin, baseline (g/dl) 3.3 ± 0.6 3.5 ± 0.6 0.009 Body mass index (kg/m2) 27 ± 6.7 29.5 ± 9.5 0.128 - TABLE 2
Prior colonization with K. pneumoniae versus subsequent infection
Infection status No. (%)
colonizedNo. (%)
not colonizedTotal OR (95% CI)
for infectionP valuea Infection 21 (5.2) 18 (1.3) 39 4.06 (2.14–7.7) <0.001 No infection 385 (94.8) 1,341 (98.7) 1,726 Total 406 (23) 1,359 (77) 1,765 ↵a Determined using the Fisher's exact test.
- TABLE 3
Association with prior colonization for each site of infection
Site of infection Colonization frequency (%) OR (95% CI) P valuea Infected Not infected Blood 7/11 (64) 399/1,754 (23) 5.94 (1.73–20.41) 0.005 Respiratory 8/15 (53) 398/1,750 (23) 3.88 (1.40–10.77) 0.01 Urine 7/14 (50) 399/1,751 (23) 3.39 (1.18–9.72) 0.024 ↵a P values were obtained using Fisher’s exact test.
- TABLE 4
Multiple logistic regression model of risk factors for infection
Variable OR 95% CI P value Colonized 4.01 2.08–7.73 <0.001 Fluid and electrolyte disordera 2.37 1.22–4.59 0.011 Neurologic disordera 3.31 1.28–8.54 0.013 Prior admit (28 days) 2.16 1.04–4.48 0.038 Baseline platelet count/100 units (×103/µl)b 0.73 0.53–1.01 0.058
Figure S1
The wzi sequencing method has similar discriminatory power as MLST. Phylogenetic trees based on MLST results (a) and wzi sequencing results (b) are shown, each distinguishing 16 sequence types among 20 K. pneumoniae isolates. The scale bar represents the amount of genetic change. The numbers next to each node are the percentages of iterations that recovered the same node. Download Figure S1, TIF file, 0.2 MB.
Copyright © 2016 Martin et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
Figure S2
Phylogenetic trees of rectal swab and infecting isolates based on wzi gene sequencing. Phylogenetic trees, built using the neighbor-joining method, for infecting and colonizing isolates from patients with BSI (a), pneumonia (PNA) (b), and UTI (c) are shown along with the fraction of patients with a concordant colonizing-infecting isolate pair. Unique patients are indicated by different colors and labeled as follows: patient number_ isolate number_wzi allele (unless a novel allele), _K-type (if known), where the isolate number prefixes indicate rectal swab (S), blood (B), respiratory (R), or urine (U). The scale bar represents the amount of genetic change. The numbers next to each node are the percentages of iterations that recovered the same node. Download Figure S2, PDF file, 1.1 MB.
Copyright © 2016 Martin et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
Figure S3
Concordant colonizing-infecting isolate pairs show high core genome allelic similarity. The minimum-spanning tree based on the core genome MLST profiles, onto which the number of allelic differences between isolates, is indicated along the links. Note that the numbers are not additive, and that the tree should not be interpreted as depicting phylogenetic relationships. Isolate names are shown in bold. Each color represents an individual patient. Isolates 463 and 1946 (patient 1) were discordant by wzi and included as a control. cgMLST profiles of isolates within a single circle were totally identical. Download Figure S3, PDF file, 0.6 MB.
Copyright © 2016 Martin et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
Table S1
Categorical agreement of colonizing-infecting isolate pairs in case patients. Download Table S1, DOCX file, 0.02 MB.
Copyright © 2016 Martin et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
Text S1
wzi alleles used to construct phylogenetic trees. Download Text S1, DOC file, 0.1 MB.
Copyright © 2016 Martin et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
