The C-Reactive Protein May Not Detect Infections Caused by Less-Virulent Organisms.

BACKGROUND: The aim of the present study was to evaluate the influence of organism type on the performance of the synovial fluid C-reactive protein (CRP) test. METHODS: We retrospectively reviewed the results of 21,422 synovial fluid samples sent to one common laboratory for the purpose of diagnostic testing for periprosthetic joint infection. Both a synovial fluid CRP result and a positive culture were present for 1789 submitted samples. The cultured organisms were grouped by species, virulence, and gram type; and the median CRP level was determined for each group. RESULTS: The median synovial fluid CRP level was significantly lower for less-virulent organisms, when compared to those organisms classified as virulent (15.10 mg/L vs 32.70 mg/L; P < .0001). Some less-virulent species such as yeast and Staphylococcus epidermidis were associated with a 4-10 times lower CRP response than those of virulent organisms such as Streptococcus agalactiae and Staphylococcus aureus (P < .0001). Bacterial gram type had no influence on the median CRP result. The rate of false-negative CRP values was 50.9% for yeast, 29.4% for S. epidermidis, 28.5% for all less-virulent organisms, and 11.6% for all virulent organisms. CONCLUSION: The CRP response appears to be highly dependent on the infecting organism and is more likely to provide false-negative results in the setting of less-virulent organisms. Although the use of a CRP level is an important part of the workup for periprosthetic joint infection, surgeons must be aware that this protein may yield a false-negative result in the setting of less-virulent organisms.

The Alpha-defensin Test for Periprosthetic Joint Infection Responds to a Wide Spectrum of Organisms.

BACKGROUND: The alpha-defensin test has been previously demonstrated to be highly accurate in the diagnosis of prosthetic joint infection (PJI), nearly matching the Musculoskeletal Infection Society definition for PJI. However, the relationship between alpha-defensin levels and differing infecting organism has not yet been investigated. QUESTIONS/PURPOSES: The purpose of this study is to describe the breadth of organisms that can trigger a positive synovial fluid alpha-defensin test result in the setting of PJI and also to assess the magnitude of the alpha-defensin result in terms of various pathogen characteristics. METHODS: Between December 2012 and March 2014, one laboratory processed 2319 synovial fluid samples for alpha-defensin testing. The present study reviewed the results of the 1937 samples that simultaneously had a synovial fluid culture performed; these came from 418 surgeons in 42 states. The overall culture-positive rate was 49% (244 of 498) among alpha-defensin-positive synovial fluids and 1% (19 of 1439) among alpha-defensin-negative synovial fluids. The organisms recovered from 244 alpha-defensin-positive, culture-positive fluids were recorded and grouped based on various characteristics, including Gram type, species, virulence, oral pathogenicity, and source joint. Alpha-defensin-negative samples served as uninfected controls. Median alpha-defensin levels were calculated for each group, and Dunn's multiple comparison test for nonparametric data was used to identify any statistically significant (p < 0.05) organism-specific differences in the alpha-defensin level. RESULTS: The alpha-defensin test for PJI was positive in the setting of a wide spectrum of organisms typically causing PJI. The median alpha-defensin level for all 244 alpha-defensin-positive, culture-positive samples (4.7 [interquartile range {IQR}, 3.7-5.3]) was higher than negative controls (0.26 [IQR, 0.22-0.33]) with a median difference of 4.4 (p < 0.001). There were no differences in the median alpha-defensin levels when performing a multiple comparison test among Gram-positive organisms (4.7 [IQR, 3.6-5.3]), Gram-negative organisms (4.8 [IQR, 4.2-5.3]), yeast (4.1 [IQR, 2.2-5.1]), virulent organisms (4.7 [IQR, 3.8-5.2]), less virulent organisms (4.8 [IQR, 3.6-5.4]), oral pathogens (4.5 [IQR, 3.2-5.2]), knees (4.7 [IQR, 3.7-5.3]), hips (4.9 [IQR, 4.1-5.8]), or shoulders (5.3 [IQR, 4.0-10.7]) with all comparisons having a p > 0.999. CONCLUSIONS: The alpha-defensin test provides consistent results regardless of the organism type, Gram type, species, or virulence of the organism and should be seriously considered to be a standard diagnostic tool in the evaluation for PJI. Future research should focus on the performance of this test in specific clinical scenarios such as the immediate postoperative period in the setting of severe immunocompromise and in the setting of a native joint. LEVEL OF EVIDENCE: Level III, diagnostic study.

Mitigating Concerns Over Transport Delays: An Analysis of Synovial Fluid Culture Results in Arthroplasty.

INTRODUCTION:  There is a concern in the field of arthroplasty that synovial fluid transport delays may reduce the accuracy of synovial fluid culture. However, synovial fluid samples collected in the office, and sometimes in a hospital setting, often require transport to a third-party central or specialty laboratory, causing delays in the initiation of culture incubation. This study investigated the impact of transportation delays on synovial fluid culture results. METHODS:  A retrospective review of prospectively collected data at one clinical laboratory, from 2016 to 2022, was conducted. A total of 125,270 synovial fluid samples from knee arthroplasties, from 2,858 different US institutions, were transported to a single clinical laboratory for diagnostic testing including synovial fluid culture (blood culture bottles). Synovial fluid to be cultured was transported in red top tubes without additives. Samples were grouped into six-time cohorts based on the number of days between aspiration and culture initiation (1-day-delay to 6-day-delay). Metrics such as culture positivity, false-positive culture rate, culture sensitivity, and proportional growth of top genera of organisms were assessed across the cohorts. RESULTS:  Of the 125,270 samples in this study, 71.2% were received the day after aspiration (1-day-delay), with an exponential decrease in samples received on each subsequent day. Culture-positive rates for synovial fluid samples received after 1, 2, 3, 4, 5, and 6 days of transport time were 12.2%, 13.3%, 13.5%, 13.1%, 11.6%, and 11.0%, respectively. The maximum absolute difference in culture-positive rate compared to the 1-day-delay cohort was an increase of 1.3% in the 3-day-delay cohort, which was not considered a clinically meaningful difference. The estimated false-positive culture rate remained relatively consistent across time cohorts, with values of 0.3%, 0.4%, 0.3%, 0.2%, 0.5%, and 0.5% for 1, 2, 3, 4, 5, and 6 days of transport time, respectively. None of the cohorts showed a statistically significant difference after adjustment for multiplicity compared to the 1-day-delay cohort. Culture sensitivity was estimated at 68.2%, 67.2%, 70.5%, 70.7%, 65.9%, and 70.7% for 1, 2, 3, 4, 5, and 6 days of transport time, respectively. None of the cohorts showed a statistically significant difference after adjustment for multiplicity compared to the 1-day-delay cohort. Organism proportions were consistent across time cohorts, with Staphylococcus being the most commonly identified organism. No statistically significant differences were found in the proportional contribution of major genera across the cohorts. CONCLUSIONS:  Synovial fluid culture exhibited surprisingly consistent results despite variable transport time to the destination laboratory, with differences that have minimal clinical importance. While the authors of this study advocate for short transport times as a best practice to expedite diagnosis, it appears that concerns regarding the rapid degradation of culture results due to synovial fluid transportation is unwarranted.