Staph Aureus Bacteremia

Staphylococcus aureus (S. aureus) is one of the leading pathogens causing community-acquired and hospital-acquired bloodstream infections ranking second after Escherichia coli. Hospital mortality is high, ranging between 15 and 40%.

In 8–15% of the patients, hematogenous spread may also lead to later secondary complications such as endocarditis, vertebral osteomyelitis, abscesses, and implant associated infections of prosthetic joints, electronic cardiac devices etc., which can occur up to weeks or months after the primary infection. Notably, patients with community-acquired SA-BSI and patients with prolonged bacteremia have an increased risk for secondary foci.

Diagnosis

Through blood cultures which are drawn from the patient based on clinical context initially. Note: urine cultures positive for SA should be treated empirically as SAB until proven otherwise (due to high risk of hematogenous spread). An exception are patients with urinary tract foreign bodies and/or after urological interventions.

Most frequent sources of SA-BSI are intravascular catheters and soft tissue infections

Echocardiography

Endocarditis occurs in about 10–20% of patients with SA-BSI and worsens the patient's prognosis.

1. Start with a TTE on all patients. Identification of a vegetation on TTE usually obviates the need for TEE. However, a negative TTE is not conclusive as TTE is not sufficient for ruling out infective endocarditis.
2. Generally patients w/o obvious vegetation on TTE will also need a TEE. The diagnostic sensitivity of TEE is twice as high as the one of a TTE and should thus be used preferably. The exact indications are controversial.
   1. Potential indications for TEE after a negative TTE:
      1. Prosthetic valve / pacemaker
      2. predisposing valvular abnormality
      3. Presence of peripheral stigmata for IE
      4. Intravenous drug use
      5. Unknown duration of bacteremia (ie, community-acquired infection)
      6. Absence of evident removable source of bacteremia
      7. Hemodialysis dependency
      8. Short time to blood culture positivity (ie, within 24 to 48 hours rather than at later time points)
      9. Persistent S. aureus bacteremia despite appropriate antimicrobial therapy
      10. New heart failure
   2. Potential situations in which one might forgoe TEE with a negative TTE:
      1. Nosocomial or health care-associated acquisition of bacteremia
      2. Sterile follow-up blood cultures within four days after the initial positive culture
      3. No permanent intracardiac device
      4. No hemodialysis dependence
      5. No clinical signs of endocarditis or secondary foci of infection
      6. Removable focus of infection removed promptly, if present
      7. Defervescence within 72 hours of initial positive blood culture

There are some scoring systems for the risk of IE with SAB: VIRSTA is the most validated. Consider TEE for VIRSTA ≥3.

See Infective Endocarditis.

Further Imaging

Consider bone scan, MRI, US/joint aspirate. In particular, if your centre can support it, consider FDG-PET CT if repeat blood cultures are positive due to a very high sensitivity/specificity of finding septic embolic complications compared to conventional diagnostic methods.

Followup and Assessment

• repeat blood cultures q24 hours x 72 hours until documented clearance of bacteremia
• identify and control the source of bacteremia
  • intravascular devices and catheters
  • implanted hardware
  • osteomyelitis (don't forget vertebral/sternoclavicular) and disciitis
  • deep abscesses
• identify and control metastatic infective complications

Treatment

Antibiotic Therapy

• Dual-coverage initially: Mortality rates in patients with methicillin-susceptible Staphylococcus aureus (MSSA) infection are higher if treated with vancomycin instead of an appropriate ß-lactam. However, if the isolate is methicillin resistant (MRSA), appropriate antibiotic cover with vancomycin is required from outset.
  • It is therefore suggested that dual therapy be commenced empirically, reducing therapy to a single agent when sensitivities are determined (usually within 48 hours after initial isolation).
• Cefazolin vs anti-staph PCN:
  • cefazolin is not inferior to a therapy with anti-staphylococcal penicillins in the therapy of MSSA bloodstream infections
  • cefazolin treatment was associated with a significant lower risk for drug side effects (nephrotoxicity, hepatotoxicity, venous irritation)
• Other beta-lactams
  • Piperacillin/tazobactam, ceftriaxon, cefuroxim and other broad spectrum beta-lactams should not be used for definite treatment of SA-BSI despite in vitro confirmed susceptibility, because they are not only associated with a higher likelihood to select multi-drug resistant pathogens but also with an increased mortality according to retrospective studies

MRSA

• First-line: vancomycin (target trough 15–20 mg/L )
• Second-line: daptomycin (8–12 mg/kg ideal bodyweight)
• Linezolid should not be used for MRSA bloodstream infection due to its bacteriostatic effect
• The new MRSA effective cephalosporins (ceftarolin, ceftobiprole) and lipoglycopeptides (dalbavancin) should not yet be used as first choice as there are no randomized controlled trials in patients with MRSA bloodstream infections

Combination Therapy

There is no role for routine combination therapy of antistaphylococcal penicillins or vancomycin with aminoglycosides, rifampin, or daptomycin for treatment of staphylococcal bacteremia

Duration of Treatment

• Uncomplicated bacteremia: 2 weeks
• Complicated bacteremia without endocarditis or osteomyelitis: at least 4 weeks
• Complicated bacteremia with endocarditis: at least 6 weeks
• Complicated bacteremia with osteomyelitis: at least 8 weeks

repeat blood cultures 2 – 4 days are negative, AND defervesce within 72 hours of therapy.

Followup

• Patients should be reassessed 4 weeks following completion of antibiotic therapy due to the risk of relapse.

References

1. Management of Staphylococcus aureus bacteremia in adults | CMAJ
2. Clinical approach to Staphylococcus aureus bacteremia in adults - UpToDate
3. Staphylococcus aureus Bacteremia - IDSA Guidelines - IN DEVELOPMENT
4. Clinical Management of Staphylococcus aureus Bacteremia: A Review | Critical Care Medicine | JAMA | JAMA Network
5. https://www.sahealth.sa.gov.au/wps/wcm/connect/450f0b80469722d7b4bdf6b0ec6dccc9/Guideline_SAB+Management_v1.2_18.07.2019.pdf?MOD=AJPERES&CACHEID=ROOTWORKSPACE-450f0b80469722d7b4bdf6b0ec6dccc9-oe7bbpR
6. Frontiers | Management of Staphylococcus aureus Bloodstream Infections