Passerini, Matteo

Abstract Background Dalbavancin is increasingly used off-label for chronic Gram-positive bone and joint infections (BJIs) requiring prolonged antimicrobial therapy, but optimal dosing strategies and the role of therapeutic drug monitoring (TDM) remain unclear. We evaluated the real-world implementation of a proactive TDM-guided dalbavancin workflow within an outpatient parenteral antimicrobial therapy (OPAT) programme. Methods Single-centre prospective observational implementation study including adult patients with BJIs consecutively treated with dalbavancin in OPAT service between July 2022 and August 2025. A multidisciplinary team developed a workflow incorporating TDM-guided pharmacokinetic modelling to individualize dosing intervals after fixed initial administrations (Days 1, 8 and 43). Target Cmin concentrations were ≥8 mg/L, later increased to ≥15 mg/L after European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint revision. Primary outcomes included implementation metrics (feasibility, fidelity and appropriateness). Secondary outcomes were clinical effectiveness, safety and overall workflow success. Results The workflow was applied to 101 patients accounting for 418 TDM-guided dalbavancin administrations (feasibility). Three patient-driven treatment discontinuations were observed (3/101, 3.0%), and scheduled administrations occurred within the predefined time window in 335/418 (83.5%) of cases (fidelity). Pharmacological target attainment was achieved in 285/342 (89.6%) of administrations without dosing delays (appropriateness). Clinical effectiveness was achieved in 55/73 (75.3%) patients completing therapy, with 28/101 (28%) still on treatment. Adverse events–related discontinuation occurred in 3/101 (3%) patients. Overall workflow success was observed in 74/101 (73.2%) patients. Conclusions A multidisciplinary TDM-guided dalbavancin workflow within an OPAT programme was feasible and safe, achieving high target attainment and favourable clinical outcomes. This approach supports individualized long-acting dalbavancin therapy for complex chronic BJIs.

Abstract Background Prosthetic joint infection (PJI) represents an important complication of total joint arthroplasty, affecting approximately 2% of patients. However, considerable heterogeneity in outcome definitions renders cross-study and clinical comparisons challenging. Methods We performed a meta-epidemiological study and systematic review of cohort studies and randomized controlled trial (RCTs) reporting clear definitions of PJI outcomes. Relevant data regarding outcome definitions of treatment success or failure were extracted and categorized into 7 outcome domains: clinical signs and symptoms, imaging, microbiology, mortality, antibiotics-related, surgical-related, and histology. A network plot was generated to visualize domains combinations. Data on patient-reported outcome measures (PROMs) were also collected. Based on these results, we finally proposed a working definition of PJI core outcome set. Results The literature search identified 7585 references, leading to 461 studies. The majority were retrospective (416/461, 90.2%), with limited representation of prospective studies (37/461, 8.0%) and RCTs (8/461, 1.7%). Outcome reporting was highly heterogeneous, with the clinical criterion being the most frequently used domain, combined with microbiological, surgical, and mortality-related outcomes. In contrast, histopathological, imaging, and antibiotic-related criteria were rarely reported. Thirty-six PROMs were included in only 111 (24.1%) studies, most commonly the Knee Society Score (26%) and Harris Hip Score (23%). Conclusions We showed substantial heterogeneity in PJI outcome definitions, with inconsistent reporting across key domains, limiting comparability and evidence synthesis. Standardized, consensus-based outcomes incorporating patient-reported and antibiotic-related measures are needed, and the proposed core outcome set may support harmonized research and clinical practice aligned with the new PJI definition.

Background Bacterial infections remain a major global health burden, causing significant morbidity and mortality. Despite ongoing advances, prompt diagnosis is still hampered by nonspecific host biomarkers and the inherently slow turnaround of traditional microbiological cultures. These limitations often delay the initiation of appropriate treatments. In recent years, affinity-based proteomic approaches have been explored to address this gap. Among them, the Proximity Extension Assay (PEA) has emerged as a promising multiplexed protein quantification tool, capable of simultaneously measuring hundreds of immune and inflammatory proteins with high sensitivity from minimal sample volumes. Such technologies hold the potential to identify novel biomarkers, thereby improving both diagnosis and patient management in bacterial infections. Main body In this systematic scoping review, we examined studies applying PEA-based proteomics to adult bacterial infections. Out of the records screened, ten studies met inclusion criteria. Most were conducted in Europe and North America, relied primarily on plasma samples, and employed commercially available panels enriched for immune and inflammatory mediators. Study quality varied, with some evidence of variability and potential risk of bias. Across the 379 proteins investigated, a subset of proteins were consistently associated with bacterial infections across multiple clinical contexts, whereas others showed limited or no associations. Conclusions Current applications of PEA-based proteomics in adult bacterial infections is limited and largely exploratory. Rather than supporting immediate clinical translation, the available evidence suggests the value of PEA-based approaches for informing biomarker discovery. Future research should prioritize well-designed, longitudinal, and pathogen-stratified studies in clinically relevant settings to strengthen evidence robustness and support the rational development of proteomics-informed diagnostic and translational strategies.

Abstract Background A unified definition of prosthetic joint infection outcomes (PJI) is crucial for consistent data, study comparisons, and better care. This study systematically reviews how PJIs outcomes are defined, building on our prior research on native vertebral osteomyelitis and postoperative spinal infection.Figure 1Network plot illustrating the co-occurrence of outcome criteria in prosthetic joint infection studies. Edge thickness reflects the frequency of the co-occurrence of each criterion. Each plot highlights one criterion, namely (1) clinical signs, (2) imaging, (3) microbiology, (4) histopathology, (5) antibiotics-related, (6) surgical-related, (7) mortality. Methods We conducted a comprehensive search of the Cochrane, Embase, Medline, and Scopus databases for studies published after 2005 that clearly defined outcomes for PJI. Eligible studies included randomized controlled trials and cohort studies with a minimum of 10 patients diagnosed with PJI. Our methodology adhered closely to the PRISMA guidelines. Using a saturation approach, we extracted and grouped explicit definitions of PJI outcomes into thematic criteria. A network plot (Figure 1) was used to visualize how frequently these criteria appeared and how they co-occurred across the included studies. Results Out of 7,584 screened studies, 552 (7.3%) met the inclusion criteria. This pilot analysis included 49 randomly selected studies (8,162 patients), mostly retrospective (48/49, 98%), focusing on mixed joint replacements (25/49, 51%), two-stage exchanges (15/49, 31%), or mixed surgeries (24/49, 49%). Only 6/49 (12.2%) applied a society-endorsed definition, and 13/49 (26.5%) cited a reference for their outcome definitions. Overall, 32/49 (65.3%) explicitly defined "success," 35/49 (71.4%) defined "failure," and 16/49 (32.7%) defined both. Most studies (25/49, 51%) had follow-up periods over two years, and 14/49 (28.6%) included patient-reported outcomes, identifying 14 unique PROMs (most commonly UCLA, HHS, and KSS scores). Functional outcomes were assessed in 13/49 (26.5%) studies. We identified 16 distinct outcome criteria across seven categories: clinical signs, microbiology, imaging, histopathology, antibiotics-related, surgical-related, and mortality. Network analysis revealed strong links among clinical signs, microbiology, surgical factors, mortality, and imaging. Conclusion Our pilot study found major variation in PJI outcome definitions, with few standardized criteria. A consensus-driven approach is needed to strengthen evidence synthesis and advance patient care in PJI. Disclosures All Authors: No reported disclosures

Aims Native vertebral osteomyelitis (NVO) and infective endocarditis (IE) are increasingly seen as interconnected conditions, sharing similar risk factors — such as advanced age and immunosuppression — and overlapping microbial profiles, notably Staphylococcus aureus and streptococci. When these infections occur together, they present distinct challenges in diagnosis and treatment, which can obscure clear outcomes and mortality estimates. Therefore, we aimed to systematically assess the combined mortality associated with concurrent NVO and IE and to detail the clinical characteristics of affected patients. Methods We conducted a systematic review following the PRISMA framework, searching MEDLINE, Embase, the Cochrane Library, and Scopus for relevant studies published between 1970 and October 2023. Studies included were those reporting mortality outcomes for at least ten adult patients with both NVO and IE. Two independent reviewers screened the literature, extracted data, and evaluated study quality using a modified Newcastle-Ottawa Scale. We then performed a random-effects meta-analysis to pool in-hospital, 1-month, 1-year, and 3-year mortality rates. Results A total of 16 studies (12 retrospective, 3 prospective, and 1 mixed design) involving 641 patients (mean age 67.1 years) with concomitant NVO and IE were included. The pooled in-hospital mortality rate was 10.0% (95% CI: 5.2–14.7%), with mortality rates of 5.6% (95% CI: 2.2–9.0%) at 1 month, 12.1% (95% CI: 5.3–18.8%) at 1 year, and 14.5% (95% CI: 4.3–24.8%) at 3 years. There was significant heterogeneity among studies (I² ranging from 46% to 86%). Common comorbidities included diabetes (24.6%), renal failure (17.3%), and immunosuppression (11.1%). The predominant pathogens identified were streptococci (31.3%), S. aureus (27.3%), and enterococci (13.7%). Approximately 40.6% of patients underwent surgical intervention, though its effect on mortality remains inconclusive. Overall, the certainty of the estimates was limited by imprecision and impossibility of perform subgroup analysis. Conclusion The coexistence of NVO and IE is associated with significant mortality, emphasizing the need for earlier diagnosis, coordinated multidisciplinary management, and standardized treatment protocols. Future prospective, high-quality studies are crucial to determine optimal diagnostic and surgical strategies for managing this complex clinical scenario.

Abstract Background and Aims Although the choice of dialysis technique is based on several factors, patient survival is undoubtedly one of the most relevant. In a context where randomization to either peritoneal dialysis (PD) or hemodialysis (HD) proved to be extremely challenging, previous meta-analyses were greatly limited due to the inclusion of historical studies. Method We performed a systematic review by searching multiple databases up to April 22nd, 2022. We included studies meeting the following criteria: adult patients (>18 years) with end-stage kidney disease on dialysis; comparison of PD versus HD; reporting mortality data via intention-to-treat analysis; initiation of dialysis after 2000; patient classification by dialysis modality at 90 days post-initiation; and ≥50 patients per group (Figs 1 and 2). The primary outcome was the association between dialysis modality (PD vs HD) and mortality assessed via hazard ratios (HR) [Fig. 3]. Subgroup analyses were conducted to explore potential sources of heterogeneity, including sex, age, diabetes, dialysis vintage, geographical location, HD access, and study cohort inclusion period [Figs 4 and 5]. Results Database search yielded 5317 citations, from which, 27 observational studies met the eligibility criteria, including 1 033 362 incident dialysis patients [Figs 1 and 2]. The pooled mortality HR for PD versus HD was 1.01 (95% CI 0.93–1.10 [Fig. 3]). Heterogeneity was substantial (I2 = 94%) and was largely explained by different baseline features of the included populations. A statistically significant subgroup effect was demonstrated for age (>65 vs.<65 years; P = 0.01), geographical location of the studies (Oceania vs. Europe vs. Asia vs. North America; P < 0.01), and HD vascular access (central venous catheter vs. arteriovenous fistula; P < 0.01, only one study included) [Figs 4 and 5]. Conclusion This meta-analysis suggests that overall PD and incentre HD likely carry equivalent survival benefits. However, differences were detected among subgroups based on age, geographic location, HD access type, but not on sex, diabetes status, dialysis vintage and study cohort inclusion period.

Abstract Background Although the choice of dialysis technique is based on several factors, patient survival is undoubtedly one of the most relevant. In a context where randomization to either peritoneal dialysis (PD) or hemodialysis (HD) proved to be extremely challenging, previous meta-analyses were greatly limited due to the inclusion of historical studies. Methods We performed a systematic review by searching multiple databases up to April 22nd, 2022. The primary outcome was the association between dialysis modality (PD vs HD) and mortality assessed via hazard ratios (HR). Subgroup analyses were conducted to explore potential sources of heterogeneity, including sex, age, diabetes, dialysis vintage, geographical location, HD access, and study cohort inclusion period. Results Database search yielded 5317 citations, from which, 27 observational studies met the eligibility criteria, including 1 033 362 incident dialysis patients. The pooled mortality HR for PD versus HD was 1.01 (95% CI 0.93–1.10). Heterogeneity was substantial ( I 2 = 94%) and was largely explained by different baseline features of the included populations. A statistically significant subgroup effect was demonstrated for age (> 65 vs.<65 years; p = 0.01), geographical location of the studies (Oceania vs. Europe vs. Asia vs. North America; p < 0.01), and HD vascular access (central venous catheter vs. arteriovenous fistula; p < 0.01, only one study included). Conclusions This meta-analysis suggests that overall PD and incentre HD likely carry equivalent survival benefits. However, differences were detected among subgroups based on age, geographic location, HD access type, but not on sex, diabetes status, dialysis vintage and study cohort inclusion period.

Abstract Background Studies aiming to synthetize data from literature are helpful to valid the robustness of associations, to assess the quality of the data, and, eventually, to propose recommendations. This is particularly evident for the huge amount of data reported for SARS-CoV-2. The aim of this study was to perform an umbrella review to identify the strength and validity of associations between variants of concern (VOCs) and pre-specified clinical outcomes in COVID-19 patients. Table 1 Effect size measures reported in the studies included in the review, divided by outcome. Acronyms: CI, confidence interval; OR: odds ratio; RR, risk ratio; cCFR, confirmed case-fatality risk; HFR, hospitalization-fatality risk; N/A, not available Methods An umbrella review according to the principles to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed searching multiple databases in January 2024. Peer reviewed systematic reviews considering ≥ 2 VOCs with a clinical outcome among death, hospitalization, severe disease, admission to intensive care unit (ICU), and mechanical ventilation were included. Data on study population and measures of association between clinical outcome and VOCs were considered. The quality of the studies was assessed through the AMSTAR-2 tool. The effect size measures with the confidence interval for each association between VOCs and clinical outcomes were reported. Subgroup analyses were performed, if possible. A citation matrix was used to assess the overlap between the systematic reviews included. Table 2 Risk of bias assessment of the included systematic reviews using the AMSTAR-2 score. In bold the key domains. Results A total of 11 studies were included in our review. 24 total comparison were considered, most regarding Omicron versus Delta (19/24), where Omicron was always associated with better clinical outcomes than Delta. The overall quality of the studies was low. None of the reviewed studies incorporated consideration of risk factors other than VOCs in evaluating clinical outcomes. The overlap between the included reviews is low, only 10% of them having a significant overlap ( &gt; 15%). Conclusion Our umbrella review shows the lower hazard on human health of the Omicron compared to Delta variant. However, the quality of the reviews included were generally low and there is a lack of correction with other risk factors such as comorbidities and vaccination status. While our review provides valuable insights into the association between VOCs and clinical outcomes of SARS-CoV-2 infection, further research incorporating risk factor analysis and ensuring methodological rigor is warranted. Disclosures All Authors: No reported disclosures

AbstractBackgroundCytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients (SOTRs). Secondary prophylaxis (SP) is not routinely recommended by guidelines on the management of CMV in SOTR but may be considered in certain higher‐risk situations.MethodsA comprehensive search of English language publications up to September 2023 was performed. The primary outcome was CMV relapse, defined as the recurrence of DNAemia or disease. Secondary outcomes included graft loss, mortality, and hematological toxicity. Meta‐analysis used the random‐effects model. The study protocol is registered in PROSPERO (no. CRD42022357028).ResultsSix retrospective comparative studies were included. A total of 520/727 (72%) of SOTR received SP with valganciclovir. The meta‐analysis did not demonstrate a significant difference in CMV relapse (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.79–2.63). Heterogeneity between the studies was low (I2 = 0%, p = 0.57). SP was significantly associated with a reduction in mortality (OR 0.2, 95% CI 0.07–0.54) but not graft loss (OR 0.67, 0.17–2.63). There was no significant difference in CMV relapse among kidney‐specific SOTR (OR 1.38, 95% CI 0.65–2.96).ConclusionEvidence from six nonrandomized studies is limited and cannot support a recommendation for or against routine SP in SOTR treated for CMV infection. Awaiting prospective‐controlled trials, the decision about SP should depend on individualized risk‐profile assessments by experienced clinicians. image

Infections of cardiac implantable electronic devices (CIEDs) and vascular grafts are some of the most dreaded complications of these otherwise life-saving devices. Many of these infections are not responsive to conventional treatment, such as systemic antibiotics and surgical irrigation and debridement. Therefore, innovative strategies to prevent and manage these conditions are warranted. Among these, there is an increasing interest in phages as a therapeutical option. In this review, we aim to collect the available evidence for the clinical application of phage therapy for CIED and vascular graft infections through literature research. We found 17 studies for a total of 34 patients. Most of the indications were left ventricular assist device (LVAD) (n = 20) and vascular graft infections (n = 7). The bacteria most often encountered were Staphylococcus aureus (n = 18) and Pseudomonas aeruginosa (n = 16). Clinical improvements were observed in 21/34 (61.8%) patients, with microbiological eradication in 18/21 (85.7%) of them. In eight cases, an adverse event related to phage therapy was reported. Phage therapy is a promising option for difficult-to-treat CIED and vascular graft infections by means of an individualized approach. Clinical trials and expanded access programs for compassionate use are needed to further unveil the role of phage therapy in clinical application.