Routine Serial Follow-up Blood Cultures After a Negative Result Within 48 Hours of Methicillin-susceptible Staphylococcus aureus Bacteremia: Low Yield, High Cost

BACKGROUND: Follow-up blood cultures (FUBCs) are essential in managing Staphylococcus aureus bacteremia (SAB). Skip phenomenon (SP), intermittent negative cultures despite ongoing bacteremia, occurs in 4-13% of SAB patients and may lead to premature cessation of diagnostics and inappropriate treatment. Early SP, defined as negative FUBCs within 48 hours after index culture followed by subsequent positivity, is poorly characterized but concerning, as it can mask persistent bacteraemia (PB) linked to worse outcomes. METHODS: We conducted a cohort study at two Dutch hospitals, including adult SAB patients. Patients were categorized as having early clearance (EC), PB, or SP. Primary outcome was early SP prevalence, secondary outcomes included the proportion of potentially missed cases of PB when relying on one negative FUBC within 48 hours, reasons for obtaining FUBCs in early SP patients, and estimated costs of unnecessary FUBCs. RESULTS: Among 1005 included SAB patients, 31 patients had early SP (3.1%). In 27 of these (87%), clinical condition prompted repeat FUBCs. If one negative FUBC within 48 hours was considered sufficient, four patients (1%) without clinical triggers would have been misclassified as EC, potentially missing PB. Potential cost savings from discontinuing FUBCs after one negative result within 48 hours were 13,513 USD per 100 patients. CONCLUSIONS: Early SP in SAB was uncommon. Clinically stable, afebrile patients without signs of metastatic infection and one negative FUBC within 48 hours have a very low risk of missed PB. A day-2-focused, clinically guided approach may reduce low-yield testing and costs, while maintaining patient safety.