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Two-stage treatment of periprosthetic joint infections involves placement of high-dose antibiotic-loaded cement spacers (ACSs). Reports of ACS-induced nephrotoxicity have raised concern regarding systemic absorption of antibiotics after ACS placement. We sought to characterize the serum concentrations of antibiotics that occur after ACS placement.We performed a prospective study of patients with an infected primary total hip (THA) or knee arthroplasty (TKA) treated with standardized ACSs with vancomycin, gentamicin, and tobramycin. Serum antibiotic levels were collected weekly for 8 weeks.Twenty-one patients (10 THA, 11 TKA) were included. Mean serum gentamicin levels ranged between 0.275±0.046 and 0.364±0.163 mg/L; mean serum tobramycin levels ranged from 0.313±0.207 to 0.527±0.424 mg/L; and mean serum vancomycin levels ranged from 5.46±6.6 to 15.34±9.6 mg/L. Serum antibiotic levels were detectable throughout the 8-week duration of ACS treatment. Regression analysis found that diabetes (coefficient 6.73, 95% CI 0.92-12.54, P.05), blood urea nitrogen (coefficient 0.83, 95% CI 0.45-1.22, P.001), number of cement doses (coefficient 3.71, 95% CI 0.76-6.66, P .05), and use of systemic vancomycin (coefficient 6.24, 95% CI 2.72-9.75, P.001) correlated with serum vancomycin levels. Patient age (coefficient -0.01, 95% CI -0.02 to 0, P.01) and male sex (coefficient 0.20, 95% CI 0-0.41, P.05) correlated with serum aminoglycoside level.Systemic absorption of antibiotics from high-dose ACS persists for at least 8 weeks. Patients should be monitored closely for complications related to systemic absorption of antibiotics from ACS treatment.

BACKGROUND Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss and the need for transfusions when administered intravenously in total hip arthroplasty. Oral formulations of the drug are available at a fraction of the cost of the intravenous preparation. The purpose of this randomized controlled trial was to determine if oral and intravenous formulations of tranexamic acid have equivalent blood-sparing properties. METHODS In this double-blinded trial, 89 patients undergoing primary total hip arthroplasty were randomized to receive 1.95 g of tranexamic acid orally 2 hours preoperatively or a 1-g tranexamic acid intravenous bolus in the operating room prior to incision; 6 patients were eventually excluded for protocol deviations, leaving 83 patients available for study. The primary outcome was the reduction of hemoglobin concentration. Power analysis determined that 28 patients were required in each group with a ±1.0 g/dL hemoglobin equivalence margin between groups with an alpha of 5% and a power of 80%. Equivalence analysis was performed with a two one-sided test (TOST) in which a p value of

Background In patients with adverse local tissue reaction (ALTR) secondary to a failed metal-on-metal (MoM) bearing or corrosion at the head-neck junction in a metal-on-polyethylene bearing, ruling in or out periprosthetic joint infection (PJI) can be challenging. Alpha-defensin has emerged as an accurate test for PJI. The purpose of this multicenter, retrospective study was to evaluate the accuracy of the alpha-defensin synovial fluid test in detecting PJI in patients with ALTR. Methods We reviewed medical records of 26 patients from 3 centers with ALTR that had an alpha-defensin test performed. Patients were assessed for PJI using the Musculoskeletal Infection Society criteria. Thirteen of these subjects had MoM total hip arthroplasty, 9 had ALTR secondary to head-neck corrosion, and 4 had MoM hip resurfacing. Results Only 1 of the 26 patients met Musculoskeletal Infection Society criteria for infection. However, 9 hips were alpha-defensin positive, including 1 true positive and 8 that were falsely positive (31%). All 8 of the false positives were also Synovasure positive, although 5 of 8 had an accompanying warning stating the results may be falsely positive due to a low synovial C-reactive protein value. Conclusion Similar to synovial fluid white blood cell count, alpha-defensin testing is prone to false-positive results in the setting of ALTR. Therefore, we recommend an aggressive approach to ruling out PJI including routine aspiration of all hips with ALTR before revision surgery to integrate the synovial fluid blood cell count, differential, cultures and adjunctive tests like alpha-defensin to allow for accurate diagnosis preoperatively.

Background Time trade-off, standard gamble, and willingness to pay assess the number of years, risk of death, and income a patient would give up for perfect health. These questions were used to evaluate the impact knee arthritis, hip arthritis, or failed total knee (TKA) or hip arthroplasty (THA) has on patients’ health-related quality of life prior to surgery. Methods Three hundred sixty patients including 176 undergoing primary TKA, 127 undergoing primary THA, 31 undergoing revision TKA, and 26 undergoing revision THA were assessed. Time trade-off and standard gamble were converted to utility scores with 1.0 suggesting perfect health and 0 suggesting preference for death rather than living in current state. Willingness to pay is the percentage of yearly income that a patient would pay for perfect health. Results The mean time trade-off, standard gamble, and willingness to pay scores were 0.74, 0.83, and 0.32 without significant difference between procedures with the numbers available for study (P = .16, .31, and 0.41, respectively). Increasing body mass index was correlated with decreasing time trade-off scores (P = .014). Conclusion Patients scheduled for primary or revision THA and TKA would accept an average 17% risk of death, lose 2.6 years of an additional 10-year life expectancy, and pay 32% of their income for perfect health. The time trade-off (0.74) was similar to patients with history of acute myocardial infarction (0.74) or minor stroke (0.72) and worse than those with chronic hepatitis C (0.83) or human immunodeficiency virus/acquired immunodeficiency syndrome infection (0.86). These data highlight the high value that patients place on adult reconstructive procedures.

Background Treatment of periprosthetic joint infections commonly involves insertion of an antibiotic-loaded cement spacer (ACS). The risk for acute kidney injury (AKI) related to use of antibiotic spacers has not been well defined. We aimed to identify the incidence of and risk factors for AKI after placement of an ACS. Methods We performed a prospective cohort study of patients with an infected primary total hip or knee arthroplasty treated with ACSs with vancomycin, gentamicin, and tobramycin. Serum creatinine and glomerular filtration rate data were collected at baseline and weekly intervals for 8 weeks. Patients were classified into Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) stages to determine incidence of AKI. Risk factors for kidney injury were identified via regression analysis. Results A total of 37 patients (20 total knee arthroplasty and 17 total hip arthroplasty) were included. During the 8 weeks after ACS placement, 10 patients (27%) fit RIFLE criteria for kidney injury and 2 patients (5%) fit RIFLE criteria for kidney failure. No baseline patient characteristics were associated with development of AKI. Conclusion Patients should be monitored closely for development of AKI after placement of ACSs for the treatment of periprosthetic joint infection. Further research into minimizing risk for AKI is warranted.

Background One proposed strategy to increase the success of irrigation and debridement with implant retention for the treatment of acute periprosthetic joint infection (PJI) is the use of dissolvable antibiotic-impregnated calcium sulfate beads to provide a local depot of antibiotics. The purpose of this study was to evaluate the outcome of such an approach. Methods Thirty-two patients with acute hematogenous (18 patients; 1 bilateral) or acute postoperative (14 patients) PJIs who underwent irrigation and debridement with implant retention and addition of antibiotic-impregnated calcium sulfate beads were retrospectively reviewed. PJI followed 27 total knee arthroplasties and 6 total hip arthroplasties. The most common infecting organisms were methicillin-sensitive Staphylococcus aureus (13 of 33) and Streptococcus (9 of 33). The primary outcome parameter was recurrence of infection according to the Musculoskeletal Infection Society criteria. Patients were followed up for a minimum of 3 months or until failure. Results At a mean of 12.7 months (range, 3-30 months), 16 of the 33 patients failed (48%). Acute hematogenous and acute postoperative PJI had similar failure rates at 47% and 50%, respectively ( P = .88). Seven failures required a 2-stage exchange, while 8 patients were treated with chronic antibiotic suppression, being unwilling or unable to undergo further surgical intervention. Conclusion The addition of antibiotic-impregnated calcium sulfate beads does not appear to improve outcomes of irrigation and debridement with implant retention in the setting of acute hematogenous or acute postoperative PJI. Given the short follow-up in this report, this represents a best-case scenario and the overall failure rate may be higher with further follow-up.

Many patients develop recurrent periprosthetic joint infection after two-stage exchange arthroplasty of the hip or knee. One potential but insufficiently tested strategy to decrease the risk of persistent or recurrent infection is to administer additional antibiotics after the second-stage reimplantation.(1) Does a 3-month course of oral antibiotics decrease the risk of failure secondary to infection after a two-stage exchange? (2) Are there any complications related to the administration of oral antibiotics after a two-stage exchange? (3) In those patients who develop a reinfection, is the infecting organism different from the initial infection?Patients at seven centers randomized to receive 3 months of oral antibiotics or no further antibiotic treatment after operative cultures after the second-stage reimplantation were negative. Adult patients undergoing two-stage hip or knee revision arthroplasty for a periprosthetic infection who met Musculoskeletal Infection Society (MSIS) criteria for infection at the first stage were included. Oral antibiotic therapy was tailored to the original infecting organism(s) in consultation with an infectious disease specialist. MSIS criteria as used by the treating surgeon defined failure. Surveillance of patients for complications, including reinfection, occurred at 3 weeks, 6 weeks, 3 months, 12 months, and 24 months. If an organism demonstrated the same antibiotic sensitivities as the original organism, it was considered the same organism; no DNA subtyping was performed. Analysis was performed as intent to treat with all randomized patients included in the groups to which they were randomized. A log-rank survival curve was used to analyze the primary outcome of reinfection. At planned interim analysis (enrollment is ongoing), 59 patients were successfully randomized to the antibiotic group and 48 patients to the control group. Fifty-seven patients had an infection after TKA and 50 after a THA. There was no minimum followup for inclusion in this analysis. The mean followup was 14 months in the antibiotic group and 10 months in the control group.Patients treated with oral antibiotics failed secondary to infection less frequently than those not treated with antibiotics (5% [three of 59] versus 19% [nine of 48]; hazard ratio, 4.37; 95% confidence interval, 1.297-19.748; p = 0.016). Three patients had an adverse reaction to the oral antibiotics severe enough to cause them to stop taking the antibiotics early, and four patients who were randomized to that group did not take the antibiotics as directed. With the numbers available, there were no differences between the study groups in terms of the likelihood that an infection after treatment would be with a new organism (eight of nine in the control group versus one of three in the treatment group, p = 0.087).This multicenter randomized trial suggests that at short-term followup, the addition of 3 months of oral antibiotics appeared to improve infection-free survival. As a planned interim analysis, however, these results may change as the study reaches closure and the safety profile may yet prove risky. Further followup of this cohort of patients will be necessary to determine whether these preliminary results are durable over time.Level I, therapeutic study.