What’s New in Musculoskeletal Infection

Periprosthetic Joint Infection (PJI) Introduction PJI is one of the most challenging complications following total joint arthroplasty (TJA), with substantial consequences for physical function, quality of life, mortality, and health-care systems. A large prospective study showed that patients experience significant functional improvement by 12 months after PJI treatment (p < 0.001), but this improvement often plateaus thereafter, particularly in patients with chronic or late-acute infections1. Another study confirmed that physical health, measured by the Short Form-12 version 2 Physical Component Summary (PCS) score, remained below the age-adjusted population norm (mean, 50) even at 24 months, with only 40% of patients achieving a good functional outcome (PCS > 50 or an improvement of ≥8.9 points) despite a clinical cure2. The psychological burden of PJI is also substantial. A large, registry-based study demonstrated that patients undergoing revision for infection, especially women and those with septic revisions, were significantly (p < 0.001) more likely to require psychological support compared with those undergoing primary TJA or aseptic revision3. Moreover, the risk of mortality has been shown to be markedly elevated following PJI. A national cohort study found that PJI after total hip arthroplasty (THA) was associated with a 5.5-fold increase in 10-year mortality at 11.2% compared with matched controls at 2.2% (hazard ratio [HR], 5.49 [95% confidence interval (CI), 3.32 to 9.09])4. Similarly, patients who underwent revision for infection had a higher mortality risk than patients who underwent revision for aseptic indications5, and mortality was even greater when PJI coexisted with infective endocarditis6. Host factors, such as diabetes and the burden of comorbid diseases, contribute to poor outcomes. In a study of patients with chronic PJI, the rate of bacteremia was 15%, and this was independently associated with diabetes and American Society of Anesthesiologists (ASA) classification III, although it did not influence infection-free survival7. In some national U.S. studies, although treatments such as chemotherapy8 were found to increase the risk of PJI, others, such as coronary artery bypass grafting9, did not. Socioeconomic status also influences outcomes: patients with Medicaid insurance undergoing surgery for PJI had significantly higher rates of complications (p = 0.010), readmissions (p = 0.022), and mortality (p = 0.038)10, and those with Medicare Advantage insurance had increased 90-day mortality and complication rates compared with patients with traditional Medicare insurance11. Despite clinical guidelines, evidence shows the underuse of rifampin in staphylococcal PJIs. In a retrospective study, only one-half of the eligible patients were prescribed rifampin, and many discontinuations were undocumented, with drug interactions often cited despite minimal actual risk12. On the microbiological side, registry data have shown that Staphylococcus aureus and coagulase-negative staphylococci were the most common pathogens, but Enterococcus species were associated with higher mortality, emphasizing the need for improved antimicrobial strategies13. From a financial perspective, PJI treatment is a major burden on health-care systems. A multicenter study using activity-based costing estimated the mean hospital cost to be $64,585, with complex 2-stage revisions reaching as high as $369,94814. The hidden workload is also considerable. An analysis of electronic medical record log analysis showed that surgeons and health-care teams spent >8 hours per case on documentation and coordination for patients with PJI, far exceeding that of routine arthroplasty15. The structure and continuity of care also influence outcomes. Patients referred to specialized PJI centers had higher success rates and lower mortality despite having more complex histories16. Conversely, those transferred between institutions mid-treatment had lower success rates and longer interstage intervals and were less likely to proceed to reimplantation17. Finally, registry data confirmed that patients undergoing revision for PJI had significantly higher re-revision rates (adjusted risk ratio [RR], 6.3 [95% CI, 4.0 to 10]; p < 0.001) than those who underwent revision for aseptic causes, although outcomes were better among those managed with debridement, antibiotics, and implant retention (DAIR)18. Prevention Preventing PJI remains a cornerstone of improving outcomes following TJA. Recent literature has highlighted several advancements and clarified misconceptions in the strategies aimed at reducing infection risk. One of the key areas of focus is intraoperative antisepsis. A comparative in vitro study demonstrated that not all antiseptic solutions have equal efficacy in eradicating bacterial biofilms from orthopaedic implant surfaces. The combination of 10% povidone-iodine with hydrogen peroxide showed superior antimicrobial activity across multiple materials commonly used in arthroplasty, whereas other agents such as diluted povidone-iodine and chlorhexidine were less consistent19. This reinforces the importance of selecting antiseptic solutions on the basis of biofilm-targeted effectiveness, particularly in revision cases. The role of wound-closure techniques and postoperative dressing strategies has also gained attention. An international Delphi consensus identified 18 best practices in THA, recommending barbed sutures for faster fascial closure, subcuticular sutures instead of staples to reduce superficial infections, and the use of triclosan-coated sutures to lower surgical site infection risk. Furthermore, negative-pressure wound therapy was endorsed for high-risk patients due to its association with reduced complications and reoperations20. Surgical techniques and technologies have not been shown to increase infection risk. Despite concerns over increased operative time and intraoperative contamination, a large propensity score-matched analysis confirmed that neither computer navigation nor robotic assistance in THA elevated the 90-day PJI risk21. This supports the continued use of these technologies for their known benefits in implant positioning without added infectious complications. Prophylactic antibiotic selection remains crucial. Cefazolin, the standard of care, has been shown to be safe, even in patients with reported penicillin allergies, including those with immunoglobulin E-mediated histories. A large retrospective analysis revealed no significant allergic reactions (0.1% compared with 0.2%; p = 0.480) or increased deep infection rates (0.3% compared with 0.4%; p = 0.680), supporting the broader use of cefazolin without the need for preoperative allergy testing in most cases22. Patient-related factors also play a crucial role in PJI prevention. Obesity, particularly in the presence of comorbidities such as diabetes or chronic kidney disease, significantly increases the long-term risk of infection (HR, 3.4 [95% CI, 1.1 to 10.9]; p = 0.030), with an up to 18% PJI incidence in patients with class-IV obesity and multiple comorbidities23. Likewise, poor nutritional status, as evidenced by low serum albumin levels, has been associated with a higher rate of PJI recurrence, highlighting the need for nutritional optimization prior to surgery24. A history of Clostridium difficile infection was also independently associated with an increased PJI risk, especially when surgery was performed within 6 months after the infection, suggesting that gut dysbiosis and systemic inflammation may compromise host defenses25. Emerging evidence has questioned longstanding practices regarding antibiotic prophylaxis. A retrospective study on dental procedures concluded that antibiotic prophylaxis before dental work does not reduce the risk of late PJI and may be unnecessary26. However, another study indicated that dental diagnoses within 1 year after THA were associated with increased PJI and revision risks, suggesting a need for careful dental management in the perioperative period27. Furthermore, a large, matched-cohort study found that extended oral antibiotic use following THA was associated with a higher, not lower, rate of PJI within 90 days, suggesting that prolonged prophylaxis may be counterproductive28. Collectively, these findings point to a more evidence-based and individualized approach to PJI prevention, balancing surgical technique, antiseptic strategy, patient optimization, and appropriate antibiotic stewardship. Diagnosis The diagnostic landscape of PJI continues to evolve with advancements in biomarkers, imaging technologies, and structured diagnostic pathways. Synovial calprotectin has shown superior diagnostic performance compared with the synovial leukocyte count and polymorphonuclear percentage (PMN%), with an area under the curve (AUC) of 0.96 and a negative predictive value of 100%, establishing it as a powerful rule-out test for chronic PJI29. Synovial C-reactive protein (CRP) also outperformed serum CRP in diagnosing infection and predicting successful reimplantation during 2-stage revisions, with greater sensitivity and prognostic reliability30. The albumin-to-globulin ratio (AGR) and globulin levels have been identified as simple, cost-effective serum biomarkers that demonstrate diagnostic accuracy comparable with or exceeding those of CRP and the erythrocyte sedimentation rate (ESR)31. In parallel, novel blood-based molecular markers, such as CD177, MYBL2, and RRM2, have emerged as potential diagnostic tools with excellent accuracy (AUC, >0.96), showing significant reduction (p < 0.01 for all markers) following successful treatment, and offering a promising noninvasive alternative in cases in which synovial fluid is not accessible32. Neutrophil extracellular trap (NET)-related biomarkers such as cell-free DNA, myeloperoxidase, and citrullinated histone H3 are also significantly elevated in infected synovial fluid (p < 0.01 for all markers) and exhibited high diagnostic power, with cell-free DNA achieving perfect sensitivity and specificity (AUC, 1.0)33. From a screening perspective, D-dimer has demonstrated 100% sensitivity and better specificity than CRP and ESR at a cutoff of ≥244 ng/mL, positioning it as a practical early screening tool34. Preoperative laboratory markers, including the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammation index, have also shown strong predictive associations with PJI, especially in patients with morbid obesity undergoing TJA35. Among imaging techniques, dual-energy computed tomography (DECT) iodine mapping has proven to be a noninvasive and highly accurate modality for differentiating between PJI and aseptic failure. Iodine concentration measurements reached an AUC of 0.964 in the arterial phase and an AUC of 0.970 in the venous phase, outperforming CRP, ESR, and PMN%36. Moreover, microbial diversity analyses revealed that patients with diabetes are disproportionately infected by Candida albicans, Klebsiella pneumoniae, and polymicrobial organisms, highlighting the need for pathogen-specific diagnostic and treatment approaches in this high-risk group37. Regarding reimplantation strategies, a new scoring system based on thresholds for D-dimer, synovial white blood-cell count, and PMN% has been proposed to guide timing. A total score of >2 suggests high reinfection risk, whereas a total score of ≤2 supports safe reimplantation, offering an objective, biomarker-driven decision tool with an AUC of 0.9038. However, diagnostic accuracy can still be undermined by subjective clinical judgment. In a registry-based study, surgeons underreported infection in nearly 20% of true PJI cases, especially those presenting with atypical features such as prolonged wound drainage, underscoring the importance of microbiologic confirmation and multidisciplinary assessment39. A persistent challenge in clinical practice is the “dry tap” during joint aspiration. Notably, 36% of aspirations in a study on THA resulted in dry taps, and 16% of these were later confirmed as PJI. Thus, a dry tap should not be interpreted as reassuring, and further diagnostic workup is essential40. Lastly, a cost-conscious analysis revealed that 96.4% of PJIs could be accurately diagnosed using conventional Musculoskeletal Infection Society (MSIS) criteria alone, without resorting to expensive markers such as synovial alpha-defensin, supporting a stepwise, resource-sensitive diagnostic model41. Surgical Treatment DAIR DAIR remains a widely used approach for managing acute PJIs, particularly in early postoperative and acute hematogenous cases with a well-fixed implant. However, recent evidence has reshaped our understanding of its efficacy, limitations, and adjunct strategies. Large registry studies have provided crucial insight into the long-term outcomes of DAIR. In a study analyzing 5,827 DAIR procedures from the American Joint Replacement the incidence of complications reached at following total arthroplasty and at after Notably, of patients underwent only 1 but those who underwent multiple had markedly the to Similarly, a registry study from DAIR cases found that treatment was significantly associated with (p < 0.001), (p = and higher (p < were better when DAIR was performed within of the arthroplasty, emphasizing the importance of and patient outcomes following successful DAIR have also been One study found although physical were lower in the DAIR and Joint Replacement and were comparable with those of patients who had The success rate was supporting DAIR as a treatment in The use of antibiotic therapy after DAIR has gained as a to infection-free In a multicenter study, antibiotic therapy for a of months resulted in a rate at with minimal and no antibiotic systemic antibiotics, antimicrobial are A study the use of a novel and DAIR. 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