What are the criteria for blood culture in Staphylococcus aureus (S. aureus) infections and when to discontinue antibiotic therapy?

From the Guidelines

Blood cultures should be obtained in all patients with suspected Staphylococcus aureus infections, particularly those with fever, signs of sepsis, endocarditis, device infections, or persistent bacteremia, and antibiotics should be continued until blood cultures are negative and clinical improvement is observed, with specific durations depending on the infection type. When managing Staphylococcus aureus infections, it is crucial to prioritize blood culture collection and appropriate antibiotic therapy to minimize morbidity, mortality, and improve quality of life.

Key Considerations

• Two sets of blood cultures from different sites should be collected before starting antibiotics whenever possible, as recommended by 1.
• For confirmed S. aureus bacteremia, follow-up blood cultures should be drawn every 24-48 hours until clearance is documented, as suggested by 1.
• Antibiotic durations should be tailored to the specific infection type:
  • 14 days for uncomplicated bacteremia,
  • 4-6 weeks for endocarditis or complicated bacteremia (with metastatic foci),
  • and 2-4 weeks for most soft tissue infections after source control, as outlined in 1 and 1.

Antibiotic Selection

• Methicillin-sensitive S. aureus (MSSA) is typically treated with nafcillin, oxacillin, or cefazolin,
• while methicillin-resistant S. aureus (MRSA) requires vancomycin or daptomycin, as recommended by 1 and 1.

Additional Recommendations

• Early infectious disease consultation improves outcomes in S. aureus bacteremia, as emphasized by 1.
• The importance of obtaining blood cultures and appropriate antibiotic duration stems from S. aureus's virulence and ability to cause metastatic infections, with inadequate treatment leading to relapse, endocarditis, and increased mortality, as highlighted in 1 and 1. Based on the most recent and highest quality study, 1, which provides contemporary management guidelines for Staphylococcus aureus bacteremia, the treatment approach should prioritize individualized antimicrobial therapy, early source control, and appropriate antibiotic duration to ensure optimal patient outcomes.

From the FDA Drug Label

The 182 patients with bacteremia comprised 121 with complicated S. aureus bacteremia and 61 with uncomplicated S. aureus bacteremia. Complicated bacteremia was defined as S aureus isolated from blood cultures obtained on at least 2 different calendar days, and/or metastatic foci of infection (deep tissue involvement), and classification of the patient as not having endocarditis according to the modified Duke criteria. Uncomplicated bacteremia was defined as S aureus isolated from blood culture(s) obtained on a single calendar day, no metastatic foci of infection, no infection of prosthetic material, and classification of the patient as not having endocarditis according to the modified Duke criteria

The criteria for blood culture in S. aureus infections include:

• Complicated bacteremia: S aureus isolated from blood cultures obtained on at least 2 different calendar days, and/or metastatic foci of infection, and classification of the patient as not having endocarditis according to the modified Duke criteria
• Uncomplicated bacteremia: S aureus isolated from blood culture(s) obtained on a single calendar day, no metastatic foci of infection, no infection of prosthetic material, and classification of the patient as not having endocarditis according to the modified Duke criteria

As for discontinuing antibiotic therapy, the label does not provide explicit criteria. However, the study treatment duration was based on the investigator's clinical diagnosis, and the final diagnoses and outcome assessments were made by a treatment-blinded Adjudication Committee at the Test of Cure visit (6 weeks after the last treatment dose) 2.

Key points:

• The decision to discontinue antibiotic therapy should be based on clinical judgment and assessment of the patient's response to treatment.
• The label does not provide specific guidance on when to discontinue antibiotic therapy in patients with S. aureus infections.

From the Research

Criteria for Blood Culture in S. aureus Infections

• Blood cultures should be repeated 3 days following initiation of antistaphylococcal antibiotic therapy in all patients with S. aureus bacteremia 3
• Positive blood cultures at 3 days may prove to be a useful marker in promoting more aggressive management, including more potent antibiotic therapy and surgical resection of the valve in endocarditis cases 3
• Patients with S. aureus bacteremia who have community acquisition of infection, underlying valvular heart disease, intravenous drug use, unknown portal of entry, history of prior endocarditis, and possibly, nonwhite race should undergo echocardiography to screen for the presence of endocarditis 3

Discontinuation of Antibiotic Therapy

• The duration of therapy is at least 14 days with uncomplicated SAB, whereby the entire therapy should be carried out intravenously 4
• In case of complicated SAB, a total therapy duration of at least 4-6 weeks is recommended 4, 5
• Additional blood cultures to document sterility are not necessary after 2 follow-up blood culture results are negative in well-appearing patients 6
• Intravenous treatment for at least two weeks up to 4-6 weeks with antistaphylococcal penicillins for MSSA and vancomycin or daptomycin for MRSA bloodstream infection is indicated 5

Management of S. aureus Bacteremia

• A positive blood culture for S. aureus should prompt a thorough patient assessment to identify a potential focus of infection, and the risk factors for the development or presence of complicated infection 7
• Clinical management depends on the patient's characteristics and presenting features 7
• Follow-up blood cultures, source identification, including transoesophageal echocardiography in patients with risk profile, and rapid source control are important measures 4