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Peer-reviewedCC BY 4.0Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

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

Abstract

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 bacteremia (PB) linked to worse outcomes.

Methods: We conducted a cohort study at 2 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 1 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 1 negative FUBC within 48 hours was considered sufficient, 4 patients (1%) without clinical triggers would have been misclassified as EC, potentially missing PB. Potential cost savings from discontinuing FUBCs after 1 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 1 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.

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BibTeX
@article{hendriks2026routine,
  title = {{Routine Serial Follow-up Blood Cultures After a Negative Result Within 48 Hours of Methicillin-susceptible Staphylococcus aureus Bacteremia: Low Yield, High Cost}},
  author = {Marianne M C Hendriks and Eline H H M Kamps and Cairo Norberhuis and Mihai G Netea and Matthijs S Berends and Ianthe Maat and Sander van Assen and Jaap ten Oever and Ilse J E Kouijzer},
  journal = {Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America},
  year = {2026},
  month = jul,
  doi = {10.1093/cid/ciag418},
  url = {https://doi.org/10.1093/cid/ciag418},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Routine Serial Follow-up Blood Cultures After a Negative Result Within 48 Hours of Methicillin-susceptible Staphylococcus aureus Bacteremia: Low Yield, High Cost
AU  - Marianne M C Hendriks
AU  - Eline H H M Kamps
AU  - Cairo Norberhuis
AU  - Mihai G Netea
AU  - Matthijs S Berends
AU  - Ianthe Maat
AU  - Sander van Assen
AU  - Jaap ten Oever
AU  - Ilse J E Kouijzer
PY  - 2026
DA  - 2026/07/15
JO  - Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
DO  - 10.1093/cid/ciag418
UR  - https://doi.org/10.1093/cid/ciag418
AB  - 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 bacteremia (PB) linked to worse outcomes.  Methods: We conducted a cohort study at 2 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 1 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 1 negative FUBC within 48 hours was considered sufficient, 4 patients (1%) without clinical triggers would have been misclassified as EC, potentially missing PB. Potential cost savings from discontinuing FUBCs after 1 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 1 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.
SN  - 1058-4838
SN  - 1537-6591
ER  -