Clinical and Molecular Analysis of Recurrent Gram-Negative Bloodstream Infections

Abstract Background The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. Methods We used a prospectively ascertained cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (both pulsed field gel electrophoresis [PFGE] and whole genome sequencing [WGS]) was used to define whether these episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors associated with recurrence. Results Of the 1423 patients with GNB-BSI that met criteria for inclusion in this study, 60 (4%) had recurrent GNB-BSI. Non-white race (OR: 2.35; CI95% 1.38-4.01; p = 0.002), admission to a surgical service (OR: 2.18; CI95% 1.26-3.75; p = 0.005) and presence of an indwelling cardiac device (OR: 2.73; CI95% 1.21-5.58, p = 0.009) 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 (30/48) and 38% were due to reinfection (18/48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47/48) of cases. Median time to relapse and reinfection was similar (113 days [IQR: 35-222 days] vs. 174 days [IQR: 69-599 days], p = 0.13). Presence of a cardiac device was associated with relapse (Relapse: 7/27 [26%]; Non-relapse: 65/988 [7%]; p = 0.002). Conclusions In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Presence of a cardiac device was a risk factor for relapse.