Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

Objectives The utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit, but may be limited by single-center designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. Methods Adult patients with GN-BSI hospitalized between April-2017 and December-2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay (LOS), and number of days alive and out of hospital at 30 (DAOH30) and 90 (DAOH90) days. Results 34,100 patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range 10.0–29.7%, range 0–66.1%) across 101 hospitals; this correlated with positivity and contamination rate. 890 (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully-adjusted model, there was no association between FUBC and mortality (HR 0.97, 95% CI 0.90–1.04). Patients with FUBC had significantly longer LOS (median 11 vs 7 days; adjusted RR 1.18, 95% CI 1.16–1.21) and fewer DAOH30/DAOH90. Conclusions FUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC.