Irrigation and Debridement With Chronic Antibiotic Suppression for the Management of Acutely Infected Aseptic Revision Total Joint Arthroplasties.

BACKGROUND: Most data on irrigation and debridement with component retention (IDCR) as a treatment for acute periprosthetic joint infections (PJIs) focuses on primary total joint arthroplasties (TJAs). However, the incidence of PJI is greater after revisions. We investigated the outcomes of IDCR with suppressive antibiotic therapy (SAT) following aseptic revision TJAs. METHODS: Through our total joint registry, we identified 45 aseptic revision TJAs (33 hips, 12 knees) performed from 2000 to 2017 that were treated with IDCR for acute PJI. Acute hematogenous PJI was present in 56%. Sixty-four percent of PJIs involved Staphylococcus. All patients were treated with 4 to 6 weeks of intravenous antibiotics with the intention to treat with SAT (89% received SAT). The mean age was 71 years (range, 41 to 90), with 49% being women and a mean body mass index of 30 (range, 16 to 60). The mean follow-up was 7 years (range, 2 to 15). RESULTS: The 5-year survivorships free from re-revision for infection and reoperation for infection were 80% and 70%, respectively. Of the 13 reoperations for infection, 46% involved the same species as the initial PJI. The 5-year survivorships free from any revision and any reoperation were 72% and 65%, respectively. The 5-year survivorship free from death was 65%. CONCLUSION: At 5 years following IDCR, 80% of implants were free from re-revision for infection. As the penalty for implant removal is often high in revision TJAs, IDCR with SAT is a viable option for acute infection after revision TJAs in select patients. LEVEL OF EVIDENCE: IV.

Outcomes in patients with clinically suspected pedal osteomyelitis based on bone marrow signal pattern on MRI.

Objective: confluent T1 hypointense marrow signal is widely accepted to represent osteomyelitis on MRI. Some authors have suggested that non-confluent bone marrow signal abnormality should be considered early osteomyelitis. The purpose of this study was to address this issue by comparing the rate of osteomyelitis and amputation based on T1 marrow signal characteristics. Materials and methods: a total of 112 patients who underwent MRI of the foot for the evaluation of possible osteomyelitis were included. Patients were assigned to confluent T1 hypointense, reticulated T1 hypointense, and normal bone marrow signal groups. Results: patients with confluent T1 hypointense signal on MRI had significantly higher rates of osteomyelitis and amputation at 2 and 14 months post-MRI than the reticulated T1 hypointense group ( p < 0.001 ). Six patients had normal T1 signal, 16.7 % of whom had osteomyelitis and underwent amputation by 2 months post-MRI. Of 61 patients with reticulated T1 hypointense signal, 19.7 % had a diagnosis of osteomyelitis at 2 months post-MRI and 30.8 % had a diagnosis of osteomyelitis at 14 months post-MRI; moreover, 14.8 % and 31.5 % underwent amputation by 2 and 14 months post-MRI, respectively. Of 45 patients with confluent T1 hypointense signal, 73.3 % of patients had osteomyelitis at 2 months post-MRI and 82.5 % had osteomyelitis at 14 months post-MRI. In this group, 66.7 % underwent amputation by 2 months post-MRI and 77.8 % underwent amputation by 14 months post-MRI. Conclusions: over half of the patients with suspected pedal osteomyelitis who had reticulated or normal T1 bone marrow signal on MRI healed with conservative measures. Therefore, we recommend terminology such as "osteitis", "reactive osteitis", or "nonspecific reactive change" to describe bone marrow edema-like signal and reticulated hazy T1 hypointense signal without associated confluent T1 hypointensity. Moreover, we recommend that the MRI diagnosis of osteomyelitis is reserved for confluent T1 hypointense bone signal in the area of concern.

Short Course of Oral Antibiotic Treatment After Two-Stage Exchange Arthroplasty Appears to Decrease Early Reinfection.

BACKGROUND: Recent evidence has suggested a benefit to extended postoperative prophylactic oral antibiotics after two-stage exchange arthroplasty for treatment of periprosthetic joint infections. We sought to determine reinfection rates with and without a short course of oral antibiotics after two-stage exchange procedures. METHODS: A retrospective review identified patients undergoing two-stage exchange arthroplasty for periprosthetic joint infection of the hip or knee. Patients were excluded if they failed a prior two-stage exchange, had positive cultures at reimplantation, prolonged intravenous antibiotics postoperatively, and/or life-long suppression. This resulted in 444 reimplantations (210 hips and 234 knees). Patients were divided into three cohorts based on the duration of oral antibiotics after reimplantation: no antibiotics (102), ≤2 weeks (266), or >2 weeks (76). The primary endpoint was reinfection within 1 year of reimplantation. RESULTS: Within 1 year of reimplantation, there were 34 reinfections. In the no-antibiotic, ≤ 2-week, and >2-week cohorts the reinfection rates were 14.1, 7.0, and 6.4%, respectively. Multivariate Cox regression showed a reduced reinfection rate in the ≤2-week cohort relative to no antibiotics (hazard ratio [HR]: 0.38, P = .01). While the smaller cohort with >2 weeks of antibiotics did not significantly reduce the reinfection rate (HR: 0.41, P = .12), when combined with the ≤2-week cohort, use of oral antibiotics had an overall reduction of the reinfection rate (HR: 0.39, P = .01). CONCLUSIONS: These data support the hypothesis that a short course of oral antibiotics after reimplantation decreases the 1-year reinfection rate. Future randomized studies should seek to examine the efficacy of different durations of oral antibiotics to reduce reinfection. LEVEL OF EVIDENCE: Prognostic Level IV.

Extended Oral Antibiotic Prophylaxis After Aseptic Revision Total Hip Arthroplasty: Does It Decrease Infection Risk?

BACKGROUND: Extended oral antibiotic prophylaxis (EOA) has been shown to reduce infection after high-risk primary total hip arthroplasties (THAs) and reimplantations. However, data are limited regarding EOA after aseptic revision THAs. This study evaluated the impact of EOA on infection-related outcomes after aseptic revision THAs. METHODS: We retrospectively identified 1,107 aseptic revision THAs performed between 2014 and 2019. Patients who received EOA >24 hours perioperatively (n = 370) were compared to those who did not (n = 737) using an inverse probability of treatment weighting model. Their mean age was 65 years (range, 19-98 years), mean body mass index was 30 kg/m2 (range, 16-72), and 54% were women. Outcomes included cumulative probabilities of any infection, periprosthetic joint infection (PJI), and re-revision or reoperation for infection. Mean follow-up was 4 years (range, 2-8 years). RESULTS: The cumulative probability of any infection after aseptic revision THA was 2.3% at 90 days, 2.7% at 1 year, and 3.5% at 5 years. The cumulative probability of PJI was 1.7% at 90 days, 2.1% at 1 year, and 2.8% at 5 years. There was a trend toward an increased risk of any infection (hazards ratio [HR] = 2.6; P = .058), PJI (HR = 2.6; P = .085), and re-revision (HR = 6.5; P = .077) or reoperation (HR = 2.3; P = .095) for infection in patients who did not have EOA at the final clinical follow-up. CONCLUSIONS: EOA after aseptic revision THA was not associated with a statistically significant decreased risk of any infection, PJI, or re-revision or reoperation for infection at all time points. LEVEL OF EVIDENCE: Level III.

Extended Oral Antibiotic Prophylaxis After Aseptic Revision TKA: Does It Decrease Infection Risk?

BACKGROUND: Extended oral antibiotic prophylaxis (EOA) has been shown to potentially reduce infection rates after high-risk primary total knee arthroplasties (TKAs) and reimplantations. However, data is limited regarding EOA after aseptic revision TKAs. This study evaluated the impact of EOA on infection-related outcomes after aseptic revision TKAs. METHODS: 904 aseptic revision TKAs from 2014-2019 were retrospectively identified. Patients who received EOA >24 hours perioperatively (n = 267) were compared to those who did not (n = 637) using an inverse probability of treatment weighting model. Mean age was 66 years, mean BMI was 33 kg/m2, and 54% were female. Outcomes included cumulative probabilities of any infection, periprosthetic joint infection (PJI), superficial infection, and re-revision or reoperation for infection. RESULTS: The cumulative probability of any infection after aseptic revision TKA was 1.9% at 90 days, 3.5% at 1 year, and 8.1% at 5 years. Patients without EOA had a higher risk of any infection at 90 days (HR = 7.1; P = .01), but not other time points. The cumulative probability of PJI after aseptic revision TKA was 0.8% at 90 days, 2.3% at 1 year, and 6.5% at 5 years. Patients without EOA did not have an increased risk of PJI. There were no differences in re-revision or reoperation for infection at any time point between groups. CONCLUSION: Extended oral antibiotics after aseptic revision TKA were associated with a 7-fold decreased risk of any infection at 90 days. The results suggest a potential role for EOA after aseptic revision TKA and warrant additional prospective studies. LEVEL OF EVIDENCE: Level III.

Recent Antibiotic Treatment Impacts Serum and Synovial Laboratory Values in Early Periprosthetic Joint Infection Workup.

BACKGROUND: Accurately detecting early postoperative periprosthetic joint infection (PJI) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) remains challenging. The purpose of our study was to determine the impact of antibiotics given prior to laboratory evaluation on the reliability of serologic and synovial fluid tests to identify PJI in the early postoperative period. METHODS: We identified 49,861 primary total hip arthroplasties and total knee arthroplasties performed between 2000 and 2019. Among these patients, 21 hips and 28 knees that underwent arthrocentesis within 12 weeks of their arthroplasty were identified as infected. Patients who had received antibiotics within 2 weeks prior to laboratory evaluation were compared to those who had not. Median values of C-reactive protein, erythrocyte sedimentation rate, synovial white blood cell (WBC) count, synovial neutrophil percentage, and synovial absolute neutrophil count were compared between groups. The false negative rate for detecting PJI using laboratory values was compared using published cutoffs for PJI in the early postoperative period. RESULTS: Median values of C-reactive protein (105 vs 22 mg/L; P = .006), synovial WBC count (57,591 vs 4,473 cells/µL; P = .003), synovial neutrophil percentage (94% vs 76%; P = .004), and synovial absolute neutrophil count (50,748 vs 2,804 cells/µL; P < .001) were significantly lower in patients who received antibiotics compared to those who did not. False negative rates for detecting PJI were significantly higher for synovial WBC and synovial neutrophil percentage in patients treated with antibiotics compared to untreated patients. CONCLUSION: False negative rates for detecting early PJI when using published cutoffs were markedly higher in antibiotic-treated patients compared to untreated patients for synovial WBC count and synovial neutrophil percentage. LEVEL OF EVIDENCE: Level IV retrospective review.

Outcomes of primary total hip arthroplasty following septic arthritis of the hip : a case-control study.

AIMS: Septic arthritis of the hip often leads to irreversible osteoarthritis (OA) and the requirement for total hip arthroplasty (THA). The aim of this study was to report the mid-term risk of any infection, periprosthetic joint infection (PJI), aseptic revision, and reoperation in patients with a past history of septic arthritis who underwent THA, compared with a control group of patients who underwent THA for OA. METHODS: We retrospectively identified 256 THAs in 244 patients following septic arthritis of the native hip, which were undertaken between 1969 and 2016 at a single institution. Each case was matched 1:1, based on age, sex, BMI, and year of surgery, to a primary THA performed for OA. The mean age and BMI were 58 years (35 to 84) and 31 kg/m2 (18 to 48), respectively, and 100 (39%) were female. The mean follow-up was 11 years (2 to 39). RESULTS: The ten-year survival free of any infection was 91% and 99% in the septic arthritis and OA groups, respectively (hazard ratio (HR) = 13; p < 0.001). The survival free of PJI at ten years was 93% and 99% in the septic arthritis and OA groups, respectively (HR = 10; p = 0.002). There was a significantly higher rate of any infection at ten years when THA was undertaken within five years of the diagnosis of septic arthritis compared with those in whom THA was undertaken > five years after this diagnosis was made (14% vs 5%, respectively; HR = 3.1; p = 0.009), but there was no significant difference in ten-year survival free of aseptic revision (HR = 1.14; p = 0.485). The mean Harris Hip Scores at two and five years postoperatively were significantly lower in the septic arthritis group compared with the OA group (p = 0.001 for both). CONCLUSION: There was a ten-fold increased risk of PJI in patients with a history of septic arthritis who underwent THA compared with those who underwent THA for OA with a ten-year cumulative incidence of 7%. The risk of any infection had a strong downward trend as the time interval between the diagnosis of septic arthritis and THA increased, highlighted by a 3.1-fold higher risk when THAs were performed within five years of the diagnosis being made. Cite this article: Bone Joint J 2022;104-B(2):227-234.

Laboratory Value Effectiveness in Predicting Early Postoperative Periprosthetic Joint Infection After Total Hip Arthroplasty.

BACKGROUND: Diagnosing early periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) remains challenging. We sought to validate optimal laboratory value cutoffs for detecting early PJIs in a series of primary THAs from one institution. METHODS: We retrospectively identified 22,795 primary THAs performed between 2000 and 2019. Within 12 weeks, 43 hips (43 patients) underwent arthrocentesis. Patients were divided into 2 groups: evaluation ≤6 weeks or 6-12 weeks following THA. The 2011 Musculoskeletal Infection Society major criteria for PJI diagnosed PJI in 15 patients. Mann-Whitney U-tests were used to compare median laboratory values and receiver operating characteristic curve analysis was used to evaluate optimal cutoff values. RESULTS: Both within 6 weeks and between 6 and 12 weeks postoperatively, median C-reactive protein (CRP), erythrocyte sedimentation rate, synovial white blood cell (WBC) count, neutrophil percentage, and absolute neutrophil count (ANC) values were significantly higher in infected THAs. Optimal cutoffs within 6 weeks were: CRP ≥100 mg/L, synovial WBCs ≥4390 cells/µL, neutrophil percentage ≥74%, and ANC ≥3249 cells/µL. Between 6 and 12 weeks, optimal cutoffs were: CRP ≥33 mg/L, synovial WBCs ≥26,995 cells/µL, neutrophil percentage ≥93%, and ANC ≥25,645 cells/µL. CONCLUSION: Early PJI following THA should be suspected within 6 weeks with CRP ≥100 mg/L or synovial WBCs ≥4390 cells/µL. Between 6 and 12 weeks postoperatively, cutoffs of CRP ≥33 mg/L, synovial fluid WBC ≥26,995 cells/µL, and neutrophil percentage ≥93% diagnosed PJI with high accuracy. LEVEL OF EVIDENCE: Level IV Diagnostic.

Outcomes of Primary Total Knee Arthroplasty Following Septic Arthritis of the Native Knee: A Case-Control Study.

BACKGROUND: Septic arthritis of the native knee often results in irreversible joint damage leading to the need for total knee arthroplasty (TKA). The purpose of the present study was to examine the intermediate-term risk of periprosthetic joint infection (PJI), aseptic revision, and reoperation following primary TKA in patients with a history of septic arthritis of the native knee as compared with primary TKA performed for the treatment of osteoarthritis. METHODS: We retrospectively identified 215 primary TKAs performed from 1971 to 2016 at a single institution in patients with a history of septic arthritis of the native knee. Each case was matched 1:1 based on age, sex, body mass index (BMI), and surgical year to a TKA for osteoarthritis. The mean age and BMI were 63 years and 30 kg/m2, respectively. The mean duration of follow-up was 9 years. RESULTS: Survivorships free of PJI at 10 years were 90% and 99% for the septic arthritis and osteoarthritis groups, respectively (hazard ratio [HR] = 6.1; p < 0.01). Ten-year survivorships free of any aseptic revisions were 83% and 93% (HR = 2.5; p < 0.01), and survivorships free of any reoperation were 61% and 84% (HR = 2.9; p < 0.01) for the septic arthritis and osteoarthritis groups, respectively. In addition, as time from the diagnosis of native knee septic arthritis to TKA increased, the relative risk of subsequent infection decreased. Preoperative and 2-year postoperative Knee Society scores were similar between the groups (p = 0.16 and p = 0.19, respectively). CONCLUSIONS: There was a 6.1-fold increased risk of PJI in patients undergoing TKA with a history of native knee septic arthritis when compared with controls undergoing TKA for the treatment of osteoarthritis, with a cumulative incidence of 9% at 10 years. Subgroup analysis of the septic arthritis cohort revealed a higher risk of any infection in patients who underwent TKA within the first 5 to 7 years after the diagnosis of septic arthritis as compared with those with a greater duration. Moreover, the 10-year rates of survival free of aseptic revision, any revision, and any reoperation were significantly worse in the native knee septic arthritis cohort. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

In Vitro Activity of Rifampin, Rifabutin, and Rifapentine against Enterococci and Streptococci from Periprosthetic Joint Infection.

After staphylococci, streptococci and enterococci are the most frequent causes of periprosthetic joint infection (PJI). MICs and minimum biofilm bactericidal concentrations of rifampin, rifabutin, and rifapentine were determined for 67 enterococcal and 59 streptococcal PJI isolates. Eighty-eight isolates had rifampin MICs of ≤1 µg/ml, among which rifabutin and rifapentine MICs were ≤ 8 and ≤4 µg/ml, respectively. There was low rifamycin in vitro antibiofilm activity except for a subset of Streptococcus mitis group isolates. IMPORTANCE Rifampin is an antibiotic with antistaphylococcal biofilm activity used in the management of staphylococcal periprosthetic joint infection with irrigation and debridement with component retention; some patients are unable to receive rifampin due to drug interactions or intolerance. We recently showed rifabutin and rifapentine to have in vitro activity against planktonic and biofilm states of rifampin-susceptible periprosthetic joint infection-associated staphylococci. After staphylococci, streptococci and enterococci combined are the most common causes of periprosthetic joint infection. Here, we investigated the in vitro antibiofilm activity of rifampin, rifabutin, and rifapentine against 126 Streptococcus and Enterococcus periprosthetic joint infection isolates. In contrast to our prior findings with staphylococcal biofilms, there was low antibiofilm activity of rifampin, rifabutin, and rifapentine against PJI-associated streptococci and enterococci, apart from some Streptococcus mitis group isolates.

Safety and tolerability of liquid amikacin in antibiotic-loaded bone cement - a case series.

High-dose liquid antibiotics are uncommon in bone cement. We present a case series of patients in which up to 16 mL of liquid amikacin (250 mg mL - 1 ) was successfully incorporated into bone cement to treat periprosthetic joint infections. We did not observe adverse drug reactions definitively attributed to its use.

Synovial fluid α defensin has comparable accuracy to synovial fluid white blood cell count and polymorphonuclear percentage for periprosthetic joint infection diagnosis.

AIMS: The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. METHODS: Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar's test and area under the receiver operating characteristic curve (AUC) analysis. RESULTS: Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. CONCLUSION: The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119-1126.

The effectiveness of laboratory tests to predict early postoperative periprosthetic infection after total knee arthroplasty.

AIMS: It remains difficult to diagnose early postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). We aimed to validate the optimal cutoff values of ESR, CRP, and synovial fluid analysis for detecting early postoperative PJI in a large series of primary TKAs. METHODS: We retrospectively identified 27,066 primary TKAs performed between 2000 and 2019. Within 12 weeks, 169 patients (170 TKAs) had an aspiration. The patients were divided into two groups: those evaluated ≤ six weeks, or between six and 12 weeks postoperatively. The 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI diagnosis in 22 TKAs. The mean follow-up was five years (two months to 17 years). The results were compared using medians and Mann-Whitney U tests and thresholds were analyzed using receiver operator characteristic curves. RESULTS: Within six weeks, the median CRP (101 mg/l vs 35 mg/l; p = 0.011), synovial WBCs (58,295 cells/µl vs 2,121 cells/µl; p ≤ 0.001), percentage of synovial neutrophils (91% vs 71% (p < 0.001), and absolute synovial neutrophil count (ANC) (50,748 cells/µl vs 1,386 cells/µl (p < 0.001) were significantly higher in infected TKAs. Between six and 12 weeks, the median CRP (85 mg/l vs 5 mg/l (p < 0.001)), ESR (33 mm/hr vs 14 mm/hr (p = 0.015)), synovial WBCs (62,247 cells/µl vs 620 cells/µl (p < 0.001)), percentage of synovial neutrophils (93% vs 54% (p < 0.001)), and ANC (55,911 cells/µl vs 326 cells/µl (p < 0.001)) were also significantly higher in infected TKAs. Optimal thresholds at ≤ six weeks were: CRP ≥ 82 mg/l (sensitivity 70%, specificity 77%), synovial WBCs ≥ 8,676 cells/µl (83%, 90%), percentage of synovial neutrophils ≥ 88% (67%, 78%), and ANC ≥ 8,346 cells/µl (83%, 91%). Between six and 12 weeks, thresholds were: CRP ≥ 34 mg/l (90%, 93%), synovial WBCs ≥ 1,983 cells/µl (80%, 85%), percentage of synovial neutrophils ≥ 76% (80%, 81%), and ANC ≥ 1,684 cells/µl (80%, 87%). CONCLUSION: Early PJI after TKA should be suspected within six weeks if the CRP is ≥ 82 mg/l, synovial WBCs are ≥ 8,676 cells/µl, the percentage of synovial neutrophils is ≥ 88%, and/or the ANC is ≥ 8,346 cells/µl. Between six and 12 weeks, thresholds include a CRP of ≥ 34 mg/l, synovial WBC of ≥ 1,983 cells/µl, a percentage of synovial neutrophils of ≥ 76%, and/or an ANC of ≥ 1,684 cells/µl. Cite this article: Bone Joint J 2021;103-B(6 Supple A):177-184.

Renal Toxicity Associated With Resection and Spacer Insertion for Chronic Hip PJI.

BACKGROUND: Two-stage exchange arthroplasty with high-dose antibiotic-loaded bone cement spacer and intravenous (IV) antibiotics is the most common method of managing infected total hip arthroplasties. However, the contemporary incidence, risk factors, and outcomes of acute kidney injuries (AKIs) in this cohort are unknown. METHODS: We identified 227 patients treated with 256 antibiotic-loaded bone cement spacers after resection of an infected primary total hip arthroplasty between 2000 and 2017. Mean age was 65 years, mean body mass index was 30 mg/kg2, 55% were men, and 16% had pre-existing chronic kidney disease (CKD). Spacers were in situ for a mean of 15 weeks, concomitantly associated with IV or oral antibiotics for a mean of 6 weeks. AKI was defined as a creatinine ≥1.5X baseline or ≥0.3 mg/dL. Mean follow-up was 8 years. RESULTS: AKI occurred in 13 patients without pre-existing CKD (7%) vs 10 patients with CKD (28%; OR 5; P = .0001). None required acute dialysis. Postoperative fluid depletion (ß = 0.31; P = .0001), ICU requirement (ß = 0.40; P = .0001), and acute atrial fibrillation (ß = 0.43; P = .0001) were independent predictors for AKI in patients without pre-existing CKD. Duration of in situ spacer, mean antibiotic dose in cement, use of amphotericin B, and type of IV antibiotics were not significant risk factors. At last follow-up, 8 AKIs progressed to CKD, with one receiving dialysis 7 years later. CONCLUSION: AKIs occurred in 7% of patients with normal renal function, with 5-fold greater risk in those with CKD, and 4% did develop CKD. Importantly, causes of acute renal blood flow impairment were independent predictors for AKI. LEVEL OF EVIDENCE: Level III, comparative study.

Antistaphylococcal Penicillin vs Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Spinal Epidural Abscesses.

Cefazolin is commonly used as an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections; however, no study has compared these agents in MSSA spinal epidural abscess (SEA). We describe our experience in managing MSSA SEA and compare the clinical efficacy of cefazolin with ASPs. This retrospective multicenter study reviewed 79 adult patients diagnosed with SEA between January 2006 and July 2020 using data collected from electronic health records and clinical microbiology laboratory databases. Forty-five patients received cefazolin, while 34 received ASPs. The total antibiotic duration was longer in the ASPs group but not statistically significant. There were no significant differences in treatment failure at week 6 vs week 12, 30-day vs overall mortality, or in 90-day recurrence rates between the treatment groups. Cefazolin was equally as effective as ASPs, and our findings suggest that it can be an alternative to ASPs in the treatment of MSSA SEA.

Acute Kidney Injury When Treating Periprosthetic Joint Infections After Total Knee Arthroplasties with Antibiotic-Loaded Spacers: Incidence, Risks, and Outcomes.

BACKGROUND: Two-stage exchange arthroplasty with a high-dose antibiotic-loaded bone cement (ALBC) spacer and intravenous or oral antibiotics is the most common method of managing a periprosthetic joint infection (PJI) after a total knee arthroplasty (TKA). However, little is known about the contemporary incidence, the risk factors, and the outcomes of acute kidney injuries (AKIs) in this cohort. METHODS: We identified 424 patients who had been treated with 455 ALBC spacers after resection of a PJI following a primary TKA from 2000 to 2017. The mean age at resection was 67 years, the mean body mass index (BMI) was 33 kg/m2, 47% of the patients were women, and 15% had preexisting chronic kidney disease (CKD). The spacers (87% nonarticulating) contained a mean of 8 g of vancomycin and 9 g of an aminoglycoside per construct (in situ for a mean of 11 weeks). Eighty-six spacers also had amphotericin B (mean, 412 mg). All of the patients were concomitantly treated with systemic antibiotics for a mean of 6 weeks. An AKI was defined as a creatinine level of ≥1.5 times the baseline or an increase of ≥0.3 mg/dL within any 48-hour period. The mean follow-up was 6 years (range, 2 to 17 years). RESULTS: Fifty-four AKIs occurred in 52 (14%) of the 359 patients without preexisting CKD versus 32 AKIs in 29 (45%) of the 65 patients with CKD (odds ratio [OR], 5; p = 0.0001); none required acute dialysis. Overall, when the vancomycin concentration or aminoglycoside concentration was >3.6 g/batch of cement, the risk of AKI increased (OR, 1.9 and 1.8, respectively; p = 0.02 for both). Hypertension (ß = 0.17; p = 0.002), perioperative hypovolemia (ß = 0.28; p = 0.0001), and acute atrial fibrillation (ß = 0.13; p = 0.009) were independent predictors for AKI in patients without preexisting CKD. At the last follow-up, 8 patients who had sustained an AKI had progressed to CKD, 4 of whom received dialysis. CONCLUSIONS: In our study, the largest series to date that we are aware of regarding this issue, AKI occurred in 14% of patients with normal renal function at baseline, and 2% developed CKD after undergoing a 2-stage exchange arthroplasty for a PJI after TKA. However, the risk of AKI was fivefold greater in those with preexisting CKD. The causes of acute renal blood flow impairment were independent predictors for AKI. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Safety and Tolerability of Fluoroquinolones in Patients with Staphylococcal Periprosthetic Joint Infections.

BACKGROUND: Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown. METHODS: This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality. RESULTS: Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P < .001) in TKA infections. There was no significant difference in severe ADEs between FQ and non-FQ regimens in both THA and TKA infections. The overall rate of nonsevere ADEs in FQ compared with non-FQ regimens was 43.3% vs 6.1% (P < .001). FQs were associated with tendinopathy, myalgia, arthralgia, and nausea. CONCLUSIONS: A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs.

Automated Detection of Periprosthetic Joint Infections and Data Elements Using Natural Language Processing.

BACKGROUND: Periprosthetic joint infection (PJI) data elements are contained in both structured and unstructured documents in electronic health records and require manual data collection. The goal of this study is to develop a natural language processing (NLP) algorithm to replicate manual chart review for PJI data elements. METHODS: PJI was identified among all total joint arthroplasty (TJA) procedures performed at a single academic institution between 2000 and 2017. Data elements that comprise the Musculoskeletal Infection Society (MSIS) criteria were manually extracted and used as the gold standard for validation. A training sample of 1208 TJA surgeries (170 PJI cases) was randomly selected to develop the prototype NLP algorithms and an additional 1179 surgeries (150 PJI cases) were randomly selected as the test sample. The algorithms were applied to all consultation notes, operative notes, pathology reports, and microbiology reports to predict the correct status of PJI based on MSIS criteria. RESULTS: The algorithm, which identified patients with PJI based on MSIS criteria, achieved an f1-score (harmonic mean of precision and recall) of 0.911. Algorithm performance in extracting the presence of sinus tract, purulence, pathologic documentation of inflammation, and growth of cultured organisms from the involved TJA achieved f1-scores that ranged from 0.771 to 0.982, sensitivity that ranged from 0.730 to 1.000, and specificity that ranged from 0.947 to 1.000. CONCLUSION: NLP-enabled algorithms have the potential to automate data collection for PJI diagnostic elements, which could directly improve patient care and augment cohort surveillance and research efforts. Further validation is needed in other hospital settings. LEVEL OF EVIDENCE: Level III, Diagnostic.

Novel Use of Rifabutin and Rifapentine to Treat Methicillin-Resistant Staphylococcus aureus in a Rat Model of Foreign Body Osteomyelitis.

BACKGROUND: Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. METHODS: Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. RESULTS: Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. CONCLUSIONS: Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

Aseptic Reoperations Within 1 Year of Primary Total Knee Arthroplasty Markedly Increase the Risk of Later Periprosthetic Joint Infection.

BACKGROUND: Despite the high rate of success of primary total knee arthroplasty (TKA), some patients are candidates for early aseptic reoperation. The goal of this study is to evaluate the risk of subsequent periprosthetic joint infection (PJI) in patients treated with an aseptic reoperation within 1 year of primary TKA. METHODS: A retrospective review of our total joint registry compared 249 primary TKAs requiring an aseptic reoperation within 1 year following index arthroplasty to a control group of 17,867 TKAs not requiring reoperation within 1 year. Patients were divided into groups based on time from index TKA: (1) 90 days or less (114 TKAs) and (2) 91 to 365 days (135 TKAs). Mean age was 68 years with 57% female. Mean follow-up was 7 years. RESULTS: At 2 years postoperatively, patients undergoing an aseptic reoperation within 90 days subsequently had a 9% PJI rate, while patients undergoing an aseptic reoperation between 91 and 365 days subsequently had a 3% PJI rate. The control group had a 0.4% PJI rate. Compared to the control group, patients undergoing an aseptic reoperation within 90 days had an elevated risk of PJI (hazard ratio, 9; P < .0001), as did patients who had a reoperation between 91 and 365 days (hazard ratio, 4; P < .0001). CONCLUSION: Aseptic reoperation within 1 year of primary TKA was associated with a notably increased risk of subsequent PJI.