What is the recommended treatment for a surgical site infection with a negative prosthesis culture?

Management of Culture-Negative Prosthetic Joint Infections

For culture-negative prosthetic joint infections, empiric broad-spectrum antibiotic therapy with vancomycin plus a gram-negative agent (such as cefepime or a carbapenem) is recommended, along with appropriate surgical intervention based on infection chronicity and prosthesis stability.

Diagnostic Approach for Culture-Negative PJI

• Obtain multiple tissue samples (3-5) during surgical debridement or prosthesis removal 1
• Consider advanced diagnostic techniques when standard cultures are negative:
  • Sonication of removed implants to dislodge biofilm organisms
  • Extended culture techniques for fungi and acid-fast bacilli
  • Molecular diagnostic methods (16S rRNA PCR) 2
• Evaluate inflammatory markers (ESR, CRP) to monitor treatment response 2, 1

Surgical Management Options

The surgical approach depends on several key factors:

For Early Infections (<30 days post-op) or Acute Hematogenous Infections:

• Debridement, Antibiotics, and Implant Retention (DAIR) if:
  • Well-fixed prosthesis
  • Short duration of symptoms (<3 weeks)
  • No sinus tract
  • Susceptible pathogens (if identified) 2

For Chronic Infections:

• Two-stage exchange (preferred for culture-negative PJI):

  1. Remove infected prosthesis and cement
  2. Place antibiotic-impregnated cement spacer
  3. Administer 4-6 weeks of broad-spectrum antibiotics
  4. Reimplant new prosthesis after infection control 2

• One-stage exchange may be considered in select cases with:

  • Good soft tissue
  • No sinus tract
  • Non-immunocompromised host 2

Empiric Antibiotic Therapy for Culture-Negative PJI

Initial Empiric Regimen:

• Vancomycin (15-20 mg/kg IV every 8-12h, not exceeding 2g per dose) for gram-positive coverage, particularly MRSA 2
• PLUS one of the following for gram-negative coverage:
  • Cefepime 2g IV every 8h 2
  • OR Carbapenem (meropenem or ertapenem) 2, 3

Duration of Therapy:

• 4-6 weeks of IV antibiotics for most cases 2
• Consider longer duration (3 months for hip PJI, 6 months for knee PJI) for staphylococcal infections 1

Special Considerations

For Prosthesis Retention (DAIR):

• Success rates are lower with:
  • Presence of sinus tract (2.84 times higher risk of failure)
  • Symptoms duration ≥8 days before debridement (1.77 times higher risk of failure) 4
• Consider adding rifampin (600mg daily) for suspected staphylococcal infections 2, 1

For Two-Stage Exchange:

• Some experts recommend continuing antibiotics after reimplantation to prevent reinfection 2
• Consider delaying reimplantation for at least 6 weeks, especially for suspected gram-negative infections 2

Monitoring and Follow-up

• Regular clinical assessment for signs of persistent infection
• Serial inflammatory markers (ESR, CRP)
• Radiographic evaluation for evidence of implant loosening or osteolysis 2

Common Pitfalls to Avoid

1. Administering antibiotics before obtaining cultures - compromises microbiological diagnosis 1
2. Inadequate number of tissue samples - increases risk of false negatives 1
3. Failure to consider unusual pathogens (fungi, mycobacteria) in culture-negative cases 2
4. Premature reimplantation before adequate infection control 2
5. Underestimating the role of biofilm - mature biofilms (>4 weeks) typically require implant removal for cure 2

By following this structured approach to culture-negative prosthetic joint infections, clinicians can optimize outcomes while minimizing morbidity and mortality associated with these challenging infections.