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Background The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. Methods We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (pulsed-field gel electrophoresis [PFGE] and whole-genome sequencing [WGS]) was used to determine whether episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors for recurrence. Results Of the 1423 patients with GNB-BSI in this study, 60 (4%) had recurrent GNB-BSI. Non-White race (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.38–4.01; P = .002), admission to a surgical service (OR, 2.18; 95% CI, 1.26–3.75; P = .005), and indwelling cardiac device (OR, 2.73; 95% CI, 1.21–5.58; P = .009) were associated with increased risk for recurrent GNB-BSI. Among the 48 patients with recurrent GNB-BSI whose paired bloodstream isolates underwent genotyping, 63% were due to relapse (30 of 48) and 38% were due to reinfection (18 of 48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47 of 48) of cases. Median time to relapse and reinfection was similar (113 days; interquartile range [IQR], 35–222 vs 174 days; IQR, 69–599; P = .13). Presence of a cardiac device was associated with relapse (relapse: 7 of 27, 26%; nonrelapse: 65 of 988, 7%; P = .002). Conclusions In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Cardiac device was a risk factor for relapse.

Background Gram-negative bacteria bloodstream infections (GNB-BSI) are a significant cause of morbidity and mortality. Recurrent GNB-BSI is an incompletely understood phenomenon. In this study we identify risk factors for recurrent GNB-BSI. Methods Patients with GNB-BSI have been prospectively enrolled into the Bloodstream Infection Biorepository (BSIB) since 2002. From the BSIB, patients with >1 episode of GNB-BSI with the same bacterial species were identified. Chi-Square, Fisher Exact, and a multivariate linear regression models were used to identify clinical risk factors for recurrent GNB-BSI. Paired isolate samples from the initial and the recurrent episode of GNB-BSI in same patient underwent Pulsed Field Gel Electrophoresis (PFGE) to differentiate Relapse (paired isolates identical) from Reinfection (paired isolates different). Results Among the 1,423 unique patients with GNB-BSI enrolled from 2002- 2015, 60 (4.2%) experienced recurrent GNB-BSI with the same bacterial species. Median time to recurrent GNB-BSI was 133 d (IQR: 40-284.75 days). Causes of recurrent-GNB-BSI included Escherichia coli (38%), Klebsiella species (30%), Pseudomonas aeruginosa (12%), and Serratia marcescens (5%) and did not differ from causes of non-recurrent GNB-BSI (Figure 1). Risk factors for recurrent GNB-BSI included Black race (OR: 2.45 [CI: 1.43-4.20]), implanted cardiac device (OR: 2.39 [CI: 1.00-5.07]), and admission to surgical service (OR: 2.16 [CI 1.24-3.75]). Forty-eight isolate-pairs from 43 patients with recurrent GNB-BSI underwent PFGE, relapse occurred in 31 (65%) and reinfection occurred in 17 (35%). Risk factors for GNB-BSI relapse included cardiac device (OR: 3.7 [CI: 1.7-8.3]), and admission to surgical service (OR: 3.7 [CI:1.3-9.4]). Figure 1: Species Breakdown Proportional comparison of the Gram-negative bacterial species identified in patients with recurrent and non-recurrent bloodstream infections. Conclusion Recurrent GNB-BSI is an uncommon complication of GNB-BSI. Recurrent GNB-BSI is most often driven by relapse, as opposed to reinfection, and is associated with associated with black race, implanted cardiac devices and admission to surgical service. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant)

Rationale & Objective Staphylococcus aureus (S aureus) bacteremia (SAB) is associated with morbidity and mortality in patients receiving maintenance hemodialysis (HD). We evaluated changes in clinical and bacterial characteristics, and their associations with clinical outcomes with SAB in this population over a 21-year period. Study Design Prospective cohort study. Setting & Participants 453 hospitalized, non-neutropenic adults receiving maintenance HD who developed monomicrobial SAB between 1995 and 2015. Exposure Clinical characteristics and bacterial genotype. Outcome All-cause and SAB-attributable mortality, persistent bacteremia, and metastatic complications. Analytical Approach Proportions of participants experiencing each outcome were calculated overall and by calendar year. Secular trends were estimated using binomial risk regression, a generalized linear model with the log link function for a binomial outcome. Associations with outcomes were estimated using logistic regression. Results Over the 21-year study period, patients receiving maintenance HD experienced significant increases in age- and diabetes-adjusted SAB-attributable mortality (0.45% [95% CI, 0.36%-0.46%] per year), persistent bacteremia (0.86% [95% CI, 0.14%-1.55%] per year), metastatic complications (0.84% [95% CI, 0.11%-1.56%] per year), and infection with the virulent S aureus clone USA300 (1.47% [95% CI, 0.33%-2.52%] per year). Over time, the suspected source of SAB was less likely to be a central venous catheter (−1.32% [95% CI, −2.05 to −0.56%] per year) or arteriovenous graft (−1.08% [95% CI, −1.54 to −0.56] per year), and more likely to be a nonvascular access source (1.89% [95% CI, 1.29%-2.43%] per year). Patients with a nonvascular access suspected source of infection were more likely to die as a result of their S aureus infection (OR, 3.20 [95% CI, 1.36-7.55]). The increase in USA300 infections may have contributed to the observed increase in persistent bacteremia (OR, 2.96 [95% CI, 1.12-7.83]) but did not explain the observed increases in SAB-attributable mortality (OR, 0.83 [95% CI, 0.19-3.61]) or metastatic complications (OR, 1.34 [95% CI, 0.53-3.41]). Limitations Single-center, inpatient cohort. Conclusions The clinical and molecular epidemiology of SAB in patients receiving maintenance HD has changed over time, with an increase in SAB-attributable mortality and morbidity despite a decline in catheter-related infections.