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Total joint arthroplasty is the recommended treatment for patients with end-stage osteoarthritis, as it reduces disability and pain and restores joint function. However, prosthetic joint infection is a serious complication of this procedure, with the two-stage exchange being the most common treatment method. While there is consensus on diagnosing prosthetic joint infection, there is a lack of agreement on the parameters that can guide the surgeon in performing definitive reimplantation in a two-stage procedure. One approach that has been suggested to improve the accuracy of microbiologic investigations before definitive reimplantation is to observe a holiday period from antibiotic therapy to improve the accuracy of cultures from periprosthetic tissues, but these cultures report some degree of aspecificity. Therefore, several pieces of evidence highlight that performing reimplantation using continuous antibiotic therapy should be considered a safe and effective approach, leading to higher cure rates and a shorter period of disability. Dosage of C-reactive protein (CRP), erythrocyte sedimentation rate (ERS) and D-dimer are helpful in diagnosing prosthetic joint infection, but only D-dimer has shown sufficient accuracy in predicting the risk of infection recurrence after a two-stage procedure. Synovial fluid analysis before reimplantation has been shown to be the most accurate in predicting recurrence, and new cutoff values for leukocyte count and neutrophil percentage have shown a useful predictive rule to identify patients at risk of unfavourable outcome. A new scoring system based on a numerical score calculated from the beta coefficient derived through multivariate analysis of D-dimer levels, synovial fluid leukocytes and relative neutrophils percentage has demonstrated high accuracy when it comes to guiding the second step of two-stage procedure. In conclusion, reimplantation may be a suitable option for patients who are on continuous therapy without local symptoms, and with CRP and ERS within the normal range, with low synovial fluid leukocytes (< 952/mL) and a low relative neutrophil percentage (< 52%) and D-dimer below 1100 µg/mL. A numerical score derived from analysing these three parameters can serve as a valuable tool in determining the feasibility of reimplantation in these patients.

Acquired Immunodeficiency Syndrome (AIDS) is a human viral infectious disease caused by the positive-sense single-stranded (ss) RNA Human Immunodeficiency Virus (HIV) (Retroviridae family, Ortervirales order). HIV-1 can be distinguished into various worldwide spread groups and subtypes. HIV-2 also causes human immunodeficiency, which develops slowly and tends to be less aggressive. HIV-2 only partially homologates to HIV-1 despite the similar derivation. Antiretroviral therapy (ART) is the treatment approved to control HIV infection, based on multiple antiretroviral drugs that belong to different classes: (i) NNRTIs, (ii) NRTIs, (iii) PIs, (iv) INSTIs, and (v) entry inhibitors. These drugs, acting on different stages of the HIV life cycle, decrease the patient’s total burden of HIV, maintain the function of the immune system, and prevent opportunistic infections. The appearance of several strains resistant to these drugs, however, represents a problem today that needs to be addressed as best as we can. New outbreaks of strains show a widespread geographic distribution and a highly variable mortality rate, even affecting treated patients significantly. Therefore, novel treatment approaches should be explored. The present review discusses updated information on HIV-1– and HIV-2–resistant strains, including details on different mutations responsible for drug resistance.

To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ARDS treated (N = 7) with the novel combination of ruxolitinib, a JAK1/2 inhibitor, 10 mg/twice daily for 14 days and eculizumab, an anti-C5a complement monoclonal antibody, 900 mg IV/weekly for a maximum of three weeks, or with the best available therapy (N = 10). Patients treated with the combination showed significant improvements in respiratory symptoms and radiographic pulmonary lesions and decrease in circulating D-dimer levels compared to the best available therapy group. Our results support the use of combined ruxolitinib and eculizumab for treatment of severe SARS-CoV-2-related ARDS by simultaneously turning off abnormal innate and adaptive immune responses.

The COVID-19 pandemic has reached direct and indirect medical and social consequences with a subset of patients who rapidly worsen and die from severe-critical manifestations. As a result, there is still an urgent need to identify prognostic biomarkers and effective therapeutic approaches. Severe-critical manifestations of COVID-19 are caused by a dysregulated immune response. Immune checkpoint molecules such as Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) play an important role in regulating the host immune response and several lines of evidence underly the role of PD-1 modulation in COVID-19. Here, by analyzing blood sample collection from both hospitalized COVID-19 patients and healthy donors, as well as levels of PD-L1 RNA expression in a variety of model systems of SARS-CoV-2, including in vitro tissue cultures, ex-vivo infections of primary epithelial cells and biological samples obtained from tissue biopsies and blood sample collection of COVID-19 and healthy individuals, we demonstrate that serum levels of PD-L1 have a prognostic role in COVID-19 patients and that PD-L1 dysregulation is associated to COVID-19 pathogenesis. Specifically, PD-L1 upregulation is induced by SARS-CoV-2 in infected epithelial cells and is dysregulated in several types of immune cells of COVID-19 patients including monocytes, neutrophils, gamma delta T cells and CD4+ T cells. These results have clinical significance since highlighted the potential role of PD-1/PD-L1 axis in COVID-19, suggest a prognostic role of PD-L1 and provide a further rationale to implement novel clinical studies in COVID-19 patients with PD-1/PD-L1 inhibitors.

BackgroundStroke has relevant morbidity and mortality despite appropriate treatments and early diagnosis. Beside common risk factors such as diabetes and atrial fibrillation, infections can be involved in stroke pathogenesis, probably causing a systemic release of cytokines and other inflammatory mediators, triggering a latent pro-thrombotic state or damaging the vascular endothelium. In other cases, infections can occur as stroke-like syndromes, requiring a high grade of suspicion to avoid a delay in establishing a correct diagnosis.ResultsTreatment of stroke or stroke-like syndromes of infectious origin can be difficult. When a previous infective event triggers stroke, Alteplase administration can be associated with a higher incidence of bleeding and the extension of the ischaemic area can be major than expected. On the other hand, when stroke is part of some infectious diseases’ presentation as in endocarditis, bacterial or tuberculous meningitis and meningo-vascular syphilis, a correct diagnosis can be difficult. The management of these stroke-like syndromes is not standardised because common treatments proven to be effective for patients with stroke of vascular origin can worsen the prognosis, as it can be demonstrated after to be incorrect Alteplase administration to patients with endocarditis with septic embolism to the brain is associated with an increase of the risk of haemorrhage.ConclusionsStroke or stroke-like syndrome of infectious origin can be observed in an important proportion of case presenting with sensory-motor deficit of unknown origin; their accurate diagnosis has a considerable impact in terms of treatment choices and outcome.

Antimicrobial resistance represents one of the main threats to healthy ecosystems. In recent years, among the multidrug-resistant microorganisms responsible for nosocomial infections, the Enterococcus species have received much attention. Indeed, Enterococcus have peculiar skills in their ability to acquire resistance genes and to cause severe diseases, such as endocarditis. This study showed the prevalence and antimicrobial resistance rate of Enterococcus spp. isolated from clinical samples, from January 2015 to December 2019 at the University Hospital “San Giovanni di Dio e Ruggi d’Aragona” in Salerno, Italy. A total of 3236 isolates of Enterococcus faecalis (82.2%) and Enterococcus faecium (17.8%) were collected from urine cultures, blood cultures, catheters, respiratory tract, and other samples. Bacterial identification and antibiotic susceptibility were performed with VITEK 2. E. faecium showed a high resistance rate against ampicillin (84.5%), ampicillin/sulbactam (82.7%), and imipenem (86.7%), while E. faecalis showed the highest resistance rate against gentamicin and streptomycin high level, but both were highly sensitive to such antibiotics as tigecycline and vancomycin. Studies of surveillance are an important tool to detect changes in the resistance profiles of the main pathogens. These antimicrobial susceptibility patterns are necessary to improve the empirical treatment guideline of infections.

Abstract Guillain-Barrè syndrome (GBS) is an acute immune-mediated neuropathy, possibly triggered by a recent infection or vaccination, and driven by an immune attack targeting the peripheral nervous system. GBS typically leads to ascending limb weakness, often with sensory and cranial nerve involvement 1–2 weeks after immune stimulation, but emergency and neurology physicians should be aware of its important clinical heterogeneity. In rare cases, bilateral facial nerve palsy can be the main clinical manifestation, as the case of the variant formerly known as bilateral facial weakness with paresthesias. An increasing number of case reports of GBS in patients receiving COVID-19 vaccination have been reported both during the pre-clinical phase and after large-scale authorities’ approval. We report two cases of bifacial palsy with paresthesias, a rare variant of GBS, both occurring after the first dose of COVID-19 vaccine Vaxzevria™ (formerly COVID-19 vaccine AstraZeneca), showing a favorable outcome after high-dose immunoglobulin therapy, and discuss the literature of GBS post-COVID-19 vaccination.

Fracture-related infections (FRIs) represent a significant complication in orthopedic trauma care, often leading to delayed bone healing, prolonged hospital stays, and increased patient morbidity. Pathogenesis involves microbial contamination during injury or surgery, compounded by patient-related risk factors such as diabetes, smoking, or immunosuppression. Diagnosis of FRI relies on a combination of clinical, radiological, and microbiological criteria. Common signs include persistent pain, swelling, erythema, purulent discharge, and non-union of the fracture. FRIs are classified based on the timing of infection onset into acute, delayed, and chronic forms, each requiring tailored management strategies. Treatment generally involves aggressive surgical debridement, possible hardware removal or retention, and targeted antibiotic therapy. In cases of severe tissue loss, reconstructive procedures may be necessary to restore bone and soft tissue integrity. Treatment strategies include early administration of prophylactic antibiotics, meticulous surgical technique, and timely soft tissue coverage in open fractures. A multidisciplinary approach involving orthopedic surgeons, infectious disease specialists, and microbiologists is essential for successful management. Early recognition and appropriate intervention are crucial to improving outcomes and minimizing long-term disability in patients with fracture-related infections.

Drug repurposing is sparking considerable interest due to reduced costs and development times. The current study details the screening of teniposide, an antitumor drug, for its antibacterial activity against both Gram‐positive and Gram‐negative strains, with a focus on Staphylococcus epidermidis ( S. epidermidis ), the primary causative agent of nosocomial and transplant‐related infections. The cytotoxicity was evaluated through 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and hemolysis assays on immortalized human keratinocyte (HaCaT) cells and human erythrocytes. After 20 h of treatment, the recorded concentrations causing 50% cytotoxicity (CC 50 ) and hemolysis (HC 50 ) were 33.63 and 121.55  μ g/mL, respectively. The antibacterial screening employed disk diffusion, the broth microdilution method, LIVE/DEAD staining, and a time‐killing test. The drug induced a growth inhibitory area in the 22–25 mm range for all Gram‐positive strains. The minimum concentration that inhibited 90% of bacteria (MIC 90 ) was 6.25  μ g/mL against Staphylococcus aureus and S. epidermidis and 12.5  μ g/mL versus Enterococcus faecalis , exhibiting bactericidal action. Treatment resulted in S. epidermidis cell morphology deformities and damage to the cell membrane, observed by scanning electron microscopy (SEM). Mechanism analysis revealed alterations in the selective permeability of the cell membrane, observed under the fluorescence microscope by the absorption of propidium iodide (PI). The synergistic effect of teniposide in combination with fosfomycin and gentamicin was documented by disk diffusion and checkboard assay, recording a fractional inhibitory concentration index (FICI) of 0.28 and 0.37, respectively. The drug’s action on S. epidermidis biofilm biomass was investigated using crystal violet (CV) and MTT. Teniposide affected biofilm viability in a dose‐dependent manner, inducing, at a concentration of 3.12  μ g/mL, a matrix inhibition of about 42% and 61%, with a sessile metabolic activity of 54% and 24% recorded after 2 and 24 h, respectively. Overall, this study suggests the potential repurposing of the anticancer drug teniposide as a therapeutic agent to counteract S. epidermidis infections.

Infections caused by antibiotic-resistant bacteria represent a serious threat to global public health. Recently, due to its increased resistance to carbapenems and β-lactams, Klebsiella pneumoniae has become one of the main causes of septicemia, pneumonia, and urinary tract infections. It is crucial to take immediate action and implement effective measures to prevent further spread of this issue. This study aims to report the prevalence and antibiotic resistance rates of K. pneumoniae strains isolated from clinical specimens from 2015 to 2020 at the University Hospital of Salerno, Italy. More than 3,800 isolates were collected from urine cultures, blood cultures, respiratory samples, and others. K. pneumoniae isolates showed broad resistance to penicillin and cephalosporins, and increased susceptibility to fosfomycin and gentamicin. Extended spectrum beta-lactamase (ESBL) isolates accounted for 20–22%. A high percentage of strains tested were resistant to carbapenems, with an average of 40% to meropenem and 44% to ertapenem. The production of ESBLs and resistance to carbapenems is one of the major public health problems. Constant monitoring of drug-resistant isolates is crucial for developing practical approaches in implementing antimicrobial therapy and reducing the spread of K. pneumoniae in nosocomial environments.