Implementation and validation of a Bayesian method for accurately forecasting duration of optimal pharmacodynamic target attainment with dalbavancin during long-term use for subacute and chronic staphylococcal infections.

Dalbavancin is increasingly being used for long-term treatment of subacute and chronic staphylococcal infections. In this study, a new Bayesian model was implemented and validated using MwPharm software for accurately forecasting the duration of pharmacodynamic target attainment above the efficacy thresholds of 4.02 mg/L or 8.04 mg/L against staphylococci. Forecasting accuracy improved substantially with the a posteriori approach compared with the a priori approach, particularly when two measured concentrations were used. This strategy may help clinicians to estimate the duration of optimal exposure with dalbavancin in the context of long-term treatment.

Silver-Coated Distal Femur Megaprosthesis in Chronic Infections with Severe Bone Loss: A Multicentre Case Series.

Periprosthetic joint infections (PJI) and fracture-related infections (FRI) of the distal femur (DF) may result in massive bone defects. Treatment options include articulated silver-coated (SC) megaprosthesis (MP) in the context of a two-stage protocol. However, there is limited evidence in the literature on this topic. A retrospective review of the prospectively maintained databases of three Institutions was performed. Forty-five patients were included. The mean follow-up time was 43 ± 17.1 months. Eight (17.8%) patients had a recurrent infection. The estimated recurrence-free survival rate was 91.1% (93.5% PJI vs. 85.7% FRI) 2 years following MP implantation, and 75.7% (83.2% PJI vs. 64.3% FRI; p = 0.253) after 5 years. No statistically relevant difference was found according to the initial diagnosis (PJI vs. FRI). Among possible risk factors, only resection length was found to significantly worsen the outcomes in terms of infection control (p = 0.031). A total of eight complications not related to infection were found after reimplantation, but only five of them required further surgery. Above-the-knee amputation was performed in two cases (4.4%), both for reinfection. Articulated DF SC MP in a two-stage protocol is a safe and effective treatment for chronic knee infection with severe bone loss.

Pharmacokinetic and pharmacodynamic considerations for optimizing antimicrobial therapy used to treat bone and joint infections: an evidence-based algorithmic approach.

INTRODUCTION: Bone and joint infections (BJIs) are a major health concern causing remarkable morbidity and mortality. However, which antimicrobial treatment could be the best according to specific clinical scenarios and/or to the pharmacokinetic/pharmacodynamic (PK/PD) features remains an unmet clinical need. This multidisciplinary opinion article aims to develop evidence-based algorithms for empirical and targeted antibiotic therapy of patients affected by BJIs. AREAS COVERED: A multidisciplinary team of four experts had several rounds of assessment for developing algorithms devoted to empirical and targeted antimicrobial therapy of BJIs. A literature search was performed on PubMed-MEDLINE (until April 2023) to provide evidence for supporting therapeutic choices. Four different clinical scenarios were structured according to specific infection types (i.e. vertebral osteomyelitis, prosthetic joint infections, infected non-unions and other chronic osteomyelitis, and infectious arthritis), need or not of surgical intervention or revision, isolation or not of clinically relevant bacterial pathogens from blood and/or tissue cultures, and PK/PD features of antibiotics. EXPERT OPINION: The proposed therapeutic algorithms were based on a multifaceted approach considering the peculiar features of each antibiotic (spectrum of activity, PK/PD properties, bone penetration rate, and anti-biofilm activity), and could be hopefully helpful in improving clinical outcome of BJIs.

Management of periprosthetic joint infection of shoulder arthroplasty: Single-stage versus two-stage protocols. A systematic review and meta-analysis of the literature.

Background: The treatment of shoulder prosthetic joint infections (PJIs) requiring removal of the prosthesis is not well defined. This article aims to systematically review and compare the results of the literature in single-stage and two-stage protocols in the treatment of shoulder PJI. Methods: An in-depth search on PubMed/Scopus/Web of Science databases and cross-referencing search was carried out concerning the articles reporting detailed data on the topic. Results: A total of 486 shoulder PJIs were included: 137 treated with single-stage and 349 with two-stage procedure. A similar distribution between early and not-early infections (19.1% vs 80.9%) was found between the two groups. The overall rate of success in terms of PJI eradication was significantly higher in the single-stage group (95.6% vs 85.7%, p < 0.001). The non-infection-related complications rate was 13.8% in the single-stage group and 37.6% in the two-stage group (p < 0.001), the non-infection-related revision rate was 8% and 18.9%, respectively (p = 0.005). Discussion: The single-phase protocol showed a higher success rate in eradicating the infection and a lower complication rate. However, the low number of patients included, the low quality of the articles, the lack of data on clinical severity and bacteriological virulence suggest caution in conclusions.

A descriptive case series of the relationship between maintenance of conservative PK/PD efficacy thresholds of dalbavancin over time and clinical outcome in long-term treatment of staphylococcal osteoarticular infections.

OBJECTIVE: To describe the relationship between maintenance of pharmacokinetic/pharmacodynamic (PK/PD) dalbavancin efficacy thresholds over time and clinical outcome in a case series of patients who underwent therapeutic drug monitoring (TDM) during long-term treatment of staphylococcal osteoarticular infections (OIs). METHODS: Patients who received two 1500-mg doses of dalbavancin 1 week apart for documented staphylococcal OIs, underwent TDM assessment, and had clinical outcome assessable at follow-up were included retrospectively. Dalbavancin concentrations ≥4.02 and/or ≥8.04 mg/L were identified as conservative PK/PD efficacy thresholds. The percentage of time of the overall treatment period with dalbavancin concentrations above these efficacy thresholds was calculated and correlated with clinical outcome. RESULTS: In total, 17 patients were included in this study. Long-term dalbavancin was used mainly for treating prosthetic joint infections (9/17, 52.9%). In 13/17 patients (76.5%), clinical outcome was assessable after at least 6 months of follow-up and was always successful (100.0%). In four of 17 patients (23.5%), clinical outcome is favourable after 3.7, 4.8, 5.1 and 5.3 months of follow-up, respectively. In most patients, both dalbavancin PK/PD efficacy thresholds were reached for most of the treatment period (%time ≥4.02 mg/L: 100% in 13 cases, 75-99.9% in two cases, 50-74.99% in two cases; %time ≥8.04 mg/L: 100% in eight cases, 75-99.9% in four cases, 50-74.99% in four cases, <50% in one case). CONCLUSIONS: These findings could support the idea that maintenance of conservative PK/PD efficacy thresholds of dalbavancin for the majority of the treatment period may represent a valuable approach in dealing efficaciously with long-term treatment of staphylococcal OIs.

Which Patients with Chronic Periprosthetic Joint Infection Are Less Suitable to Successful Two Stage Exchange Arthroplasty Surgery? A Retrospective Clinical Trial.

BACKGROUND: Two-stage exchange (TSE) arthroplasty is currently considered the gold standard for chronic periprosthetic joint infections (PJIs), despite a failure rate reported in up to 10% of patients. Little is known about the risk factors that may compromise successful TSE arthroplasty management in such patients. The main purpose of the current study was to highlight the potential risk factors of patients with chronic PJIs after THA managed by implant removal, outlining the differences between reimplanted patients and those that were never reimplanted because of a non-eradicated infection. METHODS: We conducted a retrospective observational study of patient candidates for TSE arthroplasty surgery, managed at the authors' institution, over a four-year timeframe. The data were retrieved from the hospital's information database. The enrolled population was divided into two Groups: A, reimplanted; B, non-reimplanted because of a non-eradicated infection within one year. For each Group, demographic information, PJI-related risk factors, type of pathogen and presence of single or polymicrobial infection, were collected and analyzed. RESULTS: In total, 21 patients were included in the study, 14 patients in Group A and 7 in Group B. Major Depression (p = 0.049) and polymicrobial infection (p = 0.04) were more commonly observed in patients that were not reimplanted in the study period. No differences between the two groups were observed when other characteristics were compared. CONCLUSIONS: Patients with major depression, or those hosting polymicrobial periprosthetic hip infections, are more susceptible to failure of TSE arthroplasty procedures for chronic PJIs, hampering THA reimplantation. Current findings may drive further research and contribute to the understanding of the role of these risk factors in chronic PJI patients.

Population pharmacokinetics and Monte Carlo simulation for dosage optimization of fosfomycin in the treatment of osteoarticular infections in patients without renal dysfunction.

Background: Fosfomycin is gaining interest in the treatment of complex osteoarticular infections (OI) due to MDR pathogens.Objective: The aims were to conduct population pharmacokinetics of fosfomycin in a cohort of OI patients receiving 16g/daily by intermittent (II) or continuous infusion (CI), and to carry out Monte Carlo simulations for dosage optimization in the treatment of these infections.Methods: Patients underwent blood sampling on day 5 of therapy (2-3 serial samples). Population pharmacokinetics and Monte Carlo simulations were performed to define the probability of target attainment (PTA) of 70% T>MIC, and the cumulative fraction of response (CFR) against common OI pathogens with dosages of 8, 12, 16, and 20g/day administered by II, extended-infusion (EI) or CI.Results: Forty-eight patients were recruited. A two-compartment open model with infusion input and first-order elimination was developed. Estimated creatinine clearance (CLCR) was included as covariate in the final model. Monte Carlo simulations showed that optimal PTAs and CFRs (≥90%) may be achieved in three different classes of renal function by administering a daily dosage of: 2g q6h by II against S. aureus, E. coli, ESBL-producing E. Coli and MRSA; 8g by CI against CoNS, K. pneumoniae and ESBL-producing K. pneumoniae; 12g by CI against P. aeruginosa, and 16g by CI against KPC-producing K. pneumoniae Conclusion: Our study provides a strong rationale for considering fosfomycin dosages of 8-16 g daily by CI in several clinical scenarios for OI patients. Feasibility of administration by CI in an elastomeric pump makes fosfomycin a candidate for OPAT programs.

Population pharmacokinetics of dalbavancin and dosing consideration for optimal treatment of adult patients with staphylococcal osteoarticular infections.

Background: Dalbavancin is gaining interest in the treatment of complex osteoarticular (OA) infections.Objective: To conduct a population pharmacokinetic analysis of dalbavancin in a prospective cohort of adult patients with Gram-positive OA infections and to identify optimal dosing regimens for long term-treatment.Methods: Non-linear mixed-effects modelling was performed with Monolix. Monte Carlo simulations were performed with six dalbavancin regimens (1500mg at day 1; 1000mg at day 1 plus 500mg at day 8; 1500mg at day1 and 8; 1500mg at day1 and 8 plus 500, 1000 or 1500mg at day 36) to assess the PTA of three pharmacodynamic target of fAUC24h/MIC against S. aureus (>27.1, 53.3 and 111.1). Cumulative fraction of response (CFR) was calculated against MIC distribution of both MRSA and MSSA as well. Desirable PTAs and CFRs were ≥90%.Results: Fifteen patients provided 120 plasma concentrations. Most (73.3%) had prosthetic joint infections. Clinical cure rate was 87%. A two-compartment model with linear elimination well described the data. No covariate was retained in the final model. Pharmacokinetic dalbavancin estimates were 0.106L/h for CL and 36.4L for Vss The tested dosing regimens granted desirable CFRs against S. aureus at the most effective PK/PD target for a period ranging 3-to-9 weeks. Conclusion: Giving a two 1500mg dosing regimen of dalbavancin one week apart may ensure efficacy against both MSSA and MRSA up to 5 weeks in patients with OA infections. Clinical assessment at that time may allow for considering whether or not an additional dose should be administered for prolonging effective treatment.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

INTRODUCTION: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. METHODS: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. RESULTS: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. CONCLUSIONS: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, registration no. NCT03826108.

Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient's quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

Oral Versus Standard Antimicrobial Treatment for Pyogenic Native Vertebral Osteomyelitis: A Single-Center, Retrospective, Propensity Score-Balanced Analysis.

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.

Synchronous Periprosthetic Joint Infections: A Scoping Review of the Literature.

Prosthetic joint infections (PJIs) occurring in multiple joints at the same time (synchronous PJI) are an extremely rare complication, frequently associated with bacteremia, and are associated with high mortality rates. The presence of three or more prosthetic joints, rheumatoid arthritis, neoplasia, bacteremia and immune-modulating therapy seem to be the recurring risk factors for synchronous PJI. In case of PJIs, all other replaced joints should be considered as potentially infected and investigated if PJI is suspected. Treatments of synchronous multiple PJIs vary and must be decided on a case-by-case basis. However, the advantages of one-stage exchange seem to outweigh the two-stage protocol, as it decreases the number of necessary surgical procedures. Nonetheless, too few studies have been conducted to allow firm conclusions about the best handling of synchronous PJI. Thus, additional studies are needed to understand this devastating complication and to design the most appropriate diagnostic and therapeutic path.

Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug Monitoring.

A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration−time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.

Spine Infections: The Role of Fluorodeoxyglucose Positron Emission Tomography (FDG PET) in the Context of the Actual Diagnosis Guideline.

Spondylodiscitis is an infectious process that requires numerous health care professionals to be clearly diagnosed and eventually successfully treated. It implies a variety of microbiological agents and conditions; during the diagnostic workup, it is difficult to correctly identify them, and the clinician has to rapidly choose the correct treatment to avoid permanent injuries to the patient. In this context, we conducted a review to better understand the most suitable use of Positron Emission Tomography with 18-Fluoro-deossi-glucose (FDG PET) in a patient suspected of spondylodiscitis, based on current guidelines and literature.. We wanted to review the role of FDG PET in the spondylodiscitis diagnosis and follow up in the context of the current guidelines.

Epidemiology of Fungal Periprosthetic Joint Infection: A Systematic Review of the Literature.

Fungal prosthetic joint infection (fPJI) is a rare complication; nonetheless, it represents a significant diagnostic and therapeutic challenge. There are no official guidelines on the most effective approach to identify and treat fPJIs. This systematic review aims to review the current literature on fPJI management and provide a comprehensive overview of this topic, especially from an epidemiologic point of view. Studies eligible for this systematic review were identified through an electronic systematic search of PubMed, Scopus, and Web of Science until 30 September 2022. Further references were obtained by cross-referencing. Sixty-three studies met the inclusion criteria, reporting on 372 cases of fPJI; such cases were described mostly in case reports and small case series with only a few larger cohort studies. Diagnosis of fPJI is challenging because of its chronic and indolent clinical course; it is further complicated by the technical difficulty of harvesting fungal cultures. A two-stage revision was the primary procedure in 239 (64.2%) patients whereas DAIR and one-stage approaches were reported in 30 (8.0%) and 18 (4.8 %) cases. In conclusion, our study highlights the heterogeneity of the reported treatments of fPJI, particularly in terms of medical management. With concern to a surgical approach, a two-stage revision arthroplasty is generally suggested, considering fPJI a delayed or late infection. The need for multicenter, prospective studies to provide standardized protocols and improve the treatment of fungal PJI clearly emerges.

Bone and Joint Infections: The Role of Imaging in Tailoring Diagnosis to Improve Patients' Care.

Imaging is needed for the diagnosis of bone and joint infections, determining the severity and extent of disease, planning biopsy, and monitoring the response to treatment. Some radiological features are pathognomonic of bone and joint infections for each modality used. However, imaging diagnosis of these infections is challenging because of several overlaps with non-infectious etiologies. Interventional radiology is generally needed to verify the diagnosis and to identify the microorganism involved in the infectious process through imaging-guided biopsy. This narrative review aims to summarize the radiological features of the commonest orthopedic infections, the indications and the limits of different modalities in the diagnostic strategy as well as to outline recent findings that may facilitate diagnosis.

White Blood Cell Count Is the Most Reliable Test for the Diagnosis of Septic Arthritis After Anterior Cruciate Ligament Reconstruction: An Observational Study of 38 Patients.

PURPOSE: (1) To evaluate the diagnostic testing performance of the synovial white blood cell (WBC) count, polymorphonuclear cell percentage, and synovial glucose, synovial protein, synovial lactate dehydrogenase, and synovial C-reactive protein levels as diagnostic markers for the diagnosis of septic arthritis after anterior cruciate ligament (ACL) reconstruction; (2) to define the ideal thresholds of the aforementioned tests, leading to the optimal sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy; and (3) to define the sensitivity of synovial fluid culture and synovial tissue sample culture, as well as determine whether previous antibiotic treatment may affect the accuracy of these tests. METHODS: We performed a retrospective analysis of all patients readmitted from January 2009 to September 2019 with signs suggestive of septic arthritis and undergoing a knee aspiration for synovial fluid analysis and culture. The receiver operating characteristic curve and the associated area under the curve were constructed for the aforementioned synovial markers. Sensitivity, specificity, PPV, NPV, and accuracy were calculated for the obtained optimal values. Sensitivity was also calculated for synovial fluid culture and synovial tissue sample culture, and the influence of previous antibiotic treatments on culture sensitivity was evaluated. RESULTS: Among 3,408 cases of ACL reconstruction, after the exclusion of 13 patients not meeting the inclusion criteria, 24 infected and 14 uninfected patients were reviewed and included in the analysis. The diagnosis was confirmed by the presence of 2 positive culture findings with the same isolated microorganism or at least 3 of the 4 following criteria: elevated serum C-reactive protein level and erythrocyte sedimentation rate, positive results of histologic analysis of synovial tissue, macroscopic evidence of purulence, and 1 positive culture finding. The receiver operating characteristic curve analysis showed that the most reliable marker for the diagnosis of septic arthritis after ACL reconstruction was the synovial WBC count (area under the curve, 0.89). A cutoff value of 28,100 cells/mL presented the highest accuracy (0.85), highest PPV (0.94), and highest NPV (0.76); moreover, with the threshold set at 40,000 cells/mL, postoperative infection could be diagnosed with 100% specificity. The sensitivity of synovial fluid culture was significantly lower than the sensitivity of synovial tissue sample culture (0.63 vs 0.96, P = .0045); moreover, the sensitivity further decreased if patients took antibiotics before aspiration (0.44 vs 0.73), although this decrease was not statistically significant. CONCLUSIONS: The synovial WBC count is the most reliable test for the diagnosis of septic arthritis after ACL reconstruction. Although the sensitivity of synovial fluid culture is affected by previous antibiotic treatment, the synovial WBC count is not influenced and proves to be useful in the diagnosis of this uncommon complication. LEVEL OF EVIDENCE: Level II, diagnostic study.

Correction to: Silver-coated (PorAg®) endoprosthesis can be protective against reinfection in the treatment of tumor prostheses infection.

The original version of this article unfortunately contained a mistake. The correct information is given below.

Silver-coated (PorAg®) endoprosthesis can be protective against reinfection in the treatment of tumor prostheses infection.

INTRODUCTION: We aim to evaluate the use of silver (PorAg®) coated compared to uncoated prosthesis in two-stage revision for prosthetic joint infection (PJI) of distal femur and proximal tibia megaprosthesis in oncological patients. MATERIALS AND METHODS: In total, 68 patients were retrospectively evaluated. Median age was 30 years (range 14-83). In total, 29 patients were re-implanted with PorAg® prosthesis and 39 with uncoated prosthesis (Megasystem C®, Waldemar Link GmbH & Co. KG, Hamburg, Germany). All patients had PJI confirmed according to Musculoskeletal Infection Society (MSIS) criteria. In 10 cases, no microorganism was identified at the time of first-stage revision, but all had a sinus communicating with the prosthesis. Successful eradication of the infection was defined by the absence of clinical/serologic evidence of infection at 6 months after the second stage or at latest follow-up. Infection was again defined according to the MSIS criteria. RESULTS: At 3-year follow-up, estimated reinfection rate in the silver group was slightly lower than in uncoated EPR (10.3% vs. 17.5%, p = 0.104). Among reinfected patients, only one out of three patients (33%) in the silver group required an amputation compared to 80% in the nonsilver group (p = 0.047). CONCLUSIONS: Our results show the efficacy of PorAg® coating in the two-stage revision of knee EPR. PorAg®-coated EPR may have possible advantages over this traditional strategy, in particular when applied to patients with a higher risk of reinfection.

[Bacterial and fungal urinary tract infections: epidemiology, pathogenesis and clinical management]. / Infezioni batteriche e micotiche delle vie urinarie: epidemiologia, patogenesi e gestione clinica.

Urinary tract infections (UTIs) are the most common bacterial infections and represent a significant problem both from an epidemiological and clinical point of view. Moreover, they place a substantial financial burden on society. UTIs can be asymptomatic or symptomatic and are characterized by a wide spectrum of symptoms ranging from mild irritative voiding to bacteremia, sepsis, severe sepsis or septic shock. They may occur in a normal genitourinary tract with no prior instrumentation (uncomplicated infections) or in genitourinary tracts with structural or functional abnormalities, or in patients with specific risk factors (complicated infections). In the hospital setting bacterial and fungal UTIs are strongly related to the use and misuse of indwelling urinary catheters. Catheter-related UTIs increase morbidity, mortality and costs and constitute an efficient reservoir for multidrug-resistant bacteria.