Clinical and Molecular Analyses of Recurrent Gram-Negative Bloodstream Infections

Author:

Bock Andrew1,Hanson Blake M234,Ruffin Felicia5,Parsons Joshua B5,Park Lawrence P56,Sharma-Kuinkel Batu5,Mohnasky Michael7,Arias Cesar A28,Fowler Vance G59,Thaden Joshua T5

Affiliation:

1. Duke University School of Medicine , Durham, North Carolina , USA

2. Division of Infectious Diseases, Department of Medicine, Houston Methodist Hospital , Houston, Texas , USA

3. Center for Antimicrobial Resistance and Microbial Genomics, McGovern Medical School, University of Texas Health Science Center , Houston, Texas , USA

4. Division of Infectious Disease, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center , Houston, Texas , USA

5. Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine , Durham, North Carolina , USA

6. Duke Global Health Institute , Durham, North Carolina , USA

7. University of North Carolina–Chapel Hill School of Medicine , Chapel Hill, North Carolina , USA

8. Center for Infectious Diseases, Houston Methodist Research Institute , Houston, Texas , USA

9. Duke Clinical Research Institute , Durham, North Carolina , USA

Abstract

Abstract 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.

Funder

National Institute of Allergy and Infectious Diseases

National Institutes of Health

National Center for Advancing Translational Sciences

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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