TABLE 1.

Summary of strengths and limitations of strategies used in detection of pathogen and host response

Detection strategy	Strengths	Limitations
Detection of pathogen
Culture-based techniques	Mainstay of pathogen detection in orthopedic infection Increased yield with inoculation of synovial fluid, periprosthetic tissue, and sonicate fluid samples into blood culture bottles Allows for antimicrobial susceptibility profiling of identified organisms Widely available	In setting of PJI, multiple samples required due to low sensitivity of single sample as well as difficulty distinguishing contaminants from true pathogens Yield diminished by presampling antibiotic administration Prolonged incubation required for detection of fastidious organisms
PCR	Facilitates rapid pathogen detection Useful in culture-negative cases where there may have been presampling antibiotic administration Can be used to detect antimicrobial resistance genes	Use of multiplex diagnostic panels will miss atypical pathogens
Shotgun metagenomics	Agnostic pathogen detection Can provide additional information for strain identification, surveillance data, and prediction of antimicrobial resistance	Significant cost Complex associated workflow Technique susceptible to bacterial contamination at multiple steps during processing
Detection of host response
Serum biomarkers	Inexpensive Widely available	Lack specificity in diagnosis of orthopedic infection
Synovial fluid cell count and differential	Quantitative assessment of joint inflammation useful in both native and prosthetic joint infection	Difficult to interpret in setting of inflammatory arthropathies Varies depending on presence of prosthesis, duration of symptoms/time postimplantation/joint involved
Synovial fluid biomarkers	Alpha defensin available as both a lateral flow test (result available within minutes) and an ELISA Alpha defensin higher reported sensitivity compared with CRP, IL-6, and leukocyte esterase	Utility of leukocyte esterase test affected by presence red cells Costly Lateral flow alpha defensin lower sensitivity compared to ELISA
Histology	Can confirm presence inflammation and give further information regarding potential etiology Intraoperative frozen section can aid real-time decision-making regarding surgical approach in setting of revision of prosthetic implants	Sensitivity not high enough to use as a stand-alone “rule out test” for infection
Radiology	Useful in evaluation of noninfective causes of symptoms Can provide supportive evidence for infection May guide invasive diagnostic sampling	Findings often nonspecific