Background Suppressive antibiotic therapy (SAT) after total joint arthroplasty (TJA) debridement, antibiotics, and implant retention (DAIR) maximizes reoperation-free survival. Our aims were to evaluate SAT after DAIR of acutely infected primary TJA regarding: 1) adverse drug reaction (ADR)/intolerance; 2) reoperation for infection; and 3) antibiotic resistance. Methods Patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA) DAIR for acute PJI at two academic medical centers from 2015 to 2020 were identified (n = 115). Data were collected on patient demographics, infecting organisms, antibiotics, ADR/intolerances, reoperations, and antibiotic resistances. Median SAT duration was 11 months. Stepwise multivariate logistic regressions were used to identify covariates significantly associated with outcomes of interest. Results There were 11.1% and 16.3% of TKA and THA DAIR patients, respectively, who had ADR/intolerance to SAT. Patients prescribed trimethoprim/sulfamethoxazole (TMP-SMZ) (P = 0.0014) or combination antibiotic therapy (P = 0.0169) after TKA DAIR had increased risk of ADR/intolerance. There was no difference in reoperation-free survival between TKA (83.3%) and THA (65.1%) DAIR (P = 0.5900) at mean 2.8-year follow-up. Risk of reoperation for infection was higher among TKA Staphylococcus aureus infections (P = 0.0004) and lower with increased SAT duration (P < 0.0450). The optimal duration of SAT was nearly 2 years. No cases of antibiotic resistance developed due to SAT. Conclusion One should consider SAT after TJA DAIR due to improved reoperation-free survival and favorable safety profile. Prolonged SAT did not induce antibiotic resistance. Use TMP-SMZ with caution because of the increased likelihood of ADR/intolerance.

Introduction Periprosthetic joint infection (PJI) is a common source of failure following elbow arthroplasty. Perioperative prophylactic antibiotics are considered standard of care. However, there are no data regarding the comparative efficacy of various antibiotics in the prevention of PJI for elbow arthroplasty. Previous studies in shoulder, hip, and knee arthroplasty have demonstrated higher rates of PJI with administration of non-cefazolin antibiotics. The elbow has higher rates of PJI than other joints. Therefore, this study evaluated whether perioperative antibiotic choice affects rates of PJI in elbow arthroplasty. Materials & Methods A single institution prospectively collected Total Joint Registry database was queried to identify patients who underwent primary elbow arthroplasty between 2003 and 2021. Elbows with known infection prior to arthroplasty (25) and procedures with incomplete perioperative antibiotic data (7) were excluded, for a final sample size of 603 total elbow arthroplasties and 19 distal humerus hemiarthroplasties. Cefazolin was administered in 561 elbows (90%) and non-cefazolin antibiotics including vancomycin (32 elbows, 5%), clindamycin (27 elbows, 4%) and piperacillin/tazobactam (2 elbows, 0.3%) were administered in the remaining 61 elbows (10%). Univariate and multivariate analyses were conducted to determine the association between the antibiotic administered and the development of PJI. Infection-free survivorship was estimated using the Kaplan-Meier (KM) method. Results Deep infection occurred in 47 elbows (7.5%) and 16 elbows (2.5%) were diagnosed with superficial infections. Univariate analysis demonstrated that patients receiving non-cefazolin alternatives were at significantly higher risk for any infection (Hazard Ratio (HR) 2.6, 95% confidence interval [CI] 1.4-5.0]; p < 0.01) and deep infection (HR 2.7 [95% CI 1.3 – 5.5]; p < 0.01) compared with cefazolin administration. Multivariable analysis, controlling for several independent predictors of PJI (tobacco use, male sex, surgical indication other than osteoarthritis, and American Society of Anesthesiologists score), showed that non-cefazolin administration had a higher risk for any infection (HR 2.8 [CI 1.4 – 5.3]; p < 0.01) and deep infection (HR 2.9 [95% CI 1.3 – 6.3]; p < 0.01). Survivorship free of infection was significantly higher at all time points for the cefazolin cohort (Figure 1). Discussion In primary elbow arthroplasty, cefazolin administration was associated with significantly lower rates of PJI compared to non-cefazolin antibiotics, even in patients with a greater number of prior surgeries which is known to increase the risk of PJI. For patients with penicillin or cephalosporin allergies, preoperative allergy testing or a cefazolin test dose should be considered prior to administering non-cefazolin alternatives.

Background This study aimed to identify the success rate of debridement, antibiotics, and implant retention (DAIR) for prosthetic joint infection (PJI) in a large prospective cohort of patients undergoing total knee arthroplasty (TKA). The ability for different PJI classification systems to predict success was assessed. Methods Prospective data recorded in the Prosthetic Joint Infection in Australia and New Zealand Observational study were analyzed. One hundred eighty-nine newly diagnosed knee PJIs were managed with DAIR between July 2014 and December 2017. Patients were prospectively followed up for 2 years. A strict definition of success was used, requiring the patient being alive with documented absence of infection, no ongoing antibiotics and the index prosthesis in place. Success was compared against the Coventry (early PJI ≤1 month), International Consensus Meeting (early ≤90 days), Auckland (early <1 year), and Tsukayama (early ≤1 month, hematogenous >1 month with <7 days symptoms, chronic >1 month with >7 days symptoms) classifications. Results DAIR success was 45% (85/189) and was highest in early PJIs defined according to the Coventry (adjusted odds ratio [aOR] = 3.9, P = .01), the International Consensus Meeting (aOR = 3.1, P = .01), and the Auckland classifications (aOR = 2.6, P = .01). Success was lower in both hematogenous (aOR = 0.4, P = .03) and chronic infections (aOR = 0.1, P = .003). Conclusion Time since primary TKA is an important predictor of DAIR success. Success was highest in infections occurring <1 month of the primary TKA and progressively decreased as time since the primary TKA increased.

Objectives The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection during follow-up compared with controls with a negative SFC. Methods This retrospective multicentre observational study was performed within the European Study Group of Implant-Associated Infections. All patients who underwent revision surgery of a prosthetic joint between 2013 and 2019 and had a minimum follow-up of 1 year were included. Patients with positive tissue cultures or synovial fluid cultures were excluded from the study. Results A total of 95 cases (positive SFC) and 201 controls (negative SFC) were included. Infection during follow-up occurred in 12 of 95 cases (12.6%) versus 14 of 201 controls (7.0%) (p = 0.125). In all, 79.8% of cases were with treated with antibiotics (76/95). Of the non-treated cases, 89% (17/19) had a positive SFC with a low virulent microorganism. When solely analysing patients who were not treated with antibiotics, 16% of the cases (3/19) had an infection during follow-up versus 5% of the controls (9/173) (p = 0.08). Discussion Although not statistically significant, infections were almost twice as frequent in patients with an isolated positive SFC. These findings require further exploration in larger trials and to conclude about the potential benefit of antibiotic treatment in these cases.

Background Diagnosing periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) remains challenging despite recent advancements in testing and evolving criteria over the last decade. Moreover, the effects of antibiotic use on diagnostic markers are not fully understood. Thus, this study sought to determine the influence of antibiotic use within 48 hours before knee aspiration on synovial and serum laboratory values for suspected late PJI. Methods Patients who underwent a TKA and subsequent knee arthrocentesis for PJI workup at least 6 weeks after their index arthroplasty were reviewed across a single healthcare system from 2013 to 2020. Median synovial white blood cell (WBC) count, synovial polymorphonuclear (PMN) percentage, serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), and serum WBC count were compared between immediate antibiotic and nonantibiotic PJI groups. Receiver operating characteristic (ROC) curves and Youden’s index were used to determine test performance and diagnostic cutoffs for the immediate antibiotics group. Results The immediate antibiotics group had significantly more culture-negative PJIs than the no antibiotics group (38.1 versus 16.2%, P = .0124). Synovial WBC count demonstrated excellent discriminatory ability for late PJI in the immediate antibiotics group (area under curve, AUC = 0.97), followed by synovial PMN percentage (AUC = 0.88), serum CRP (AUC = 0.86), and serum ESR (AUC = 0.82). Conclusion Antibiotic use immediately preceding knee aspiration should not preclude the utility of synovial and serum lab values for the diagnosis of late PJI. Instead, these markers should be considered thoroughly during infection workup considering the high rate of culture-negative PJI in these patients.

BACKGROUND CONTEXT The rate of surgical site infection (SSI) following elective spine surgery ranges from 0.5%‒10%. Published reports suggest a higher SSI rate in non-elective spine surgery such as spine trauma; however, there is a paucity of large database studies examining this issue. PURPOSE The objective of this study was to investigate the incidence and risk factors of SSI in patients undergoing spine surgery for thoracic and lumbar fractures in a large population database. STUDY DESIGN/SETTING This is a retrospective study utilizing the PearlDiver Patient Claims Database. PATIENT SAMPLE Patients undergoing spine surgery for thoracic and lumbar fractures between 2015-2020 were identified in the PearlDiver Patient Claims Database using ICD-10 codes. Patients were excluded who had another surgery either 14 days before or 21 days after the index spine surgery, or pathologic fracture. OUTCOME MEASURES Rate of surgical site infection. METHODS Clinical data collected from the PearlDiver database based on ICD-10 codes included gender, age, diabetes, smoking status, obesity, Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index (CCI), and SSI. Univariate analysis was used to assess the association of potential risk factors and SSI. Multivariable analysis was used to identify independent risk factors of SSI. The authors have no conflicts of interest or funding sources to declare. RESULTS A total of 11,401 patients undergoing spine surgery for thoracic and lumbar fractures met inclusion criteria, and 1,065 patients were excluded. 860 patients developed SSI (7.5%). Risk factors significantly associated with SSI in univariate analysis included diabetes (OR 1.50; 95% CI, 1.30‒1.73; p<.001), obesity (OR 1.66; 95% CI, 1.44‒1.92; p<.001), increased age (p<.001), ECI (p<.001), and CCI (p<.001). On multivariable analysis, obesity and ECI were independently associated with SSI (p<.001 and p<.001, respectively). CONCLUSIONS Non-elective surgery for thoracic and lumbar fractures is associated with a 7.5% risk of SSI. Obesity and ECI are independent predictors of SSI in this population. Limitations include the reliance on accurate insurance coding which may not fully capture all SSI, and in particular superficial SSI. These findings provide a broad overview of the risk of SSI in this population at a national level and may also help counsel patients regarding risk.

Whether rifampin benefits retained staphylococcal prosthetic joint infection is unsettled. In a meta-analysis of 8 studies, we found greater clinical cure with fluoroquinolone-rifampin vs all other regimens (odds ratio [OR], 2.68; 95% CI, 1.43–5.02), but no greater cure with other rifampin combinations vs regimens without rifampin (OR, 1.22; 95% CI, 0.79–1.88).

Background Image-guided biopsies in patients with suspected native vertebral osteomyelitis (NVO) are recommended to establish the microbiological diagnosis and guide antibiotic therapy. Despite recent advances, the microbiological yield of this procedure remains between 48% and 52%. A better understanding of factors associated with this low yield may lead to improved microbiological diagnosis. Methods We retrospectively identified patients with suspected NVO undergoing image-guided biopsies from January 2011 to June 2021 at our institution. Two hundred nine patients undergoing 248 percutaneous biopsies were included. Demographic data, biopsy and microbiologic techniques, clinical characteristics, and antibiotic use were collected. Multivariable logistic regression analysis was conducted to determine factors associated with microbiological yield. Results A total of 110 of 209 (52.6%) initial image-guided biopsies revealed positive microbiological results. This number increased to 121 of 209 (57.9%) when repeat image-guided biopsies were included. In multivariable analysis, aspiration of fluid was associated with a 3-fold increased odds of yielding a positive result (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.39–7.04; P = .006), whereas prior antibiotic use was associated with a 3-fold decreased yield (OR, 0.32; 95% CI, .16–.65; P = .002). A univariate subgroup analysis revealed a significant association between the length of the antibiotic-free period and microbiological yield, with the lowest rates of pathogen detection at 0–3 days and higher rates as duration increased (P = .017). Conclusions Prior antibiotic use in patients with suspected NVO was associated with a decrease in the microbiological yield of image-guided biopsies. An antibiotic-free period of at least 4 days is suggested to maximize yield. Successful fluid aspiration during the procedure also increases microbiological yield.

Recent data suggest that oral therapy can be effective for bone infections. We aim to assess the efficacy of an early switch to oral therapy (<2 weeks) compared to a non-early switch in bacterial native vertebral osteomyelitis. We conducted a cohort study at Mayo Clinic, Rochester (MN), between 2019–2021 combined with a systematic review, which queried multiple databases. Data were analyzed using a random-effects model. The cohort study included 139 patients: two received an early switch. Of 3708 citations, 13 studies were included in the final analysis. Meta-analysis demonstrated no difference in treatment failure (odds ratio = 1.073, 95 % confidence interval 0.370–3.116), but many studies presented high risk of bias. Current evidence is insufficient to conclude the proportion of patients with failure or relapse is different in the two groups. High-quality studies are warranted before early switch can be routinely recommended.

Objectives To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. Design Pragmatic, parallel group, open label, randomised controlled trial. Setting High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. Participants 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). Interventions A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. Main outcome measures The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups. Results The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval −8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4). Conclusions At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery.

Introduction: Culture-negative (CN) prosthetic joint infections (PJIs) account for approximately 10 % of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJIs within a large prospective cohort study, comparing their characteristics and outcomes with culture-positive (CP) cases. Methods: The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, multicentre observational cohort study that was conducted at 27 hospitals between 2014 and 2017. We compared baseline characteristics and outcomes of all patients with CN PJI from the PIANO cohort with those of CP cases. We report on PJI diagnostic criteria in the CN cohort and apply internationally recognized PJI diagnostic guidelines to determine optimal CN PJI detection methods. Results: Of the 650 patients with 24-month outcome data available, 55 (8.5 %) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female (32 (58.2 %) vs. 245 (41.2 %); p = 0.016), involve the shoulder joint (5 (9.1 %) vs. 16 (2.7 %); p = 0.026), and have a lower mean C-reactive protein (142 mg L−1 vs. 187 mg L−1; p = 0.016). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (adjusted odds ratio, aOR, of 3.78 and 95 %CI of 1.65–8.67). Suboptimal diagnostic sampling was common in both cohorts, with CN PJI case detection enhanced using the Infectious Diseases Society of America PJI diagnostic guidelines. Conclusions: Current PJI diagnostic guidelines vary substantially in their ability to detect CN PJI, with comprehensive diagnostic sampling necessary to achieve diagnostic certainty. Definitive surgical management strategies should be determined by careful assessment of infection type, rather than by culture status alone.

Background The optimal duration of antibiotic therapy after debridement and implant retention (DAIR) for periprosthetic joint infections (PJIs) is debated. Furthermore, the best antibiotic regimens for staphylococcal PJI are also unclear. In this study, we evaluated the impact of antibiotic therapy duration on the risk of failure. We assessed the utility of rifampin-based regimens for staphylococcal PJI managed with DAIR. Methods We performed a retrospective cohort study of patients 18 years and older diagnosed with hip and knee PJI who underwent DAIR between January 1, 2008 and 31 December 31, 2018 at Mayo Clinic, USA. The outcome was failure of DAIR. For statistical analysis, joint-stratified Cox regression models adjusted for age, sinus tract, symptom duration, and primary/revision arthroplasty were performed. Results We examined 247 cases of PJI with a median follow-up of 4.4 years (interquartile range [IQR], 2.3–7) after DAIR. The estimated 5-year cumulative incidence of failure was 28.1% (n = 65). There was no association between the duration of intravenous (IV) antibiotics (median 42 days; IQR, 38–42) and treatment failure (P = .119). A shorter duration of subsequent oral antibiotic therapy was associated with a higher risk of failure (P = .005; eg, 90-day vs 1-year duration; hazard ratio [HR], 3.50; 95% confidence interval [CI], 1.48–8.25). For staphylococcal knee PJI, both the use and longer duration of a rifampin-based regimen were associated with a lower risk of failure (both P = .025). There was no significant association between fluoroquinolone (FQ) use and failure (HR, 0.62; 95% CI, .31–1.24; P = .172). Conclusions The duration of initial IV antibiotic therapy did not correlate with treatment failure in this cohort of patients. Rifampin use is recommended for staphylococcal knee PJI. There was no apparent benefit of FQ use in staphylococcal PJI.

Background Interest in shorter antimicrobial regimens and oral treatment for osteoarticular infections is growing. The aim of this study is to assess whether there is an association between the administration of an entirely oral antibiotic therapy (OT) and the clinical outcome of native vertebral osteomyelitis (NVOs). Methods We conducted a single-center, retrospective, observational study on consecutive patients with pyogenic NVOs over a 10-year period (2008–2018). We performed multivariate logistic regression analysis to identify risk factors for clinical failure, both in the whole population and in subgroups. The impact of OT versus standard treatment (intravenous induction followed by oral treatment whenever possible) was assessed in patients with a non-multidrug-resistant microorganism (MDRO) etiology, and the impact of a rifampin-containing regimen was assessed in patients affected by NVOs caused by staphylococci or of unknown etiology. Results The study population included 249 patients, and 33 (13.3%) experienced clinical failure; the OT group consisted of 54 patients (21.7%). Multivariate regression analysis of the whole population selected Charlson comorbidity index (adjusted odds ratio [aOR], 1.291; 95% confidence interval [CI], 1.114–1.497; P = .001) and MDRO etiology (aOR, 3.301; 95% CI, 1.368–7.964; P = .008) as independent factors for clinical failure. Among patients affected by a non-MDRO NVO, OT was not associated with an increased risk of clinical failure (aOR, 0.487; 95% CI, .133–1.782; P = .271), even after adjustment for the propensity score of receiving OT. In the subgroup of patients with staphylococcal or unknown etiology, NVO rifampin was independently associated with favorable outcome (aOR, 0.315; 95% CI, .105–.949; P = .040). Conclusions An entirely oral, highly bioavailable treatment, including rifampin, may be as effective as parenteral treatment in selected patients with NVOs.

This international, multi-center study investigated the effect of individual components of surgery on the clinical outcomes of patients treated for fracture-related infection (FRI). All patients with surgically treated FRIs, confirmed by the FRI consensus definition, were included. Data were collected on demographics, time from injury to FRI surgery, soft tissue reconstruction, stabilization and systemic and local anti-microbial therapy. Patients were followed up for a minimum of one year. In total, 433 patients were treated with a mean age of 49.7 years (17–84). The mean follow-up time was 26 months (range 12–72). The eradication of infection was successful in 86.4% of all cases and 86.0% of unhealed infected fractures were healed at the final review. In total, 3.3% required amputation. The outcome was not dependent on age, BMI, the presence of metalwork or time from injury (recurrence rate 16.5% in FRI treated at 1–10 weeks after injury; 13.1% at 11–52 weeks; 12.1% at >52 weeks: p = 0.52). The debridement and retention of a stable implant (DAIR) had a failure rate of 21.4%; implant exchange to a new internal fixation had a failure rate of 12.5%; and conversion to external fixation had a failure rate of 10.3% (adjusted hazard ratio (aHR) DAIR vs. Ext Fix 2.377; 95% C.I. 0.96–5.731). Tibial FRI treated with a free flap was successful in 92.1% of cases and in 80.4% of cases without a free flap (HR 0.38; 95% C.I. 0.14–1.0), while the use of NPWT was associated with higher recurrence rates (HR 3.473; 95% C.I. 1.852–6.512). The implantation of local antibiotics reduced the recurrence from 18.7% to 10.0% (HR 0.48; 95% C.I. 0.29–0.81). The successful treatment of FRI was multi-factorial. These data suggested that treatment decisions should not be based on time from injury alone, as other factors also affected the outcome. Further work to determine the best indications for DAIR, free flap reconstruction and local antibiotics is warranted.

Little is known about the clinical use of antifungal-loaded acrylic bone cement in the treatment of periprosthetic hip and knee joint infections (PJIs). Hence, we performed a literature search using PubMed/MEDLINE from inception until December 2021. Search terms were “cement” in combination with 13 antifungal agents. A total of 10 published reports were identified, which described 11 patients and 12 joints in which antifungal-loaded cement was employed. All studies were case reports or case series, and no randomized controlled trials were identified. In 6 of 11 patients, predisposing comorbidities regarding the emergence of a fungal PJI were present. The majority of the studies reported on infections caused by Candida species. In six cases (seven joints), the cement was solely impregnated with an antifungal, but no antibiotic agent (amphotericin B, voriconazole, and fluconazole). In the other five joints, the cement was impregnated with both antibiotic(s) and antifungals. Great discrepancies were seen regarding the exact loading dose. Four studies investigated the local elution of antifungal agents in the early postoperative period and observed a local release of antifungals in vivo. We conclude that there is a paucity of data pertaining to the clinical use of antifungal-loaded bone cement, and no studies have assessed the clinical efficacy of such procedures. Future studies are urgently required to evaluate this use of antifungals in PJI.

Accurate diagnosis of orthopedic infection is crucial in guiding both antimicrobial therapy and surgical management in order to optimize patient outcomes. A variety of microbiological and nonmicrobiological methods are used to establish the presence of a musculoskeletal infection. In this minireview, we examine traditional culture-based and newer molecular methodologies for pathogen detection, as well as systemic and localized assays to assess host response to maximize diagnostic yield.