Culture-Negative Periprosthetic Joint Infection

Authors/contributors
Abstract
Negative results on culture still pose a real challenge in the diagnosis of periprosthetic joint infection. There are numerous reasons for the inability to isolate the infecting organism from the affected joint, the most important of which is the administration of antibiotics prior to obtaining culture samples. For patients suspected of having a periprosthetic joint infection, antibiotics should not be given until the diagnosis is confirmed or aspiration of the joint should be delayed for at least two weeks after the last dose of antibiotics. Other strategies that can be used to enhance the likelihood of obtaining a positive result on culture include expeditious transport of culture samples, placement of a tissue or fluid sample in the appropriate medium, implant sonication, and prolonging the incubation period of the samples to two or three weeks. In patients in whom the prerevision aspiration has not yielded an infecting organism, yet the clinical picture is consistent with periprosthetic joint infection, a minimum of three to five tissue culture samples are recommended at the time of revision surgery. Biomarkers and molecular techniques, such as polymerase chain reaction identification of bacterial DNA, may play an increasing role in the future in the diagnosis of periprosthetic joint infection, when standardized techniques have not identified an infecting organism.
Publication
Journal of Bone and Joint Surgery
Date
2014-3-5
Notes

Key findings:

  1. Diagnostic Challenges in PJI: Diagnosis of PJI relies on a combination of detailed history, physical examination, serologic tests, and review of radiographs. The definition by the Musculoskeletal Infection Society emphasizes the diagnostic significance of isolating the same pathogen from two separate tissue or fluid samples obtained from within the joint.
  2. Culture-Negative Infections: In 7% to 12% of cases, cultures are negative despite clear indicators of infection, posing challenges for selecting appropriate antimicrobial therapy. Reasons include prior antibiotic use, failure of traditional culture techniques, and the presence of biofilms that make isolating organisms difficult.
  3. Causes of Culture-Negative Infections: Antibiotic administration prior to obtaining cultures, prolonged wound drainage, and failure of culture techniques (e.g., biofilm encapsulation) contribute to culture-negative cases. Specialized culture mediums, proper sample processing, and transport are crucial.
  4. Strategies to Improve Identification: Recommendations include avoiding antibiotic administration until diagnosis confirmation, obtaining multiple deep joint cultures, using blood culture flasks, delaying joint aspiration post-antibiotic use, and employing proper techniques for sample transfer and transport.
  5. Molecular Techniques: Emerging molecular technologies, such as PCR and biosensors, offer potential for identifying infecting organisms in culture-negative cases. However, their widespread use is still evolving, and validation is needed.
  6. False-Positive Cultures: Recognition of false-positive cultures is crucial. Clean instrument use and proper tissue sample handling can help minimize false positives. Multiple diagnostic tools, including serologic tests, histopathologic examination, and consultation with infectious disease specialists, enhance diagnostic accuracy.

Clinical Implications:

  1. Clinical Approach: In suspected culture-negative cases, repeating joint aspiration, ensuring antibiotic-free periods, and consulting infectious disease specialists are recommended. During revision surgery, obtaining multiple cultures, sonication of retrieved implants, and histopathological analysis aid in confirming the diagnosis.
  2. Overall Recommendations: The American Academy of Orthopaedic Surgeons (AAOS) Clinical Practice Guideline emphasizes preoperative serologic testing, withholding antibiotics, and obtaining multiple intraoperative cultures. Regular communication with the microbiology laboratory and infectious disease specialists is essential.

Strengths:

  1. Expert review
  2. References to field

Limitations:

  1. Review article

Level of evidence: Low (review article)

Citation
1.
Parvizi J, Erkocak OF, Della Valle CJ. Culture-Negative Periprosthetic Joint Infection. Journal of Bone and Joint Surgery. 2014;96(5):430-436.