CORR Insights^®: Is Treatment With Dithiothreitol More Effective Than Sonication for the Diagnosis of Prosthetic Joint Infection?

Where Are We Now?

In their randomized study, Sambri and colleagues [10] examined the use of dithiothreitol (DTT) and sonication for diagnosing prosthetic joint infections (PJI). The authors conclude that both methods were more sensitive than tissue cultures, and that DTT was superior to sonication in patients where aseptic loosening was suspected from preoperative analyses.

Diagnosing PJI remains a unique challenge for orthopaedists, infectious diseases specialists, and microbiologists, because clinical signs are only inconsistently confirmed by laboratory analysis, especially in chronic infections [7]. Although efforts have been made to improve the sensitivity of PJI diagnosis in the lab, isolating and identifying the pathogen is, I believe, the gold standard for laboratory diagnosis and represents one of the main criteria for defining these infections [9, 14].

Biofilm plays a critical role in both diagnosis and management of PJI. In fact, biofilms affect culture sensitivity, hampering microbial removal from the infected site while also limiting the efficacy of antibiotics. Researchers have tried dislodging microorganisms from biofilm before culture to improve the sensitivity of microbiological diagnosis. Indeed, previous research [12, 13] showed the superiority of sonication over tissue culture. However, sonication is limited by its instrumentation, which is not available nor affordable in all laboratories, and its risk of sample contamination caused by damaged or improperly sealed sample containers [1]. DTT, a sulphydryl compound well known in clinical microbiology for treatment of respiratory samples, is one alternative to sonication. The chemical agent can effectively produce microbial recovery from prosthetic implants and periprosthetic tissues with specificity and sensitivity comparable or even higher than sonication [4, 6]. DTT is easy to use, does not require dedicated tools, and can be applied to both implants and tissues.

Where Do We Need To Go?

Future research should help us to define how to maximize both diagnostic sensitivity and specificity of PJI diagnosis. Several studies have proposed a novel biomarker, specifically designed for diagnosing PJI [8, 11]. However, considering the importance of pathogen identification, new approaches to maximizing the yield we obtain from cultures are needed. Although sensitivity of diagnosis may be increased by analyzing multiple samples, one should consider that contamination may occur through contact with the patient’s skin in the surgery room [2] or in the laboratory, and so specificity will be just as important as sensitivity; we also need to limit the risk of contamination, while also maintaining sensitivity of the diagnosis.

Prolonged cultures have been shown to improve examination sensitivity, increasing the isolation rate of low-grade pathogens, such as coagulase-negative staphylococci and Propionibacteria, some of which are now listed under the genus Cutibacterium [5]. Still, clinicians should make an early diagnosis if possible. Molecular assays provide a quick diagnosis of several infections, but they have not improved the diagnosis times for PJI. Researchers need specific and sensitive molecular assays that can cover a wide range of pathogens.

How Do We Get There?

Laboratories collect and process samples in different ways making it difficult to standardize the microbiological diagnosis of PJIs. A standardized system could limit the risk of contamination. Large population studies should evaluate standard procedures for collecting and processing implants and tissues. Sensitivity of synovial fluids culture is reported to be highly variable, but generally lower than that of other specimens. Laboratory diagnoses could benefit from improved synovial fluid cultures. The recent finding that bacteria form biofilm-like aggregates, which are responsible for recalcitrance to antimicrobial therapy [3], suggests that using treatments that can remove bacteria from biofilm may improve the yield of synovial fluid culture. Unfortunately, we still lack data on this issue. Comparative studies exploring this hypothesis, even on small populations, could help to set up new treatments of synovial fluids.