Incidence, Microbiological Studies, and Factors Associated With Prosthetic Joint Infection After Total Knee Arthroplasty.

Importance: Despite the frequency of total knee arthroplasty (TKA) and clinical implications of prosthetic joint infections (PJIs), knowledge gaps remain concerning the incidence, microbiological study results, and factors associated with these infections. Objectives: To identify the incidence rates, organisms isolated from microbiological studies, and patient and surgical factors of PJI occurring early, delayed, and late after primary TKA. Design, Setting, and Participants: This cohort study obtained data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse on patients who underwent elective primary TKA in the VA system between October 1, 1999, and September 30, 2019, and had at least 1 year of care in the VA prior to TKA. Patients who met these criteria were included in the overall cohort, and patients with linked Veterans Affairs Surgical Quality Improvement Program (VASQIP) data composed the VASQIP cohort. Data were analyzed between December 9, 2021, and September 18, 2023. Exposures: Primary TKA as well as demographic, clinical, and perioperative factors. Main Outcomes and Measures: Incident hospitalization with early, delayed, or late PJI. Incidence rate (events per 10 000 person-months) was measured in 3 postoperative periods: early (≤3 months), delayed (between >3 and ≤12 months), and late (>12 months). Unadjusted Poisson regression was used to estimate incidence rate ratios (IRRs) with 95% CIs of early and delayed PJI compared with late PJI. The frequency of organisms isolated from synovial or operative tissue culture results of PJIs during each postoperative period was identified. A piecewise exponential parametric survival model was used to estimate IRRs with 95% CIs associated with demographic and clinical factors in each postoperative period. Results: The 79 367 patients (median (IQR) age of 65 (60-71) years) in the overall cohort who underwent primary TKA included 75 274 males (94.8%). A total of 1599 PJIs (2.0%) were identified. The incidence rate of PJI was higher in the early (26.8 [95% CI, 24.8-29.0] events per 10 000 person-months; IRR, 20.7 [95% CI, 18.5-23.1]) and delayed periods (5.4 [95% CI, 4.9-6.0] events per 10 000 person-months; IRR, 4.2 [95% CI, 3.7-4.8]) vs the late postoperative period (1.3 events per 10 000 person-months). Staphylococcus aureus was the most common organism isolated overall (489 [33.2%]); however, gram-negative infections were isolated in 15.4% (86) of early PJIs. In multivariable analyses, hepatitis C virus infection, peripheral artery disease, and autoimmune inflammatory arthritis were associated with PJI across all postoperative periods. Diabetes, chronic kidney disease, and obesity (body mass index of ≥30) were not associated factors. Other period-specific factors were identified. Conclusions and Relevance: This cohort study found that incidence rates of PJIs were higher in the early and delayed vs late post-TKA period; there were differences in microbiological cultures and factors associated with each postoperative period. These findings have implications for postoperative antibiotic use, stratification of PJI risk according to postoperative time, and PJI risk factor modification.

Development and validation of case-finding algorithms to identify prosthetic joint infections after total knee arthroplasty in Veterans Health Administration data.

PURPOSE: To determine the positive predictive values (PPVs) of ICD-9, ICD-10, and current procedural terminology (CPT)-based diagnostic coding algorithms to identify prosthetic joint infection (PJI) following knee arthroplasty (TKA) within the United States Veterans Health Administration. METHODS: We identified patients with: (1) hospital discharge ICD-9 or ICD-10 diagnosis of PJI, (2) ICD-9, ICD-10, or CPT procedure code for TKA prior to PJI diagnosis, (3) CPT code for knee X-ray within ±90 days of the PJI diagnosis, and (4) at least 1 CPT code for arthrocentesis, arthrotomy, blood culture, or microbiologic procedure within ±90 days of the PJI diagnosis date. Separate samples of patients identified with the ICD-9 and ICD-10-based PJI diagnoses were obtained, stratified by TKA procedure volume at each medical center. Medical records of sampled patients were reviewed by infectious disease clinicians to adjudicate PJI events. The PPV (95% confidence interval [CI]) for the ICD-9 and ICD-10 PJI algorithms were calculated. RESULTS: Among a sample of 80 patients meeting the ICD-9 PJI algorithm, 60 (PPV 75.0%, [CI 64.1%-84.0%]) had confirmed PJI. Among 80 patients who met the ICD-10 PJI algorithm, 68 (PPV 85.0%, [CI 75.3%-92.0%]) had a confirmed diagnosis. CONCLUSIONS: An algorithm consisting of an ICD-9 or ICD-10 PJI diagnosis following a TKA code combined with CPT codes for a knee X-ray and either a relevant surgical procedure or microbiologic culture yielded a PPV of 75.0% (ICD-9) and 85.0% (ICD-10), for confirmed PJI events and could be considered for use in future pharmacoepidemiologic studies.

Diagnosis of Periprosthetic Joint Infection: The Potential of Next-Generation Sequencing.

BACKGROUND: Next-generation sequencing is a well-established technique for sequencing of DNA and has recently gained attention in many fields of medicine. Our aim was to evaluate the accuracy of next-generation sequencing in identifying the causative organism(s) in patients with periprosthetic joint infection. METHODS: In this prospective study, samples were collected from 65 revision arthroplasties (39 knees and 26 hips) and 17 primary arthroplasties (9 hips and 8 knees). Synovial fluid, deep tissue, and swabs were obtained at the time of the surgical procedure and were shipped to the laboratory for next-generation sequencing. Deep-tissue specimens were also sent to the institutional laboratory for culture. Sensitivity and specificity were calculated for next-generation sequencing, using the Musculoskeletal Infection Society (MSIS) definition of periprosthetic joint infection as the standard. RESULTS: In 28 revisions, the cases were considered to be infected; cultures were positive in 17 cases (60.7% [95% confidence interval (CI), 40.6% to 78.5%]), and next-generation sequencing was positive in 25 cases (89.3% [95% CI, 71.8% to 97.7%]), with concordance between next-generation sequencing and culture in 15 cases. Among the 11 cases of culture-negative periprosthetic joint infection, next-generation sequencing was able to identify an organism in 9 cases (81.8% [95% CI, 48.2% to 97.7%]). Next-generation sequencing identified microbes in 9 (25.0% [95% CI, 12.1% to 42.2%]) of 36 aseptic revisions with negative cultures and in 6 (35.3% [95% CI, 14.2% to 61.7%]) of 17 primary total joint arthroplasties. Next-generation sequencing detected several organisms in most positive samples. However, in the majority of patients who were infected, 1 or 2 organisms were dominant. CONCLUSIONS: Next-generation sequencing may be a useful adjunct in identification of the causative organism(s) in culture-negative periprosthetic joint infection. Our findings suggest that some cases of monomicrobial periprosthetic joint infection may have additional organisms that escape detection when culture is used. Further study is required to determine the clinical implications of isolated organisms in samples from patients who are not thought to be infected. LEVEL OF EVIDENCE: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Tick-borne illness after transplantation: Case and review.

Tick-borne infections in solid organ transplant recipients are an infrequent and difficult diagnostic challenge owing to multiple routes of acquisition and unusual presentations. A 67-year-old male recipient of a combined liver and kidney transplant presented with recurrent fevers following surgery. Standard microbiologic workup was non-diagnostic. Shortness of breath, confusion, lethargy, and hypotension developed along with progressive anemia, requiring multiple blood transfusions. Workup suggested hemolysis and review of the peripheral smear was diagnostic for Babesia microti infection. Tick transmission, transmission via blood products, and/or the transplanted organ were all considered. More extensive questioning revealed a history of intermittent fevers for several months before transplantation. Testing of pre-transplant blood was positive for B. microti antibodies, suggesting infection prior to transplantation. The delayed diagnosis of babesiosis in this patient highlights the need for a detailed exposure history prior to transplantation, as well as considering the potential for atypical presentations of tick-borne infections in immune suppressed solid organ recipients. Furthermore, this case illustrates the importance of early Infectious Disease consultation to meet the challenges exhibited by febrile transplant patients. Infectious Diseases physicians are trained to consider, diagnose, and treat tick-borne infections, contributing to improved clinical outcome.

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

BACKGROUND: 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. 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? METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 OF EVIDENCE: Level I, therapeutic study.