Follow-Up Blood Cultures in Streptococcal and Enterococcal Bacteremia: A Systematic Review of Persistent Bacteremia and Its Clinical Significance

Follow-up blood cultures are frequently obtained after streptococcal or enterococcal bloodstream infection, although their clinical value remains uncertain.This systematic review evaluated the frequency, predictors, and clinical significance of persistent bacteremia among adults undergoing repeat blood culture sampling.MEDLINE via PubMed, Embase, Scopus, and Web of Science Core Collection were searched from inception through February 28, 2026.The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement.Eligible observational studies reported follow-up culture findings, predictors of persistence, clinical outcomes, or management consequences.Six studies comprising 1,668 participants were included: five retrospective studies and one prospective multicenter cohort.Findings were synthesized narratively because of clinical and methodological heterogeneity.Reported persistent bacteremia or positive follow-up culture frequencies ranged from 3.2% to 22.2%, with important differences in definitions, sampling intervals, and antimicrobial exposure.Streptococcal persistence varied by species and was associated with endocarditis and other deep-seated infections.Enterococcal persistence was associated with endocarditis, hematologic malignancy, severe neutropenia, positivity of all index culture bottles, and inadequate source control.In the prospective VENOUS I cohort, microbiological failure occurred in 16.8% and independently predicted in-hospital mortality (adjusted hazard ratio 2.40, 95% confidence interval 1.34-4.31),whereas mortality associations in other cohorts were inconsistent or imprecise.Some studies reported longer treatment, hospitalization, or greater relapse among persistently positive patients; evidence documenting direct management changes was limited.Quality in Prognosis Studies assessment classified four studies as having moderate overall risk of bias and two as high risk, principally reflecting selection, confounding, and analytical limitations.Persistent positivity may identify patients at increased clinical risk, but these associations do not establish whether routine or selective sampling improves outcomes or whether omitting cultures is safe.A risk-adapted testing strategy remains a hypothesis requiring prospective validation.