What’s New in Musculoskeletal Infection (2020)

This update on musculoskeletal infection presents a review of infection-related articles from January 2019 through April 2020, in English-language journals, located using the National Center for Biotechnology Information website, with a special emphasis on periprosthetic joint infection (PJI). The additional sections cover recent salient articles in the areas of spine, trauma, hand, and pediatrics. Overview While PJI remains a devastating complication for patient and surgeon alike, progress in diminishing its prevalence may be occurring through preoperative optimization, intraoperative strategies, and postoperative wound therapy. In a recent study using data from the National Surgical Quality Improvement Program (NSQIP), the authors evaluated the incidence of surgical site infections (SSIs) in the first 30 days following total hip arthroplasty (THA) in 2016 compared with the years 2012 to 20151. The greatest incidence of combined superficial and deep SSI was in 2012 (1.12%), while the lowest incidence was in 2016 (0.81%), a 28% decrease (p < 0.01). However, the incidence of deep infection was not significantly different between 2012 (0.30%) and 2016 (0.23%) (p = 0.153). Interpretation of these data must be tempered by the fact that they only reflect 30-day outcomes. Mortality following PJI remains a serious issue. A systematic review of 19,169 patients with an average age of 65 years noted a 5-year mortality rate of 21%. The 1-year mortality risk was significantly higher than that for an aged-matched group of U.S. citizens (p < 0.001; odds ratio [OR], 3.58)2. Treating patients with PJI is resource-intensive, requiring longer hospital stays and multidisciplinary treatment to ensure optimal results. An NSQIP database study compared resource utilization between 16,006 septic revision cases and 11,951 aseptic revisions. The authors found a significantly greater length of stay and rate of readmission, reoperation, and complications in the septic revision group (p < 0.001). As such, health policy-makers need to risk-adjust prospective payments to prevent the creation of disincentives to treat infected patients3. Defining a successful result following the treatment of PJI remains elusive. In order to clarify this, the Musculoskeletal Infection Society (MSIS) convened a group to help define successful PJI treatment. They proposed a tiered system, with Tier 1 being infection control; Tier 2, infection control with suppressive antibiotics; Tier 3, need for reoperation and/or revision; and Tier 4, death. Use of this system will provide consistency in reporting and help to determine whether failure is directly or indirectly related to PJI4. Prevention The prevention of PJI after total joint arthroplasty (TJA) was a research topic of considerable interest in 2019. Articles generally focused on preoperative and intraoperative factors that affect PJI5. Several studies focused on the optimization of medical conditions prior to surgery to minimize infection risk. Two separate meta-analyses demonstrated a correlation of malnutrition with increased wound-healing and infection after arthroplasty (OR of 2.17 and 2.49 in the 2 studies, respectively)6,7. Prospective research will be required to determine whether correction of malnutrition normalizes PJI risk. Bedard and colleagues showed an increase in postoperative wound complications (OR, 1.78) and PJI (OR, 2.02) after TJA among tobacco users compared with nonusers in a meta-analysis of 14 studies8. In a study analyzing the data of U.S. veterans with hepatitis C in the TJA setting, it was shown that preoperative treatment of hepatitis C reduced the risk of postoperative infection roughly 2 to 3-fold after TJA9. Perioperative antibiotic use is a powerful strategy for the prevention of PJI. In a retrospective study of 20,682 primary TJAs, the authors demonstrated through regression analysis that a single dose of preoperative intravenous (IV) antibiotics is as effective as 24 hours of perioperative dosing in the prevention of postoperative PJI10. Two other studies showed no benefit from the use of commercially available antibiotic-impregnated bone cement for total knee arthroplasty (TKA)11,12. Regarding local reduction of bacterial burden, Letzelter et al. presented a thorough review of different skin preparation solutions commonly utilized in orthopaedic surgery. They concluded that no consensus exists and that each area of the body may have its own microbiome, which may display different responses to the same skin antiseptic solution13. Goodman and colleagues demonstrated a higher prevalence of nasal methicillin-resistant Staphylococcus aureus (MRSA) carriage among patients with rheumatoid arthritis compared with controls, suggesting a possible explanation for higher infection rates postoperatively14. Substantial effort has been dedicated to studying the effect of the operative environment on PJI. Results from the Mayo Clinic database called into question the idea that intraoperative dilute povidone-iodine irrigation is protective against PJI in both primary and revision TJA. In analyses of 11,738 primary and 2,884 revision cases, the authors found no difference in the rate of reoperation for infection at 3 and 12 months, comparing cases performed with and without the use of dilute povidone-iodine15,16. In a small-scale pilot study, Cook et al. showed a significant reduction in postoperative infection after primary TJA performed in an operating room with a supplemental ultraviolet-light-based air decontamination system17. In an observational study, Klaber et al. showed a low overall rate of bacterial contamination of surgical gowns during hip arthroplasty procedures, provided the operative time was <120 minutes, highlighting the importance of efficiency in the operating room18. Surgical and patient factors have also been studied in relation to PJI after TJA. Taneja and colleagues showed that patients who received an allogeneic blood transfusion had a higher PJI risk compared with those who were not transfused19. Prolonged duration of surgery in primary TJA was shown to be associated with increased risk of PJI20, with a separate study showing an 18% increase in PJI for every 15 additional minutes in the operating room for primary TKA21. In a prospective randomized controlled trial, Newman and colleagues showed that patients undergoing revision TJA whose wounds were dressed with a negative-pressure device had a lower 12-week reoperation rate than those whose wounds were dressed with a standard dressing22. Keeney et al. showed similar early benefits in primary TJA dressed with a negative-pressure device, but there was no difference in longer-term PJI risk23. Diagnosis of PJI Shohat et al. validated an algorithm for diagnosing PJI using defined diagnostic criteria24; they defined PJI cases using only major MSIS criteria25 (n = 684) and, as a control, used aseptic revision cases that did not demonstrate failure for any reason within 2 years (n = 820). The algorithm was validated using a separate cohort (n = 422), showing a sensitivity of 97% and specificity of 99.5%. Unfortunately, the diagnosis of PJI within 6 weeks of the index arthroplasty is still elusive, as current accepted thresholds for synovial cell count and inflammatory markers have low sensitivity (<60%), especially in coagulase-negative Staphylococcus cases26. Likewise, Lazarides et al. showed that using inflammatory markers to diagnose PJI is not suitable for immunosuppressed patients, and newly described thresholds for synovial cell count and differential have better operative characteristics27. Moreover, Saleh et al. described how the evidence that has been used to set some of the diagnostic criteria is poor at best if analyzed using a validated Quality Assessment of Diagnostic Accuracy Studies tool, calling for better design in future studies28. Joint Aspiration Li et al. described a method to increase culture-positive yield when ≤1 mL of synovial fluid is aspirated: use of saline solution lavage (10 mL) and reaspiration of the joint. The samples were sent in 2 blood culture bottles for inoculation for 14 days in a BACT/ALERT 3D blood culture system (BioMérieux). The authors reported a sensitivity of 80% and specificity of 96%29. Likewise, measurement of synovial fluid viscosity may be a promising test to aid in PJI diagnosis, as it outperformed C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR), with a sensitivity of 93.3% and a specificity of 66.7%30. Serum Biomarkers D-dimer use for PJI diagnosis is still controversial, as Xu et al. demonstrated in a retrospective study. They found that CRP level, ESR, and interleukin (IL)-6 were diagnostically superior to D-dimer. Using an optimized threshold of 1.02 mg/L, the sensitivity of D-dimer was only 68%31. Synovial Biomarkers The alpha-defensin (AD) test continues to demonstrate diagnostic utility in particular scenarios. Among immunosuppressed patients, it demonstrated a sensitivity of 93% and a specificity of 100% in a retrospective study32. However, its use in reimplantation cases demonstrated low sensitivity33. Additionally, using Delphi-based criteria, at 1 year of follow-up34, 19.5% of the cases that had negative results prior to the second stage demonstrated treatment failure. Kleiss et al. also showed that the routine use of AD to evaluate painful hips or knees after arthroplasty is insufficient to accurately diagnose PJI, particularly in low-virulence infections35. However, the leukocyte esterase (LE) test was reported to be useful even in patients who were using antibiotics at the time of aspiration (sensitivity of 78%)36. Additionally, another study showed that the LE assay is better than or equivalent to frozen section histology (sensitivity and specificity of 100% and 93.8%, respectively, compared with 78.3% and 96.9%)37. Molecular Diagnosis Torchia et al. did a cost-effectiveness analysis of the use of next-generation sequencing and concluded that such a test should be reserved for clinical contexts with a high pretest probability of PJI38. In a multicenter study, polymerase chain reaction assay using restriction fragment length polymorphism to detect bacteria demonstrated a sensitivity and specificity of 97.4% and 100%, respectively39. Imaging The diagnostic accuracy of preoperative computed tomography (CT)-guided hip aspiration showed a sensitivity of 66.7% and a specificity of 98%40. Enlarged iliac lymph nodes and aspirated fluid volume of >1 mL were strong predictors of infection. Treatment Published research in the period of this review continued to clarify the role of each of the 3 major treatment options for PJI: irrigation and debridement, 2-stage exchange, and 1-stage exchange. Irrigation and Debridement Irrigation and debridement with component retention continues to show high failure rates (56%) even in the acute hematogenous setting with <3 weeks of symptoms41. A study looking at a 2-stage debridement protocol with component retention in 83 patients showed an 86.7% success rate of infection control with an average follow-up of 41 months42. This shows considerable improvement when compared with previously reported results of single-stage debridement with component retention. The reported success rates for 2-stage exchange following a failed irrigation and debridement procedure remain variable. In a series of 291 knees with an average follow-up of 6.2 years, the success rate was 81% (51 of 63) in the direct staged revision group and 72% (159 of 221) in the failed irrigation and debridement group43. Two-Stage Exchange Recent studies have called into question the success rates of 2-stage exchange. A lack of infection control may lead to the need for an interim spacer exchange for a number of patients, with a rate of 16.9% (90 of 533) seen in 1 recent study44. Some patients may never undergo the second stage; a separate study found that to 18% (111 of 616) did not undergo reimplantation45. These groups of patients traditionally show higher rates of treatment failure and poor outcomes. Polymicrobial and fungal infections remain challenging to treat, with higher failure rates. In a recent study, polymicrobial infections were associated with lower treatment success, increased operative times, and longer hospitalizations when compared with single-organism infections46. In another study, fungal PJI resulted in a 61.5% failure rate with 2-stage exchange at an average of 33 months of follow-up47. The results of a repeat 2-stage exchange for the treatment of recurrent knee infection was found to be largely dependent on MSIS grade, soft-tissue status, and the presence of an antibiotic-sensitive organism48. In this series, all MSIS type-C hosts became reinfected. Different spacer types were examined in numerous studies. Articulating antibiotic spacers remain the standard for the interim treatment of PJI. However, static spacers showed comparable success rates in situations of severe bone loss, with an infection-eradication rate of 77%49. Primary TKA components with high-dose antibiotics are becoming increasingly popular for interim treatment. A multicenter study looking at these spacer types for definitive treatment showed a high rate of success, at 78.9% with minimum 2-year follow-up50. In 1 study, the addition of intramedullary dowels to antibiotic spacer constructs did not enhance infection eradication, despite their common use51. One-Stage Exchange While a prospective multicenter randomized study comparing 1-stage and 2-stage exchange is ongoing in the U.S., results are not yet available. However, 1-stage exchange continues to gain enthusiasm as treatment for PJI. A recent study examined 111 patients undergoing single-stage revision with cementless components for the treatment of chronic infection following THA. Ninety-nine (89.2%) of the patients were infection-free at a mean follow-up of 58 months52. Another study showed a 10-year rate of infection-free survival of 94% following 1-stage exchange for chronic PJI of the hip53. Which patients are good candidates for 1-stage exchange remains a question. In a study including 91 patients who had infection recurrence following 1-stage exchange TKA, risk factors for failure were identified. The authors found that a previous 1 or 2-stage exchange due to PJI and the isolation of Enterococcus or Streptococcus bacteria were associated with a higher risk of failure with 1-stage exchange54. Antimicrobial Treatment Vancomycin Powder The use of vancomycin powder in various surgical procedures remains controversial. Two systematic reviews involving prophylactic vancomycin powder use in spine surgery demonstrated that the use of intrawound vancomycin powder significantly reduced the relative risk of developing a surgical site infection; there was significant among the studies Several other studies demonstrated in deep and superficial with the use of intrawound vancomycin in spine should be 1 meta-analysis found that spine patients who received intrawound vancomycin had but were as to a or polymicrobial SSI compared with patients in the control and other studies demonstrated similar A study using a of found that local of vancomycin may have an effect on Two systematic reviews and meta-analyses of intrawound vancomycin in surgery as as primary and revision demonstrated rates of both studies that only evidence They both concluded of this prospective randomized are in Primary and A retrospective study and meta-analysis evaluated the clinical importance of a culture at reimplantation in 2-stage exchange data of studies showed a higher risk of failure among patients with a culture (OR, weeks of antibiotic treatment following reimplantation the odds of the risk of 3 higher for patients with a culture at reimplantation than for patients with a negative The did not the during reimplantation in of the study was also in the antibiotic and duration as as in the for 2-stage exchange, A randomized controlled evaluated antibiotics for the of bone and joint infections and demonstrated that antibiotic was to for the treatment of bone and joint The results of this study the of bone and joint infections using antibiotics and may result in a of clinical The utility of an period prior to reimplantation in 2-stage exchange arthroplasty was evaluated in a study, which demonstrated a higher rate in patients at 1 who did not antibiotics prior to reimplantation compared with those at another who antibiotics for 2 However, the may reflect a of treatment than antibiotic of the data A study evaluated perioperative antibiotic for patients undergoing TJA. 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