Year: 2019
Type: article
Abstract: This update on musculoskeletal infection presents a review of infection-related articles from January 2018 through the present from English-language journals, located using the National Center for Biotechnology Information web site, with a special emphasis on periprosthetic infection. The additional sections will cover recent salient articles in the areas of spine, trauma, hand, and pediatrics. In a recent analysis of the Medicare Inpatient Data Set from 2005 to 2015, the risk of periprosthetic joint infection was 1.09% for hips and 1.38% for knees at 5 years. This risk did not change significantly during this 10-year period. Therefore, because the demand for total joint arthroplasty is projected to increase substantially in the coming years, the incidence of periprosthetic joint infection is anticipated to scale up proportionally1. Conversely, the risk of mortality after periprosthetic joint infection decreased significantly during the time frame studied. However, the 5-year survival for Medicare patients was only 67% for periprosthetic infection after total hip arthroplasty and 72% for periprosthetic infection after total knee arthroplasty1. This high mortality rate following periprosthetic infection was echoed in 2 other studies in which the 5-year mortality for patients with periprosthetic joint infection after undergoing total joint arthroplasty was 21.12% for those who underwent total hip arthroplasty2 and 21.64% for those who underwent total knee arthroplasty3. The reported 1-year mortality in these studies had an odds ratio of 3.58 for periprosthetic joint infection after total hip arthroplasty2 and 3.05 for periprosthetic joint infection after total knee arthroplasty3 compared with the national age-adjusted risk of mortality. Included in the cost of health care and, in particular, periprosthetic infection is the cost of litigation. In a retrospective review of medical malpractice lawsuits in a 5-county area in the Northeast United States including 113 total joint surgeons, 27% (31 of 113) were named in at least 1 lawsuit. Infection was the top reason for such litigation, representing 26.5% of all lawsuits4. Prevention Prevention of periprosthetic joint infection has been a topic of considerable interest4-6 with a focus on preoperative, intraoperative, and perioperative considerations. Optimization of patients’ comorbidities is important in the prevention of periprosthetic joint infection. In a meta-analysis study designed to determine the influence of a bariatric surgical procedure prior to arthroplasty, Li et al. found that a bariatric surgical procedure reduced short-term medical complications, length of stay, operative time, and short-term periprosthetic infection in the knees but not the hips. A bariatric surgical procedure did not reduce the long-term risk of infection or complications7. In a retrospective cohort, Castano-Betancourt et al. determined that patients with rheumatoid arthritis or ≥2 other defined comorbidities, such as diabetes and anemia, are at elevated risk for periprosthetic joint infection8. Previous work has demonstrated the importance of long-term glycemic control in the prevention of periprosthetic joint infection9. Recently, there has been interest in glucose control more proximate to a surgical procedure10. Concern has been raised with regard to dexamethasone administration in total joint arthroplasty in patients with diabetes. O’Connell et al. observed an association between dexamethasone administration and a significant increase in early postoperative blood glucose levels in patients with diabetes following total joint arthroplasty and advised that dexamethasone be used with caution in this population11. The association between preoperative dexamethasone and elevated postoperative blood glucose in patients with diabetes was confirmed in a separate study by Godshaw et al.; however, the study did not demonstrate a connection between dexamethasone and postoperative periprosthetic joint infection12. The routine use of adjuvant antibiotic-laden cement in primary total joint arthroplasty has been called into question. In a meta-analysis, King et al. found that the use of antibiotic-laden cement did not reduce the risk of postoperative periprosthetic joint infection compared with regular cement but was associated with a significant increase in cost13. Substantial attention has been dedicated to local irrigation solutions for the prevention of periprosthetic joint infection in primary total joint arthroplasty. In an in vitro study investigating commonly used solutions, Campbell et al. showed that the Dakin solution forms potentially toxic precipitates when mixed with hydrogen peroxide and chlorhexidine gluconate; the authors recommended that surgeons avoid mixing irrigation solutions in the wound during a surgical procedure14. Ernest et al. performed an in-depth, in vitro analysis to assess the efficacy of povidone-iodine, chlorhexidine, hydrogen peroxide, the Dakin solution, and chlorine dioxide in reducing adherent Staphylococcus aureus colonies on common orthopaedic materials. The authors showed that the most effective solutions were hydrogen peroxide, with a 97% reduction in colony-forming units (CFU)/cm2, and povidone-iodine, with a 98% reduction in CFU/cm2. However, these solutions did not eliminate bacteria completely, and the authors recommended continued pursuit of adjuvants to eliminate adherent bacteria during irrigation and debridement for periprosthetic joint infection15. Efficiency and cleanliness in the surgical environment are critical for economic and clinical success in arthroplasty. Two studies demonstrated that prolonged surgical time is associated with the development of infection after total joint arthroplasty16,17. In another study addressing the effect of the operating room environment on periprosthetic joint infection, Vijaysegaran et al. showed that space suits are associated with increased particle and microbiological emission rates in a simulated operating room compared with standard operating room attire, calling into question the safety of routine space suit use during total joint arthroplasty18. Antimicrobial Treatment Oral Antibiotics in Arthroplasty A randomized controlled trial did not show that preoperative doxycycline reduced the prevalence of Cutibacterium acnes (formerly Propionibacterium acnes) on the skin and in the deep tissues at the time of periprosthetic joint implantation19. Debridement, antibiotics, and implant retention followed by chronic oral antibiotic suppression for acute total knee arthroplasty periprosthetic joint infection produced a 5-year infection-free survival of 66% in 1 small single-center study that lacked a control group20. A retrospective cohort study found that oral antibiotic prophylaxis for 7 days after a primary total knee arthroplasty or total hip arthroplasty in patients deemed at high risk for periprosthetic joint infection lowered the risk of periprosthetic joint infection21. However, the authors did not have a control group of high-risk patients and thus recommended the need for further study before widespread adoption of this protocol. Topical Vancomycin Two meta-analyses evaluating the effect of intrawound vancomycin in spinal surgery found that the groups treated with vancomycin had a significantly lower risk of surgical site infection22,23. Two single-center studies demonstrated a lower rate of surgical site infection in patients who underwent primary arthroplasty with the use of intrawound vancomycin powder24,25. However, both studies were retrospective studies with historical controls. One of these studies24 was confounded by the concomitant use of a povidone-iodine solution, and both authors noted the need for further study. One other study demonstrated an increased rate of sterile wound complications in the vancomycin group26. These authors recommended against the use of vancomycin powder, stating that higher-powered studies were needed to demonstrate its efficacy. Animal studies contributed to knowledge regarding the use of topical vancomycin. In a rat model of open contaminated fractures, reduced bacterial growth was observed in both antibiotic bead and vancomycin powder groups when compared with a control group who underwent debridement alone. There were no significant differences between the antibiotic bead and vancomycin powder groups27. In a rabbit model with fixation implants seeded with methicillin-resistant S. aureus (MRSA), the application of intraoperative vancomycin powder at the time of fixation decreased the risk of bone infection and biofilm formation28. Given the retrospective, uncontrolled study designs and conflicting results, the issue of whether topical vancomycin is beneficial in preventing surgical site infection remains unresolved. Antibiotic Complications There were several reports of complications of antibiotic use in orthopaedic patients, including red man syndrome and drug-induced linear immunoglobulin A (IgA) bullous dermatosis after the routine use of vancomycin-loaded bone cement29,30. Acute kidney injury requiring dialysis to lower toxic tobramycin levels after receipt of a vancomycin and tobramycin-impregnated cement spacers has also been reported31. A database review of 83,806 patients who underwent revision total knee arthroplasty due to periprosthetic joint infection found a 1.0% incidence of a Clostridioides difficile (formerly Clostridium difficile) infection after a revision total knee arthroplasty. A diagnosis of C. difficile infection was associated with longer length of stay, higher costs, and greater in-hospital mortality32. Intra-Articular Antibiotics One study assessed local, plasma, and urine concentrations of a gentamicin or vancomycin-loaded mineral composite antibiotic carrier and found a low plasma concentration and high local concentration of both antibiotics. The results also indicated that a deep surgical drain may decrease the amount of antibiotic available for systemic absorption33. A small prospective study evaluated the concentrations of gentamicin and vancomycin from antibiotic-impregnated spacers in 2-stage revision arthroplasty, as well as in vitro. The antibiotic concentration in spacer cement decreased rapidly in vitro within the first 24 hours, but in vivo, antibiotics were present much longer in tissues34. Work on an improved antibiotic delivery system using a layer-by-layer technique to load gentamicin on nanoparticles blended into the powder of bone cement demonstrated longer antimicrobial activity when compared with control cement specimens35. Antibiotic Prophylaxis for Dental Procedures In a survey of antibiotic-prescribing practices of dentists, 39% of respondents identified the presence of a prosthetic joint as a high-risk condition that required antibiotic prophylaxis. The dentists included in the survey reported greater antibiotic use than currently recommended by existing guidelines36. Diagnosis of Periprosthetic Joint Infection Synovial Biomarkers Renz et al.37 reported on a point-of-contact lateral flow test for synovial alpha-defensin that showed a sensitivity of 54% to 84% depending on the criteria defined by 3 different infection organizations. They concluded that, given the limited sensitivity and high specificity, this test should be used as a confirmatory test rather than as a screening test. Gehrke et al. also compared the accuracy of the laboratory-based quantitative enzyme-linked immunosorbent assay (ELISA) alpha-defensin test with the point-of-contact lateral flow test and found no significant difference in the diagnostic accuracy38. They also reported improved results using a similar methodology (n = 223), with a sensitivity of 92.1% and a specificity of 100%. In a systematic review and meta-analysis, Marson et al.39 noted that the point-of-contact lateral flow test had a lower pooled sensitivity (85%) than the laboratory-based alpha-defensin test pooled sensitivity (95%). The authors believed that these lower pooled results for the lateral flow test were only comparable with the leukocyte esterase test and that further study was necessary prior to widespread adaption. The alpha-defensin biomarker has some limitations in certain cases. Stone et al.40 showed that alpha-defensin in combination with synovial C-reactive protein (CRP) had a high sensitivity for a periprosthetic joint infection diagnosis, but had false-positive results in the presence of metallosis or false-negative results in the presence of low-virulence organisms. Another group confirmed that alpha-defensin is prone to false-positive results in the presence of an adverse local tissue reaction41. Molecular Diagnosis and Sonication Technical advances have decreased the cost of the molecular diagnosis of periprosthetic joint infection. Tarabichi et al.42,43 reported on the use of next-generation sequencing to identify pathogens in synovial fluid and tissue. They showed that cultures were positive in only 61% when compared with next-generation sequencing that identified a pathogen in 89.3% of the infected cases. However, next-generation sequencing also identified microbes in 25% of aseptic revisions with negative cultures and in 35.3% of primary total joint arthroplasties. Therefore, despite the increased yield of identifying pathogens in culture-negative cases, the identification of pathogens in what are currently identified as aseptic cases is a source of concern and needs further research. Similarly, Moshirabadi et al.44 reported on the use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques to diagnose periprosthetic joint infection. They compared PCR-RFLP with cultures and found a sensitivity of 97.4% and a specificity of 100% for PCR-RFLP compared with a sensitivity of 31.6% and a specificity of 100% for cultures. In contrast, in another related study using PCR, Fink et al.45 reported limited operative characteristics of PCR in the diagnosis of periprosthetic joint infection, with a limited sensitivity of 55.6% and a specificity of 82%. However, the PCR techniques varied widely between studies, which can alter the number of false positives when standard PCR techniques are used. Another study showed that PCR results may vary depending on the source: synovial fluid compared with tissue or implant sonication. Sonicated fluid had the best diagnostic accuracy46. Reimplantation Criteria The diagnosis of persistent periprosthetic joint infection after the placement of a cement spacer is challenging with minimal tools available to measure it. Kanwar et al.47 reported the potential use of alpha-defensin in combination with Musculoskeletal Infection Society criteria to predict the success of reimplantation. However, in 27 patients who had negative alpha-defensin results prior to reimplantation, 3 (11%) had a recurrent infection within 1 year. Treatment Published research in 2018 continues to clarify the role of each of the 3 major treatment options for periprosthetic joint infection: irrigation and debridement, 2-stage exchange, and 1-stage exchange. Irrigation and Debridement Irrigation and debridement with retention of components continued to show a high failure rate of 57% in a multicenter study for periprosthetic joint infection after total knee arthroplasty at 4 years48. Patients treated with irrigation and debridement with polyethylene exchange for periprosthetic joint infection within 2 weeks of the index arthroplasty had higher success rates (82%) when compared with those treated beyond 2 weeks (50%)49. Two-Stage Exchange It is often assumed that 2-stage treatment is very successful. However, a recent study questioned the validity of that assumption. In a study of 80 patients who underwent a 2-stage procedure, 14 (17.5%) never underwent reimplantation, 24 (30%) had a serious complication, and of the 66 patients with a successful reimplantation, only 48 (73%) remained infection-free50. Additionally, 9 (11%) of 80 patients required a spacer exchange for persistent infection, 3 of whom underwent eventual failure. Spacer exchange due to persistent infection is not uncommon, occurring in 59 of 3,417 patients in another study, one-third of whom became reinfected within 5 years compared with one-fifth of patients without an interim spacer51. Similarly, if a 2-stage hip procedure fails requiring a repeat 2-stage hip procedure, a reinfection rate of 42% (8 of 19) was noted in a series of 19 patients52. The optimal timing for reimplantation following placement of an antibiotic-loaded spacer remains elusive. Predicting which patients are at risk for failed treatment remains difficult. In a study of 205 patients who underwent a 2-stage procedure, 27% (56 of 205) had a recurrent periprosthetic joint infection. Failure was 1.8 to 2.5 times more likely if the preoperative synovial fluid white blood cell count was >60,000, a neutrophil of or an rate of In a review of infected another group noted an success rate at 4 years. 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Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2963583273