Abstract Background The Oral Versus Intravenous Antibiotics (OVIVA) Trial demonstrated that oral therapy, when used during the initial 6 weeks in the treatment in bone and joint infection (BJI), is noninferior to intravenous therapy. To date there are no reports describing reproducibility of these findings in a real-world setting. Methods We studied all patients diagnosed with BJI at our hospital 12 months pre- and postimplementation of the OVIVA trial findings into clinical practice. An infection consultant recommended antibiotic treatment and patients were followed up by an outpatient parenteral antibiotic therapy (OPAT) service. Prospective data from a local registry was used to analyze baseline clinical details, outcome, length of hospital stay (LOS), and costs. Results A cohort of 328 patients (145 pre- and 183 postimplementation) was analyzed. Postimplementation, 66.1% of patients were switched to a suitable oral antibiotic regimen. Definite failure at 1 year was 13.6% in the preimplementation group and 18.6% in the postimplementation group (P = .154). Postimplementation, definite failure was more common in patients requiring intravenous antibiotics due to lack of suitable oral options (intravenous, 26.7% and oral, 14.3%). Adverse drug reactions (ADRs) requiring closer monitoring or change to treatment were more common postimplementation (21.0% and 37.1%, respectively). ADR-related hospital readmissions were similar in both groups (2.1 and 2.2%). Comparing both groups, the postimplementation group showed a reduction of 4 days in the median LOS and a median cost reduction of £2764.28 per patient. Conclusions The OVIVA trial findings can be safely implemented into clinical practice when patients on oral antibiotics are followed up by an established OPAT service. Two-thirds of patients were switched to a suitable oral antibiotic regimen. Implementation led to reductions in hospital LOS and antibiotic costs.

BACKGROUND: Debridement, antibiotics and implant retention (DAIR) is the treatment of choice for acute postoperative and acute hematogenous periprosthetic joint infection (PJI). There is limited literature on predictive prognostic factors for DAIR. We aim to report the outcomes of DAIR and investigate the predictive prognostic factors. METHODS: We retrospectively reviewed 106 DAIRs. Failure was defined as requiring removal of TKA implants. Predictive factors that may influence success of DAIR treatment such as age, gender, body mass index, ethnicity, American Society of Anesthesiologists score, comorbidities, preoperative erythrocyte sedimentation rate (ESR) and C-reactive protein, symptom duration, time between total knee arthroplasty and DAIR, cultures, rifampicin use, polyethylene liner change, and antibiotic duration were analyzed. RESULTS: The success rate of DAIR was 69.8% (74/106 patients). For successes, mean time from DAIR-to-mortality was longer than failures (61.6 ± 42.7 vs 9.75 ± 9.60 months, P = .0150). Methicillin-susceptible Staphylococcus aureus PJI (odds ratio [OR] 3.64, confidence interval [CI] 1.30-10.2, P = .0140) was a significant predictor for failure of DAIR. Higher preoperative ESR correlated to failure (OR 1.02, CI 1.01-1.04, P = .008). In successes, mean ESR was 75.4 (66.1-84.6), whereas mean ESR in failures was 116 (88.3-143) (P = .011). An ESR > 107.5 predicted failure with a sensitivity of 51.5 and specificity of 85.2. ESR > 107.5 correlated to failure (OR 6.60, CI 2.29-19.0, P < .001). Repeat DAIRs were strongly correlated to failure (OR 5.27, CI 1.99-13.9, P < .01). CONCLUSION: DAIR failure is associated with earlier time to mortality. Repeat DAIRs, elevated ESR > 107.5, and S aureus PJI are associated with treatment failure and 2-stage revision is recommended.

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 &lt; .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 &lt; .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.

Background: Fungal prosthetic joint infections (PJIs) are rare, especially those caused by non-Candida species. Treatment has not been fully elucidated, since a plethora of antifungal and surgical interventions have been proposed. Τhis study represents an effort to clarify the optimal management of non-Candida fungal PJIs, by reviewing all relevant published cases. Methods: A thorough review of all existing non-Candida fungal PJIs in the literature was conducted. Data regarding demographics, responsible organisms, antifungal treatment (AFT), surgical intervention, time between initial arthroplasty and onset of symptoms, and time between onset of symptoms and firm diagnosis, as well as the infection’s outcome, were evaluated. Results: Forty-two PJIs, in patients with mean age of 66.2 years, were found and reviewed. Aspergillus spp. were isolated in most cases (10; 23.8%), followed by Coccidioides spp. (7; 16.7%) and Pichiaanomala (5; 11.9%). Fluconazole was the preferred antifungal regimen (20 cases; 47.6%), followed by amphotericin B (18 cases; 42.9%), while the mean AFT duration was 9.4 months (SD = 7.06). Two-stage revision arthroplasty (TSRA) was performed in 22 cases (52.4%), with the mean time between stages being 5.2 months (SD = 2.9). The mean time between initial joint implantation and onset of symptoms was 42.1 months (SD = 50.7), while the mean time between onset of symptoms and diagnosis was 5.8 months (SD = 14.3). Conclusions: Non-Candida fungal PJIs pose a clinical challenge, demanding a multidisciplinary approach. The present review has shown that combination of TSRA separated by a 3–6-month interval and prolonged AFT has been the standard of care in the studied cases.

Background Prosthetic joint infection (PJI) is a potentially limb-threatening complication of total knee arthroplasty. Phage therapy is a promising strategy to manage such infections including those involving antibiotic-resistant microbes, and to target microbial biofilms. Experience with phage therapy for infections associated with retained hardware is limited. A 62-year-old diabetic man with a history of right total knee arthroplasty 11 years prior who had suffered multiple episodes of prosthetic knee infection despite numerous surgeries and prolonged courses of antibiotics, with progressive clinical worsening and development of severe allergies to antibiotics, had been offered limb amputation for persistent right prosthetic knee infection due to Klebsiella pneumoniae complex. Intravenous phage therapy was initiated as a limb-salvaging intervention. Methods The patient received 40 intravenous doses of a single phage (KpJH46Φ2) targeting his bacterial isolate, alongside continued minocycline (which he had been receiving when he developed increasing pain, swelling, and erythema prior to initiation of phage therapy). Serial cytokine and biomarker measurements were performed before, during, and after treatment. The in vitro anti-biofilm activity of KpJH46Φ2, minocycline and the combination thereof was evaluated against a preformed biofilm of the patient’s isolate and determined by safranin staining. Results Phage therapy resulted in resolution of local symptoms and signs of infection and recovery of function. The patient did not experience treatment-related adverse effects and remained asymptomatic 34 weeks after completing treatment while still receiving minocycline. A trend in biofilm biomass reduction was noted 22 hours after exposure to KpJH46Φ2 (P = .063). The addition of phage was associated with a satisfactory outcome in this case of intractable biofilm-associated prosthetic knee infection. Pending further studies to assess its efficacy and safety, phage therapy holds promise for treatment of device-associated infections.

BACKGROUND: Surgical and host factors predispose patients to periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). While surgical factors are modifiable, host factors can be challenging, and there are limited data demonstrating that preoperative patient optimization decreases risk of PJI. The goal of this study was to evaluate whether extended oral antibiotic prophylaxis reduces the one-year infection rate in high-risk patients. METHODS: A total of 3855 consecutive primary THAs and TKAs performed between 2011 and 2019 at a suburban academic hospital with modern perioperative and infection-prevention protocols were retrospectively reviewed. Beginning in January 2015, a 7-day oral antibiotic prophylaxis protocol was implemented after discharge for patients at high risk for PJI. The percentage of high-risk patients diagnosed with PJI within 1 year was compared between groups that did and did not receive extended antibiotic prophylaxis. Univariate and logistic regression analyses were performed, with P ≤ .05 denoting statistical significance. RESULTS: Overall 1-year infection rates were 2.26% and 0.85% after THA and TKA, respectively. High-risk patients with extended antibiotic prophylaxis had a significantly lower rate of PJI than high-risk patients without extended antibiotic prophylaxis (0.89% vs 2.64%, respectively; P < .001). There was no difference in the infection rate between high-risk patients who received antibiotics and low-risk patients (0.89% vs 1.29%, respectively; P = .348) with numbers available. CONCLUSION: Extended postoperative oral antibiotic prophylaxis for 7 days led to a statistically significant and clinically meaningful reduction in 1-year infection rates of patients at high risk for infection. In fact, the PJI rate in high-risk patients who received antibiotics was less than the rate seen in low-risk patients. Thus, extended oral antibiotic prophylaxis may be a simple measure to effectively counteract poor host factors. Moreover, the findings of this study may mitigate the incentive to select healthier patients in outcome-based reimbursement models. Further study with a multicenter randomized control trial is needed to further validate this protocol. LEVEL OF EVIDENCE: Therapeutic level III.

BACKGROUND The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes.

Aims The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition. Methods This paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance. Results This process evolved a three-level approach to the diagnostic continuum, resulting in a definition set and guidance, which EBJIS, MSIS, and ESGIAI have fully endorsed. Conclusion The definition presents a novel three-level approach to diagnosis, based on the most robust evidence, which will be useful to clinicians in daily practice. Cite this article: Bone Joint J 2021;103-B(1):18–25.

Background Periprosthetic joint infection (PJI) is one of the most feared complications of total joint arthroplasty (TJA). Although commonly the result of colonization by Staphylococcal species, a growing number of cases of PJI with fungal pathogens have been reported within the last decade. Although standard treatment with two-stage exchange mirrors that of bacterial PJI, the variability in virulence between fungal species makes for an unpredictable and challenging treatment course. Methods A review of Pubmed and Scopus from years 2009 to 2019 was conducted with the search terms fungal, infection, Candida, arthroplasty, periprosthetic, and prosthesis. Publications were reviewed and screened, yielding data for 286 patients with fungal PJI in the hip, knee, shoulder, and elbow prosthetics. Results Patient comorbidities generally included conditions impairing wound healing and immune response such as diabetes mellitus. Candida species were the most common fungal pathogens identified (85%); 30% had a concomitant bacterial infection. A two-stage exchange was most utilized, with a mean success rate of 65%. Antifungal impregnated spacers were utilized in 82 cases, with a comparatively high success rate (81%). Attempts at debridement with implant retention had substantially lower cure rates (15%). Conclusions Two-stage exchange is the favored approach to treating fungal PJI. Debridement with implant retention does not appear adequate to control infection, and retrieval of implanted materials should be prioritized. The use of antifungal impregnated spacers is an important area of ongoing research, with uncertainty regarding the type and quantity of antifungal agent to incorporate, although recent reports support the use of these agents.

Background Periprosthetic joint infection (PJI) in total knee arthroplasty (TKA) is a challenging problem. The purpose of this study was to outline a novel technique to treat TKA PJI. We define 1.5-stage exchange arthroplasty as placing an articulating spacer with the intent to last for a prolonged time. Methods A retrospective review was performed from 2007 to 2019 to evaluate patients treated with 1.5-stage exchange arthroplasty for TKA PJI. Inclusion criteria included: articulating knee spacer(s) remaining in situ for 12 months and the patient deferring a second-stage reimplantation because the patient had acceptable function with the spacer (28 knees) or not being a surgical candidate (three knees). Thirty-one knees were included with a mean age of 63 years, mean BMI 34.4 kg/m2, 12 were female, with a mean clinical follow-up of 2.7 years. Cobalt-chrome femoral and polyethylene tibial components were used. We evaluated progression to second-stage reimplantation, reinfection, and radiographic outcomes. Results At a mean follow-up of 2.7 years, 25 initial spacers were in situ (81%). Five knees retained their spacer(s) for some time (mean 1.5 years) and then underwent a second-stage reimplantation; one of the five had progressive radiolucent lines but no evidence of component migration. Three knees (10%) had PJI reoccurrence. Four had progressive radiolucent lines, but there was no evidence of component migration in any knees. Conclusions 1.5-stage exchange arthroplasty may be a reasonable method to treat TKA PJI. At a mean follow-up of 2.7 years, there was an acceptable rate of infection recurrence and implant durability.

Background: Prosthetic joint infection (PJI) is a significant cause of morbidity and mortality following knee replacement surgery. The diagnosis can be challenging and is based on a combination of clinical suspicion, radiographic findings and also biochemical/ microbiological investigations. Our Aim was to review the role of aspiration and biopsy in the diagnosis of PJI in Total Knee Arthroplasty (TKA). Method/results: Aspirated synovial fluid should be analysed by direct culture, via blood culture bottles, EDTA bottles for cell count and ‘point of care’ testing such as leucocyte esterase or alpha defensin. Synovial WCC and PMN cell percentage are important steps in diagnosis of both acute and chronic PJI. A minimum of 5 deep samples using a 5 clean instrument technique should be obtained and sent for tissue culture done either blind or arthroscopic. Formal fluoroscopic guided interface biopsy has also been described with excellent results. In a recent series of 86 TKRs preoperative arthroscopic biopsy group had a sensitivity of 100%, specificity of 94.7%, positive predictive value of 87.4% and a negative predictive value of 100%. Conclusion: In the presence of clinical suspicion with raised biomarkers, it is recommended that aspiration +/- biopsy with synovial fluid testing is performed. Direct culture and cell count are recommended. ‘Point of care tests’ such as Leucocyte Esterase testing should be considered. Duration of culture, including pathogen and host factors, should be discussed with a local microbiology/ID department in the context of a formal multidisciplinary team.

Background Total joint arthroplasty (TJA) is considered one of the most successful surgical procedures ever developed. It can successfully provide pain relief, restore joint function, and improve mobility and quality of life. Prosthetic joint infection (PJI) presents with a wide variety and severity of signs and symptoms. It remains a major threat to the outcome of TJA procedures and usually necessitates surgical intervention and prolonged courses of antibiotics. Inappropriate treatment of an unrecognized PJI usually ends with unacceptable and sometimes catastrophic results. The aim The understanding and evaluation of diagnostic investigations are extremely important to properly diagnose PJI, including frequently unrecognized low-grade infections, and to provide healthcare professionals with needed information for the care of patients affected by this condition. This article aims to review most of the methods available in PJI diagnostics, to emphasize the strengths and the weaknesses of each of them, and to provide a guideline on how to select the surgical treatment strategy based on the level of diagnostic certainty during the evaluation period. To safely accomplish this, it is crucial to be aware of the limitations of each diagnostic modality. The focus The emphasis will be on the use and interpretation of the core criteria for PJI diagnosis, including the pathognomonic sinus tract communicating with the implant, purulent synovial fluid, inflammation in the periprosthetic tissue, cell count with differential, microbial growth in the synovial fluid culture, tissue sample cultures, and sonication samples.