CORR Insights®: What is the Accuracy of a Rapid Strip Test That Detects D-lactic Acid in Synovial Fluid for the Diagnosis of Periprosthetic Joint Infections?

Where Are We Now?

Periprosthetic joint infection (PJI) is a devastating complication for which effective treatment begins with an accurate diagnosis. Various synovial and serum markers are used for the diagnosis of PJI and are included in the newest definitions of PJI [1-4, 6], but current diagnostic tests and scoring systems have limitations [1-5, 6]. For example, various serum tests take time to complete, and scoring systems require knowledge or memorization of each metric and its range of accepted values. This leads to delays in diagnosis or inaccurate diagnoses. Because of those shortcomings, the diagnosis of PJI would be improved with a specific, sensitive, and easy-to-administer test.

Any such test would be a real boon; PJI is a major social and economic problem with substantial mortality and morbidity, and its impact is likely to grow. One projection suggested that by 2030, one million THA procedures will be performed every 2 years [5]. The number of TKAs is also projected to increase substantially through 2030 [5].

Enter Grzelecki et al. [1] in this issue of Clinical Orthopaedics and Related Research®, who prospectively tested the synovial fluid of 157 patients who underwent revision THA or TKA at one orthopaedic center using a D-lactic acid (DLA) test. The premise for a DLA test is that only bacteria produce DLA, and if DLA is present, then bacteria must be present as well (that is, an infection). The authors concluded that a rapid off-label DLA strip test is valuable for diagnosing PJI, even though it has limitations, such as observer interpretation of the colorimetric aspect of the test and obliteration of the color change by blood. The study by Grzelecki et al. [1] is important for several reasons. First, their work moves clinicians closer toward a specific, real-world practical information test. Moreover, their work provides valuable insight for orthopaedic surgeons and infection researchers regarding current testing options.

Where Do We Need to Go?

In their article, Grzelecki et al. [1] discussed the utility of serum or synovial sample centrifugation before strip testing. Centrifugation permits removal of color contaminating red blood cells. However, there are limitations to centrifugation because of the time lapse between sampling, centrifugation, and strip testing. Therefore, a strip test of centrifugated fluid may not prove to be the best assay for DLA. Improvements such as a redesign of off-label DLA strip tests could also be made. Redesigns in strip tests are the realm of biochemical companies, and on the surface would appear theoretically possible and beneficial to the diagnosis of PJI. Currently it is unknown whether all bacteria produce DLA. Therefore, future improvements in PJI diagnostic sensitivity and specificity will likely depend on structural and physiologic differences between human and bacterial cells.

How Do We Get There?

In the past, we have identified various serum tests unique to infections to aide in diagnosing an infection. These tests include complete blood count, erythrocyte sedimentation rate, and C-reactive protein, among others. Going forward, improved infection diagnosis will likely depend on identifying the unique biophysical properties of bacteria and its biofilm. We now know from Grzelecki et al. [1] that DLA is unique to bacteria, and it can be used for the diagnosis of infection if the colorimetric limitations can be overcome and once we determine whether DLA production is universal across all bacteria.

Regarding improvements in the strip test, first, there could be a redesign to a binary reading on the strip to replace the color change. This could be in the form of a “+” or a “–” illuminated on the strip. Second, we need to determine whether D-lactate is a metabolite for all bacteria. Third, the strip test needs to be free of interference from blood. This is why a reading of “+” or “–” is warranted.

If these strip test improvements do not become available, a remaining area of research would be to study whether bacterial biofilms release metabolites or biomarkers suitable for diagnosing PJI. The results from research on biofilm metabolites could provide valuable information on inhibiting biofilm formation and its contribution to PJIs.

Basic science research is critical to improving the diagnosis and treatment of PJI. For example, in this study, Grzelecki et al. [1] harnessed a fundamental difference in L-lactate and its isomer, D-lactate, production.

Identifying all bacteria that produce DLA could be achieved through multicenter bacteria sampling and testing at centers with numerous infections annually.

Of course, PJI management lies in prevention, more so than in diagnosis and treatment. The opportunities for prevention are many and far beyond the scope of this commentary. Still, I look forward to future work in the realm of PJI diagnosis, and I thank Grzelecki et al. [1] for their work.