Identification of the causative organism(s) in periprosthetic joint infection (PJI) is a challenging task. The shortcomings of traditional cultures have been emphasized in recent literature, culminating in a clinical entity known as “culture-negative PJI.” Amidst the growing burden of biofilm infections that are inherently difficult to culture, the field of clinical microbiology has seen a paradigm shift from culture-based to molecular-based methods. These novel techniques hold much promise in the demystification of culture-negative PJI and revolutionization of the microbiology laboratory. This article outlines the clinical implications of culture-negative PJI, common causes of this diagnostic conundrum, established strategies to improve culture yield, and newer molecular techniques to detect infectious organisms.

Purpose The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. Methods We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008–June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12 months. Results A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d–11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10–12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12 months. 72.7% of patients were (very) satisfied with their care. Conclusion Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory.

Background Deep tissue culture specimens obtained at the time of revision shoulder arthroplasty are commonly positive for Cutibacterium . Clinical interpretation of positive cultures can be difficult. This was a multi-institutional study evaluating the accuracy of cultures for Cutibacterium using positive control (PC) and negative control (NC) samples. The relationship between time to culture positivity and strength of culture positivity was also studied. Methods Eleven different institutions were each sent 12 blinded samples (10 PC and 2 NC samples). The 10 PC samples included 2 sets of 5 different dilutions of a Cutibacterium isolate from a failed total shoulder arthroplasty with a probable periprosthetic infection. At each institution, the samples were handled as if they were received from the operating room. Specimen growth, time to culture positivity, and strength of culture positivity (based on semiquantitative assessment) were reported. Results A total of 110 PC samples and 22 NC samples were tested. One hundred percent of specimens at the 4 highest dilutions were positive for Cutibacterium . At the lowest dilution, 91% of samples showed positive findings. Cutibacterium grew in 14% of NC samples. Cutibacterium grew in PC samples at an average of 4.0 ± 1.3 days, and all of these samples showed growth within 7 days. The time to positivity was significantly shorter ( P < .001) and the strength of positivity was significantly higher ( P < .001) in true-positive cultures compared with false-positive cultures. Conclusions This multi-institutional study suggests that different institutions may report highly consistent rates of culture positivity for revision shoulder arthroplasty samples with higher bacterial loads. In contrast, with lower bacterial loads, the results are somewhat less consistent. Clinicians should consider using a shorter time to positivity and a higher strength of positivity as adjuncts in determining whether a tissue culture sample is a true positive.

Study Design: Systematic review. Objectives: Postoperative spinal implant infections (PSII) are an increasing challenge in the daily clinical routine. This review summarizes existing knowledge in the field of PSII, including definitions, epidemiology, classifications, risk factors, pathogenesis, symptoms, diagnosis, and treatment. Methods: A systematic review was performed using a structured PubMed analysis, based on the PRISMA criteria. The search terminology was set as: “spinal implant associated infection OR spinal implant infection OR spinal instrumentation infection OR peri spinal implant infection.” PubMed search was limited to the categories randomized controlled trials (RCT), clinical trials, meta-analysis and (systematic) reviews, whereas case reports were excluded. Studies from January 2000 to December 2020 were considered eligible. A total of 572 studies were identified, 82 references included for qualitative synthesis, and 19 for detailed sub analysis (12 meta-analysis, 7 prospective RCT). Results: Structural problems in the field of PSII were revealed, including (1) limited level of evidence in clinical studies (missing prospective RCT, metanalyzes), (2) small patient numbers, (3) missing standardized definitions, (4) heterogeneity in patient groups, and (5) redundancy in cited literature. Conclusion: Evidence-based knowledge about spinal implant-associated infections is lacking. All involved medical fields should come together to define the term PSII and to combine their approaches toward research, training, and patient care.

Background Although studies have demonstrated reductions in recurrent periprosthetic joint infection (PJI) with the administration of prolonged oral antibiotics at second-stage reimplantation, the potential for increasing bacterial resistance has not been studied. The purpose of this study was to determine if oral antibiotics at second-stage reimplantation increased the rate of antibiotic resistance in subsequent infections. Methods We retrospectively reviewed patients who underwent 2-stage exchange for chronic PJI from 2014 to 2019. We compared those who had received prolonged oral antibiotics at the time of stage 2 reimplantation with those who did not. The primary outcome was the presence of resistant organisms in any subsequent infection. The secondary outcome was the overall rate of recurrent PJI in the 2 groups. Multivariable analyses controlling for demographics and comorbid conditions were used. Results Of the 211 patients who underwent 2-stage exchange for PJI, 158 patients received prolonged oral antibiotics. The mean follow-up was 2.2 years. Recurrent PJI was diagnosed in 24 of 158 (15%) patients who received oral antibiotics compared with 11 of 53 (21%) patients who did not receive antibiotics (P = .35). PJI with resistant organisms was identified in 16 of 24 (67%) patients who received antibiotics compared with 0 of 11 (0%) patients who did not receive antibiotics (P = .0001). Conclusions Prolonged oral antibiotics following 2-stage exchange increase drug resistance to that antibiotic in subsequent PJI. We recommend further research in the area to refine antimicrobial protocols as we consider the risks and benefits of prolonged antibiotic treatment.

Background Long-term reinfection and mortality rates and clinical outcomes with sufficient subject numbers remain limited for patients undergoing two-stage exchange arthroplasty for chronic periprosthetic knee infections. The purpose of this study was to determine the long-term reinfection, complication, and mortality following reimplantation for two-stage exchange following knee arthroplasty. Methods Retrospective review of 178 patients who underwent two-stage exchange knee arthroplasty for chronic PJI at three large tertiary referral institutions with an average of 6.63-year follow-up from reimplantation from 1990 to 2015. Rates of reinfection, mortality, and all-cause revision were calculated along with the cumulative incidence of reinfection with death as a competing factor. Risk factors for reinfection were determined using Cox multivariate regression analysis. Results Overall rate of infection eradication was 85.41%, with a mortality rate of 30.33%. Patients with minimum 5-year follow-up (n = 118, average 8.32 years) had an infection eradication rate of 88.98%, with a mortality rate of 33.05%. Conclusion This is a large series with long-term follow-up evaluating outcomes of two-stage exchange knee arthroplasty resulting in adequate infection eradication and high mortality. Results were maintained at longer follow-up. This technique should be considered in patients with chronic PJI; however, realistic expectations regarding long-term outcomes must be discussed with patients.

Background: Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty (TJA). Rifampin is an antibiotic with the ability to penetrate bacterial biofilms, and thus has been considered as a potentially important adjunct in the prevention and treatment of PJI. The aim of this systematic review is to evaluate and summarize the use of rifampin in TJA, particularly in the context of PJI. Methods: A literature search of all relevant electronic databases was performed. All comparative studies assessing the use of rifampin in the context of TJA were included. Descriptive data are reported, and a meta-analysis was performed using all studies which compared the addition of rifampin to standard care in treating PJI. Results: A total of 33 studies met inclusion criteria. A meta-analysis of 22 studies comparing the addition of rifampin to standard care for treating PJI found a significant reduction in failure rates (26.0% vs 35.9%; odds ratio 0.61, 95% confidence interval 0.43-0.86). The protective effect of rifampin was maintained in studies which included exchange arthroplasty as a treatment strategy, but not in studies only using an implant retention strategy. Among studies reporting adverse events of rifampin, there was a 20.5% adverse event rate. Conclusion: Overall, rifampin appears to confer a protective effect against treatment failure following PJI. This treatment effect is particularly pronounced in the context of exchange arthroplasty. Further highlevel evidence is needed to clarify the exact indications and doses of rifampin which can most effectively act as an adjunct in the treatment of PJI.

Background: In preparation for surgery, patients being treated with disease-modifying antirheumatic drugs (DMARDs) are recommended to either continue or withhold therapy perioperatively. Some of these drugs have known effects against bone healing, hence the importance of adequately managing them before and after surgery. Objective: We aim to assess the current evidence for managing conventional synthetic and/or biologic DMARDs in the perioperative period for elective spine surgery. Methods: A systematic review of four databases was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The included manuscripts were methodically scrutinized for quality, postoperative infections, wound healing characteristics, bone fusion rates, and clinical outcomes. Results: Six studies were identified describing the management of conventional synthetic and/or biologic DMARDs. There were 294 DMARD-treated patients described undergoing various spine surgeries such as craniovertebral junction fusions. Three of the studies involved exclusive continuation of DMARDs in the perioperative window; one study involved exclusive discontinuation of DMARDs in the perioperative window; and two studies involved continuation or discontinuation of DMARDs perioperatively. Of patients that continued DMARDs in the perioperative period, 13/50 patients (26.0%) had postoperative surgical site infections or wound dehiscence, 2/19 patients (10.5%) had delayed wound healing, and 32/213 patients (15.0%) had secondary revision surgeries. A fusion rate of 14/19 (73.6%) was described in only one study for patients continuing DMARDs perioperatively. Conclusions: The available published data may suggest a higher risk of wound healing concerns and lower than average bone fusion, although this may be under-reported given the current state of the literature.

Background Peri-prosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Determining the optimal duration of intravenous (IV) antibiotics for PJI managed with debridement and implant retention (DAIR) is a research priority. Methods Patients undergoing DAIR for early and late-acute PJI of the hip or knee were randomised to receive 2 (short-course) or 6 (standard-course) weeks of IV antibiotics, with both groups completing 12 weeks of antibiotics in total. The primary endpoint of this pilot, open-label, randomised trial was a 7-point ordinal desirability of outcome ranking (DOOR) score, which accounted for mortality, clinical cure and treatment adverse events at 12 months. Duration of IV treatment was used as a tiebreaker, with shorter courses ranked higher. Outcome adjudication was performed by expert clinicians blinded to the allocated intervention (Australia and New Zealand Clinical Trials Registry ACTRN12617000127303). Results 60 patients were recruited; 31 and 29 were allocated to short- and standard-course treatment, respectively. All had an evaluable outcome at 12 months and were analysed by intention-to-treat. Clinical cure was demonstrated in 44 (73%) overall; 22 (71%) in the short-course group and 22 (76%) in the standard-care group (P=0.77). Using the DOOR approach, the probability that short- was better than standard-course treatment was 59.7% (95% confidence interval 45.1-74.3). Conclusions In selected patients with early and late-acute PJI managed with DAIR, shorter courses of IV antibiotics may be appropriate. Due to small sample size, these data accord with, but do not confirm, results from other international trials of early transition to oral antibiotics.

Introduction Periprosthetic joint infection (PJI) is a devastating complication in orthopaedic and trauma surgery, which puts a high burden on the patients involving recurrent hospitalisation, prolonged courses of antibiotic medication, severe pain and long periods of immobility as well as high levels of psychological distress. Thus, this multicentre study aims at implementing body-oriented psychotherapy in clinical practice and evaluating its therapeutic effect on the quality of life. Methods and analysis A prospective, parallel two-armed randomised controlled trial with approximately n=270 patients with verified PJI treated surgically with a one-staged exchange, or a two-staged exchange will be conducted. Functional relaxation (FR) therapy will be implemented as a group therapy. FR originally belongs to the psychodynamically based body-oriented psychotherapy. Intervention techniques consist of minute movements of small joints, which are performed during relaxed expiration accompanied by an exploration of differences of body feelings. A group will include 3–8 patients, led by a specialist physiotherapist certified in FR once a week. The participants are consecutively admitted to the class and participate in 12 sessions. The control group will consist of patients receiving an unspecific ‘placebo relaxation’ intervention for the same duration. The primary efficacy endpoint is the mental component summary and physical component summary of quality of life assessed by the 36-Item Short Form Health Survey (SF-36) after 6 months. Secondary outcomes include SF-36 scores after 12 months, consumption of pain medication, mobility measured by the Parker mobility score and the physical activity measured by daily steps with an accelerometer (actibelt). Ethics and dissemination Approval from the Ethical Committee of the University Hospital Regensburg was received (file number: 21-2226-101). Written, informed consent to participate will be obtained from all participants. Results will be made available in the form of peer-reviewed publications and presentation in congresses. Trial registration number DRKS00028881; German Clinical Trials Register.

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.

Abstract Background Rifampin is generally advised in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin remains a matter of debate. We evaluated the outcome of patients treated with and without rifampin, and analyzed the influence of timing, dose and co-antibiotic. Methods Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death or the need for suppressive antimicrobial treatment. Results A total of 669 patients were analyzed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P &lt; .001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P &lt; .001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 – 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone or clindamycin (OR 10.1, 95% CI 5.65 – 18.2) and the start of rifampin within 5 days after surgical debridement (OR 1.96, 95% CI 1.08 – 3.65) were predictors of treatment failure. The dosing of rifampin had no effect on outcome. Conclusions Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged, but requires further investigation.

Study Design. A prospective single center observational study. Objectives. The aim of this study was to examine the potential role of sonication in the diagnosis of low-grade infections and its association with pedicle screw (PS) loosening, and to describe risk factors and radiological findings associated with spinal implant infection. Summary of Background Data. Although PS loosening has mainly been attributed to mechanical overload, implant colonization and biofilm formation have recently been suggested. Culturing of sonication fluid implants is promising in the field of spine instrumentation infection, but little data are available. Methods. We prospectively included all patients who were subjected to implant removal. PS loosening was assessed with computed tomography (CT) scan. Different clinical and radiological parameters which could serve as indicators of implant infection were studied. Results. Thirty-eight patients were included in the study and 11 of them (29%) had a positive sonication result. Patients with spinal implant infection were associated with screw loosening (P= 0.005). Particularly, those screws with a positive microbiological culture showed signs of screw loosening in the preoperative CT scan (P< 0.001). Our results also showed that radiological screw loosening at L1-L3 level, and loosened larger constructs were associated with screw microbial colonization. The most common isolated microorganisms were coagulase-negative staphylococci and Cutibacterium acnes. An implant-based multivariate analysis indicated that screw loosening, the absence of prophylactic cefazolin, ICU hospitalization, screw breakage, and L1-L3 spine level were independent risk factors for implant-associated infection. Our model exhibited a high predictive power with an area under the curve of 0.937. Conclusion. As clinical presentation of deep implant chronic infection is unspecific, consideration of these factors enables preoperative prediction and risk stratification of implant colonization, thus helping patient's management.

BACKGROUND: Bundles have shown to improve patient outcomes in several settings. Surgical site infections (SSIs) following joint replacement surgery are associated with severe outcomes. We aimed to determine the effectiveness of non-pathogen specific bundled interventions in reducing SSIs after hip arthroplasty procedures. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted according to the PRISMA statement guidelines (PROSPERO registration number CRD42020203031). PubMed, Embase and Cochrane databases were searched for studies evaluating SSI prevention bundles in hip replacement surgery, excluding studies evaluating pathogen-specific bundles. Records were independently screened by two authors. The primary outcome was the SSI rate in intervention and control groups or before and after bundle implementation. Secondary outcomes of interest were bundle compliance and the number and type of bundle components. A meta-analysis was conducted using raw data, by calculating pooled relative risk (RR) SSI estimates to assess the impact of bundled interventions on SSI reduction. RESULTS: Eleven studies were included in the qualitative review and four studies comprising over 20 000 patients were included in the quantitative synthesis. All included studies found bundles were associated with reduced SSI rates. The pooled RR estimated from the fixed-effects model was 0.76 (95% confidence interval 0.61-0.96, p 0.022) with 49.8% heterogeneity. CONCLUSIONS: Results support the effectiveness of non-pathogen specific bundled interventions in preventing SSIs following hip arthroplasty. A "core" group of evidence-based elements for bundle development were identified.

BACKGROUND In patients with diabetic foot osteomyelitis (DFO) who underwent surgical debridement, we investigated whether a short (3 weeks), compared with a long (6 weeks) duration of systemic antibiotic treatment is associated with non-inferior results for clinical remission and adverse events (AE). METHODS In this prospective, randomized, non-inferiority, pilot trial, we randomized (allocation 1:1), patients with DFO after surgical debridement to either a 3-week or a 6-week course of antibiotic therapy. The minimal duration of follow-up after end of therapy was two months. We compared outcomes using Cox regression and non-inferiority analyses (25% margin, power 80%). RESULTS Among 93 enrolled patients (18% females; median age 65 years), 44 were randomized to the 3-week arm and 49 to the 6-week arm. The median number of surgical debridement was 1 (range, 0-2 interventions). In the intention-to-treat (ITT) population, remission occurred in 37 (84%) of the patients in the 3-week arm compared to 36 (73%) in the 6-week arm (p=0.21). The number of AE was similar in the two study arms (17/44 vs. 16/49; p=0.51), as were the remission incidences in the per-protocol (PP) population (33/39 vs. 32/43; p=0.26). In multivariate analysis, treatment with the shorter antibiotic course was not significantly associated with remission (for the ITT population, hazard ratio 1.1, 95%CI 0.6-1.7; for the PP population hazard ratio 0.8, 95%CI 0.5-1.4). CONCLUSIONS In this randomized, controlled pilot trial, a post-debridement systemic antibiotic therapy course for DFO of 3-weeks gave similar (and statistically non-inferior) incidences of remission and AE to a course of 6 weeks.

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.

Diabetic foot ulcers are a common complication of poorly controlled diabetes and often become infected, termed diabetic foot infection. There have been numerous studies of the microbiology of diabetic foot infection but no meta-analysis has provided a global overview of these data. This meta-analysis aimed to investigate the prevalence of bacteria isolated from diabetic foot infections using studies of any design which reported diabetic foot infection culture results.

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.