Risk Factors for Recurrent Staphylococcus aureus Bacteremia

Abstract

Background: To understand the clinical, bacterial, and host characteristics associated with recurrent Staphylococcus aureus bacteremia (R-SAB), patients with R-SAB were compared to contemporaneous patients with a single episode of SAB (S-SAB).

Methods: All SAB isolates underwent spa genotyping. All isolates from R-SAB patients underwent pulsed-field gel electrophoresis (PFGE). PFGE-indistinguishable pairs from 40 patients underwent whole genome sequencing (WGS). Acute phase plasma from R-SAB and S-SAB patients was matched 1:1 for age, race, sex, and bacterial genotype, and underwent cytokine quantification using 25-analyte multiplex bead array.

Results: R-SAB occurred in 69 (9.1%) of the 756 study patients. Of the 69 patients, 30 experienced relapse (43.5%) and 39 reinfection (56.5%). Age, race, hemodialysis dependence, presence of foreign body, methicillin-resistant Staphyloccus aureus, and persistent bacteremia were individually associated with likelihood of recurrence. Multivariate risk modeling revealed that black hemodialysis patients were nearly 2 times more likely (odds ratio [OR] = 9.652 [95% confidence interval [CI], 5.402-17.418]) than white hemodialysis patients (OR = 4.53 [95% CI, 1.696-10.879]) to experience R-SAB. WGS confirmed PFGE interpretations in all cases. Median RANTES (regulated on activation, normal T cell expressed and secreted) levels in acute phase plasma from the initial episode of SAB were higher in R-SAB than in matched S-SAB controls (P = .0053, false discovery rate < 0.10).

Conclusion: This study identified several risk factors for R-SAB. The largest risk for R-SAB is among black hemodialysis patients. Higher RANTES levels in R-SAB compared to matched controls warrants further study.

Keywords: Staphylococcus aureus; bacteremia; health disparity; recurrence; whole genome sequencing.

Figure 1.

Flow of classification of study patients based on PFGE and cutoff value of the time between the first episode of SAB) and the subsequent episode of recurrent SAB (ΔT). Abbreviations: PFGE, pulsed-field gel electrophoresis; SAB, S. aureus bacteremia.

Figure 2.

Distribution of the number of SNPs for isolate pairs between individuals with fewer than 200 SNPs (between) compared to pairs of isolates from the same individual with a PFGE match (within). Supplementary Figure 5 indicates that the isolate pairs between individuals are a visual PFGE match. Abbreviations: PFGE, pulsed-field gel electrophoresis; SNP, single-nucleotide polymorphism.

Figure 3.

A, Comparison of baseline plasma RANTES level between patients with recurrent SAB) and age/sex/race/genotype-matched patients with a resolving single episode of SAB. B, Difference in RANTES values between recurrent SAB and their matched single SAB. We also examined a more conservative set of fewer than 100 SNPs. Here the median for the “across individual” set was 74 and still significantly different from the “same individual” pairs (P < .0001). Abbreviations: RANTES, regulated on activation, normal T cell expressed and secreted; SAB, Staphylococcus aureus bacteremia; SNP, single-nucleotide polymorphism.