Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective, matched cohort study

Abstract

We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocompetent, nontransplant recipients. Fifty-five transplant recipients (GNB n = 29; SAB n = 26) and 225 nontransplant recipients (GNB n = 114; SAB n = 111) were included for clinical analysis. Transplant GNB had a significantly lower incidence of septic shock than nontransplant GNB (10.3% vs 30.7%, p = .03). Thirty-day mortality did not differ significantly between transplant and nontransplant recipients with GNB (10.3% vs 15.8%, p = .57) or SAB (0.0% vs 11.7%, p = .13). Next, transplant patients were matched 1:1 with nontransplant patients for the chemokine and cytokine analysis. Five cytokines and chemokines were significantly lower in transplant GNB vs nontransplant GNB: IL-2 (median [IQR]: 7.1 pg/ml [7.1, 7.1] vs 32.6 pg/ml [7.1, 88.0]; p = .001), MIP-1β (30.7 pg/ml [30.7, 30.7] vs 243.3 pg/ml [30.7, 344.4]; p = .001), IL-8 (32.0 pg/ml [5.6, 53.1] vs 59.1 pg/ml [39.2, 119.4]; p = .003), IL-15 (12.0 pg/ml [12.0, 12.0] vs 12.0 pg/ml [12.0, 126.7]; p = .03), and IFN-α (5.1 pg/mL [5.1, 5.1] vs 5.1 pg/ml [5.1, 26.3]; p = .04). Regulated upon Activation, Normal T Cell Expressed and Secreted (RANTES) was higher in transplant SAB vs nontransplant SAB (mean [SD]: 750.2 pg/ml [194.6] vs 656.5 pg/ml [147.6]; p = .046).

Keywords: clinical research/practice; cytokines/cytokine receptors; immunosuppression/immune modulation; infection and infectious agents - bacterial; infectious disease; organ transplantation in general; translational research/science.

Figure 1:. Study design

Clinical analysis was performed on the 55 transplant cases and 227 eligible controls (Boxes B and C). Corresponding tables for this comparison are tables 1–3. Chemokine and cytokine analysis was performed on the 55 transplant cases and 60 matched controls (Boxes B and D). Corresponding tables for this comparison are tables 4–5. SAB, S. aureus bacteremia; GNB, gram-negative bacteremia

Figure 2A-F:. Cytokine and chemokine levels differ by transplant status in patients with gram-negative bacteremia and S. aureus bacteremia.

GNB, gram-negative bacteremia; SAB, S. aureus bacteremia; ns, not significant. Box plot extends from 25^th to 75^th percentile. The line in middle of box denotes median. Whiskers extend to 10^th and 90^th percentile. P-values were determined using Wilcoxon Rank Sum tests. Analyte concentrations below the lower limit of quantitation were replaced with one-half of the lower limit of quantitation. Thus when multiple patients had cytokine levels below the limit of detection, the 1^st and 3^rd quartiles were identical to the median.