Passerini, Matteo

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.

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.

Abstract Background Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. Methods We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). Results Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, −14%; 95% CI, −19% to −8%; P < .001; I 2 = 0%; relative risk, 0.58; 95% CI, .37–.92, P = .02, I 2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. Conclusions Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.