Kamil T. Okroj

The Mark Coventry, MD, Award: Oral Antibiotics Reduce Reinfection After Two-Stage Exchange: A Multicenter, Randomized Controlled Trial

BackgroundMany 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.Questions/purposes(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?MethodsPatients 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.ResultsPatients 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).ConclusionsThis 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 of EvidenceLevel I, therapeutic study.

Periprosthetic Joint Infection After Hip and Knee Arthroplasty: A Review for Emergency Care Providers

Periprosthetic joint infection is among the most common modes of failure of a total hip or knee arthroplasty and can be a common concern when patients present to the emergency department for care. The initial evaluation for periprosthetic joint infection includes a history and physical examination, followed by radiographs (to rule out other causes of pain or failure) and then serum erythrocyte sedimentation rate and C-reactive protein testing. If the erythrocyte sedimentation rate and C-reactive protein level are elevated or if the clinical suspicion for infection is high, the joint should be aspirated and the fluid sent for culture, as well as for a synovial WBC count and differential, with optimal threshold values of 3,000 WBC/μL and 80% polymorphonuclear cells, respectively. Recent work has shown that optimal cutoff values for patients presenting in the early postoperative period (within the first 6 weeks postoperatively) are different, with a C-reactive protein level greater than or near 100 mg/L (normal <10 mg/L), indicating the need for aspiration, with synovial fluid WBC thresholds of 10,000 WBC/μL and 90% polymorphonuclear cells. Antibiotics should not be administered before joint aspiration unless the patient has systemic signs of sepsis because even a single dose may cloud the interpretation of subsequent tests, including cultures taken from the joint. Furthermore, superficial cultures taken from wound drainage are discouraged because they can similarly cloud diagnosis and treatment. The rising prevalence of total joint arthroplasty makes proficiency in the assessment and early management of periprosthetic joint infection important for the emergency physician to optimize clinical outcomes.

Nephrotoxicity After the Treatment of Periprosthetic Joint Infection With Antibiotic-Loaded Cement Spacers

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.

The Alpha-Defensin Test for Diagnosing Periprosthetic Joint Infection in the Setting of an Adverse Local Tissue Reaction Secondary to a Failed Metal-on-Metal Bearing or Corrosion at the Head-Neck Junction.

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.