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Introduction The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data. Methods Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support. Results Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70–84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37–0.66, P Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46–10.91, P Conclusions Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed.

To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19).Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort.Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93-6.03), a oxygen saturation to fraction of inspired oxygen (SpOThe FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion.

Mycobacterium marinum (M. marinum) is a free-living, slow grower nontuberculous mycobacteria (NTM), strictly related to Mycobacterium tuberculosis, that causes disease in fresh and saltwater fish and it is one of the causes of extra-pulmonary mycobacterial infections, ranging in human from simple cutaneous lesions to disseminated forms in immunocompromised hosts. The first human cases of M. marinum infection were reported from skin lesions of swimmers in a contaminated pool, in 1951, in Sweden by Norden and Linell. Two conditions are required to develop M. marinum infection: (1) skin solution of continuity and (2) exposure to the contaminated water or direct contact with fish or shellfish. The so-called "fish-tank granuloma", the most frequent cutaneous manifestation of M. marinum infection, is characterized by a single papulonodular, verrucose and/or ulcerated granulomatous lesion in the inoculum site. Careful patient's history collection, high clinical suspicion and appropriate sample (e.g. cutaneous biopsy) for microbiological culture are crucial for a timely diagnosis. The treatment is not standardized yet and relies on administration of two active antimycobacterial agents, always guided by antimicrobial susceptibility test on culture, with macrolides and rifampin as pivotal drugs, as well as prompt surgery when feasible. In this narrative review, we provide to Clinicians an updated report of epidemiology, microbiological characteristics, clinical presentation, diagnosis, and management of M. marinum infection.

Patients with specific hematological malignancies (HM) are at increased risk for severe disease and death from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy subjects, vaccination against SARS-CoV-2 has been demonstrated to be highly effective in disease prevention; however, immunocompromised patients were largely excluded from vaccine randomized controlled trials. In this review, we overview available non-randomized studies addressing effectiveness and safety of several coronavirus disease 2019 (COVID-19) vaccines in patients with HM. Overall, COVID-19 vaccines are safe in patients with HM, with adverse events similar to those in the general population. Though serology testing is not recommended as a test to evaluate vaccine effectiveness, a correlation between higher antibody levels and protection against infection has been reported. Studies evaluating humoral response to COVID-19 vaccine in HM patients demonstrate low immunogenicity, mainly in patients with lymphoproliferative disorders, as well as with certain drugs, including mainly anti-CD20 antibodies, Bruton tyrosine kinase inhibitors, and also ruxolitinib and venetoclax. Seropositivity rates of patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia following mRNA vaccination reach 40%–50%. T-cell responses to vaccination are also impaired among these patients. Better humoral response rates are reported in multiple myeloma patients and hematopoietic stem-cell transplant, reaching ∼75%–80%, but not in patients following chimeric antigen receptor T-cell therapy. Patients with chronic myeloid leukemia and myeloproliferative diseases have high response rate to vaccination. Third mRNA vaccine dose is currently recommended to all HM patients. Alternative approaches for vaccination and prevention in patients unable to mount an immune response following full vaccination are provided in the review.

Different antivirals are available for the treatment of outpatients with COVID-19. Our aim was to describe a real-world experience of outpatient management of COVID-19 subjects at high risk of progression.This prospective observational study conducted in the University Hospital of Pisa (January 2022-July 2022) included consecutive COVID-19 outpatients with at least one risk factor for disease progression. Patients received nirmatrelvir/ritonavir, molnupiravir, or 3-day remdesivir, according to the Italian Medicines Agency (AIFA) indications. All patients were followed up until 30 days from the first positive nasopharyngeal swab. The primary endpoint was a composite of death or hospitalization. Secondary endpoints were occurrence of adverse events and a negative test within 10 days from the first positive test. Multivariable analysis was performed to identify factors associated with death or hospitalization.Overall, 562 outpatients were included: 114 (20.3%) received molnupiravir, 252 (44.8%) nirmatrelvir/ritonavir, and 196 (34.9%) 3-day remdesivir. The composite endpoint occurred in 2.5% of patients and was more frequent in patients treated with remdesivir (5.1%) compared with molnupiravir (1.8%) or nirmatrelvir/ritonavir (0.8%, ANOVA among groups p = 0.012). On multivariable Cox regression analysis, presence of ≥ 3 comorbidities, hematological disease, gastrointestinal symptoms, and each-day increment from symptoms onset were factors associated with death or hospitalization, while antiviral treatment was not a predictor. Adverse events occurred more frequently in the nirmatrelvir/ritonavir group (49.2%). Nirmatrelvir/ritonavir compared with remdesivir was associated with a higher probability of having a negative test within 10 days from the first positive one.Death or hospitalization did not differ among high-risk COVID-19 outpatients treated with currently available antivirals. Safety and time to a negative test differed among the three drugs.

BACKGROUND: SARS-CoV-2 pandemic affected tuberculosis (TB) management. This Italian nationwide survey assessed COVID-19 impact on TB care and outcomes. MATERIALS AND METHODS: Twenty-one hospitals or referral centres fulfilled an online survey. Primary objective was to describe clinical features, outcomes and retention in care in subjects with latent TB infection (LTBI) or disease over the first wave of COVID-19 pandemic. Secondary objectives were the assessment of risk factors, co-morbidities, diagnostics, radiological findings, and outcomes of COVID-19 in the study population. RESULTS: 254 patients with LTBI or active TB were included. In co-infected (SARS-CoV-2, LTBI/TB) patients, recovery occurred in 29/32 (90.6%) cases, death in one case. High retention in care was preserved. CONCLUSION: in our cohort, outcomes did not seem to be adversely conditioned by incident COVID-19.

BACKGROUND: Treatment outcomes in multidrug‐resistant TB (MDR‐TB) patients are suboptimal in several low‐incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18‐year period. Secondary outcomes were treatment outcomes in certain drug‐containing regimens and the possibility for the WHO shorter MDR‐TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug‐resistance patterns were found: MDR‐TB in 68.6%, pre‐extensively drug‐resistant TB (pre‐XDR‐TB) in 30.4% and XDR‐TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR‐ (68.8%) and pre‐XDR‐TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR‐TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR‐ and pre‐XDR‐TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.

Introduction Daptomycin is a bactericidal lipopeptide antibiotic approved for the treatment of systemic infections (i.e. skin and soft tissue infections, bloodstream infections, infective endocarditis) caused by Gram-positive cocci. It is often prescribed in association with a partner drug to increase its bactericidal effect and to prevent the emergence of resistant strains during treatment; however, its synergistic properties are still under evaluation. Methods We performed a systematic review to offer clinicians an updated overview of daptomycin synergistic properties from in vitro and in vivo studies. Moreover, we reported all in vitro and in vivo data evaluating daptomycin in combination with other antibiotic agents, subdivided by antibiotic classes, and a summary graph presenting the most favourable combinations at a glance. Results A total of 92 studies and 1087 isolates (723 Staphylococcus aureus, 68 Staphylococcus epidermidis, 179 Enterococcus faecium, 105 Enterococcus faecalis, 12 Enterococcus durans) were included. Synergism accounted for 30.9% of total interactions, while indifferent effect was the most frequently observed interaction (41.9%). Antagonistic effect accounted for 0.7% of total interactions. The highest synergistic rates against S. aureus were observed with daptomycin in combination with fosfomycin (55.6%). For S. epidermidis and Enterococcus spp., the most effective combinations were daptomycin plus ceftobiprole (50%) and daptomycin plus fosfomycin (63.6%) or rifampicin (62.8%), respectively. Future perspectives We believe this systematic review could be useful for the future updates of guidelines on systemic infections where daptomycin plays a key role.

Endoscopic endonasal skull base surgery (EESBS) is a clean-contaminated procedure. Guidelines regarding the antibiotic prophylaxis in EESBS have not been developed yet, and today, there are no universally accepted protocols. In this article, we investigated the efficacy of our new ultra-short antibiotic prophylaxis protocol for EESBS guided by the cultural results of preoperative microbiological nasal swabs. We defined as “nasal swab-related antibiotic protocol” the administration of a first-generation cephalosporin (cefazolin 2 g) in patients whose nasal swabs revealed the presence of normal nasal flora or methicillin-sensitive Staphylococcus aureus (MSSA), and the administration of vancomycin 1 g intravenously in patients whose nasal swabs revealed the presence of methicillin-resistant Staphylococcus aureus (MRSA) or with reported cephalosporin/penicillin allergy. This case-control study included 120 patients who underwent EESBS. The case group included 60 cases who received the “nasal swab-related antibiotic protocol,” while the control group included 60 cases who received the “standard hospital antibiotic protocol” used in neurosurgery (cefazolin 2 g plus metronidazole 500 mg at induction, and 2 g of cefazolin repeated after 180 min). The preoperative microbiological nasal swabs showed normal nasal flora in 42 patients (70%), MSSA in 17 patients (28.3%), and MRSA in 1 patient (1.6%). During the study period, no cases of meningitis or sinusitis occurred in the case group (“nasal swab-related antibiotic protocol”), while two infections (3.3%, 1 sinusitis and 1 meningitis) were reported in the control group (“standard hospital antibiotic protocol”). Mean length of hospitalization was 6.5 days for the case group and 8.5 days in the control group. “Standard hospital antibiotic protocol” is less expensive (range, 2.88–5.42 euros) compared with our new “nasal swab-related antibiotic protocol” (range, 10.02–32.56 euros), but in line with other antibiotic prophylaxis protocols reported in literature. The low complication rates of our case series (0%) is comparable to complication rates reported in literature (1.6% for meningitis and 8% for sinusitis). Compared with other perioperative antibiotic regimens reported in literature, the “nasal swab-related antibiotic protocol” is cheap and at least equally effective. We discuss the rationale on which we based the choice of chemoprophylaxis, the timing, and the length of our regimen. Our study confirmed the safety and efficacy of our easily applicable and low-cost antibiotic prophylaxis protocol.

The emerge of drug-resistant tuberculosis (TB) strain in recent decades is hampering the efforts of the international community to eliminate the disease worldwide. The World Health Organization (WHO) has drafted many strategies to achieve this ambitious goal. In the very beginning, the aim was to standardize inadequate regimens used in many countries and, thereafter, evolved to tackle the social determinants which hinder TB elimination. However, following the path of narrowing the clinical vision to deal with TB, there is an increased need to personalize the treatment considering both patients and pathogen unique characteristics. In our narrative review, we report the advantages and the backwards in developing a method to implement the concept of precision medicine to the treatment of TB. In this dissertation, we highlight the importance to address different aspects of the diseases encompassing the host and pathogen features, as well as the needs to further implement an adequate follow-up based on the available resources. Nevertheless, many things may hamper the vision of precision medicine in TB, such as the complexity and the costs to develop novel compounds and the costs related to global-scale implementation of patient-centered follow-up. To achieve the ambitious goal of TB elimination, a radical change in TB treatment is needed in order to give a more comprehensive approach based both on patients' peculiarities and driven by drug susceptibility tests and whole-genome sequencing.

Background Since 2014, the migrant population residing in Europe has dramatically increased. Migrants’ unmet health needs represent a barrier to integration and should be promptly addressed, without stigma, in order to favour resettlement. Methods All-cause of admissions in the migrant population at the Infectious Disease Clinic of Policlinico San Martino Hospital in Genoa between 2015 and 2017 were analysed. Patients were classified by duration of residence in Italy according to the Recommendation on Statistics of International Migration, cause of hospitalization, and region of origin. All data were evaluated with SPSS Statistics. Results Two hundred thirty-five people were admitted, 86 (36.5%) of them residing in Italy for less than 1 year. Except for a significant increase in migrants from Africa, there was no change considering the area of origin, hospitalization reason or by comparing residency in Italy for more or less than 1 year. A considerable number of hospitalizations were related to non-communicable pathologies and latent tuberculosis infection. Residents in Italy for less than 1 year or with active tuberculosis had prolonged hospitalizations, while HIV-infected had shorter hospital stays. Conclusions No difference in terms of diagnosis were found between migrants with longer or shorter period of residence in Italy. Adequate outpatient services for the management of communicable diseases could significantly reduce the length of hospitalizations in the migrant population.

Summary Objective HIV-infection increases the risk to progress to active-tuberculosis (TB). Detection of latent TB infection (LTBI) is needed to eventually propose preventive-therapy and reduce TB reservoir. QuantiFERON-TB Plus (QFT-Plus)-test identifies LTBI. Currently, only two studies on QFT-Plus accuracy in HIV-infected-population are available in high TB-endemic-countries. Therefore we aimed to evaluate the effect of HIV-infection on QFT-Plus accuracy to detect LTBI in a low TB-endemic-country. Methods We enrolled 465 participants, among the 167 HIV-infected-persons: 32 with active-TB (HIV-TB), 45 remote-LTBI (HIV-LTBI) and 90 at low M. tuberculosis (Mtb)-infection risk. Among the 298 HIV-uninfected-persons: 170 with active-TB, 76 recent-LTBI, 34 remote-LTBI and 18 with low Mtb-infection risk. Results QFT-Plus sensitivity was similar in TB regardless of HIV-status. CD4-count did not influence the distribution of IFN-γ values in HIV-TB and HIV-LTBI. Moreover HIV-LTBI and HIV-uninfected remote LTBI had a similar proportion of results in the uncertain range (IFNγ ≥0.2 ≤ 0.7 IU/ml) differently from those LTBI-persons reporting recent-exposure (p = 0.016). Cytometry results demonstrated that CD8-response was similar in HIV-infected- and -uninfected-persons whereas CD4-response was impaired in HIV-infected-persons (p = 0.011). Conclusions HIV-infection does not affect QFT-Plus response in active-TB, whereas the time of exposure influences the proportion of uncertain-results in LTBI.

Mould infections may follow traumatic injuries, with direct fungal inoculum in the site of injury and subsequent angioinvasion, possibly resulting in tissue necrosis and systemic dissemination. The pathogenesis of mould infections following trauma injuries presents unique features compared with classical mould infections occurring in neutropenic or diabetic patients, because a large fraction of post-traumatic mould infections is observed in previously healthy individuals. Most of the published clinical experience and research on mould infections following traumatic injuries regards soldiers and infections after natural disasters. However, following trauma and soil contamination (e.g., agricultural or automotive injuries) other immunocompetent individuals may develop mould infections. In these cases, delays in correct diagnosis and treatment may occur if pertinent signs such as necrosis and absent or reduced response to antibacterial therapy are not promptly recognized. Awareness of mould infections in at-risk populations is needed to rapidly start adequate laboratory workflow and early antifungal therapy in rapidly evolving cases to improve treatment success and reduce mortality.

Purpose To investigate the effects of different antibiotic prophylaxis regimens in patients with diabetes mellitus (DM) candidates to trans-rectal ultrasound-guided prostate biopsy (TRUSPB). Methods 143 outpatients with DM who underwent TRUSPB during the period 2018–2020 were selected from a cohort of 1150 patients in 3 different institutions. Exclusion criteria were allergies, concomitant anti-platelet therapies and uncontrolled DM. Different antibiotic prophylaxis regimens were adopted. Bacterial resistance levels to fluoroquinolones into the different communities were also collected. Univariable and multivariable binomial logistic regression analyses were used to assess the odds ratio (OR) with 95% confidence intervals (CIs) testing the risk of infective complications' occurrence after adjusting for clinical covariates. Results Overall, DM patients were significantly associated with infective complications' occurrence (p 37 °C were found in 9.1% and 1.5% (p Conclusion Fluoroquinolones were active in antibiotic prophylaxis of diabetic patients who had undergone to TRUSPB independently from the level of bacterial resistance found in the community. These results conflict with the recent European warning and support the Japanese and American guidelines on the topic.

Strains of drug-resistant nontyphoidal

Among central nervous system (CNS) infections (e.g., meningitis, brain abscess, ventriculitis, transverse myelitis), those caused by

Genitourinary tuberculosis (GUTB) represents a disease often underestimated by urological specialists, particularly in settings such as the European one, where the pathology is less frequent. Similar to other uncommon diseases at these latitudes, GUTB is a neglected clinical problem. In this light, the aim of this review is to give a comprehensive overview of GUTB in order to provide a useful tool for urologists who seldomly manage this disease. A non-systematic review of genitourinary tuberculosis was performed on relevant articles published from January 1990 to July 2021 using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. GUTB represents up to a quarter of extrapulmonary tuberculosis (EPTB) cases. Diagnostic, therapeutic and surgical work-up have been deeply reviewed and summarized. The mass migration of refugees to Europe as well as the ease of international travel is gradually leading to an upsurge in urological diseases such as GUTB, which were previously only rarely encountered in some European countries. The poor TB knowledge of European urologists should be improved through medical education courses, webinars or telematic means.

The recent rise in migration from Africa through the Mediterranean basin into Europe has resulted in an increased incidence of uncommon diseases such as schistosomiasis and genito-urinary tuberculosis, which were previously largely unknown in this region. This study aimed to evaluate the insight of European urologists into diagnosing and managing these disease conditions and to determine whether they were adequately prepared to deal with the changing disease spectrum in their countries. A survey including specific questions about the diagnosis and management of ‘tropical’ urological diseases was distributed among urologists working in Europe and Africa. Multivariate logistic regression models were performed to detect the continent (African or European) effect on knowledge of and insight into tropical urological diseases. A total of 312 surveys were administered. African and European respondents accounted for 109 (36.09%) and 193 (63.91%) respondents, respectively. The multivariate logistic regression analysis demonstrated a significant deficiency in the knowledge of tropical urological diseases in the European cohort compared with the African cohort (p

Objective: To describe a left epididymitis and para-aortical involvement caused by Mycobacterium tuberculosis hominis reactivation after bacillus Calmette-Guérin instillation for non-muscle-invasive bladder cancer. Patient and methods: A Caucasian male, aged 76 years, exposed to bacillus Calmette-Guérin for a high-grade non-muscle-invasive bladder cancer in 2015, reported painful and progressive left scrotal swelling with purulent discharge from a cutaneous fistulous track that yielded, on liquid culture, a pan-susceptible Mycobacterium tuberculosis hominis strain. Moreover, after 6 months of anti-tuberculosis treatment, an abdominal peri-aortic mass, sized 4 cm, was found and a surgical biopsy showed necrotizing granulomas; however, although smear microscopy and Xpert MTB/Rif™ performed on fresh biopsy sample were positive, liquid cultures resulted negative, indicating treatment efficacy. Results: Numerous peculiar and multi-organ involvement due to BCGitis after intravesical immunotherapy have been previously described, including 17 scientific articles about epididymitis, however, no reports so far showed reactivation of Mycobacterium tuberculosis hominis after bacillus Calmette-Guérin treatment. Conclusion: Although BCGitis is more prevalent in patients undergoing bacillus Calmette-Guérin instillation for non-muscle-invasive bladder cancer, tuberculosis by other species of Mycobacterium tuberculosis should be always ruled out by molecular and conventional microbiology in patients with a history of Mycobacterium tuberculosis hominis exposure.

Background: Tuberculosis (TB) unevenly affects individuals across the globe, especially in rural areas of low-income countries. Aim of the study was to assess the impact of social protection to increase TB awareness on treatment outcomes among TB patients in a rural area of Senegal. Materials & methods: The study, conducted in Fimela district (Senegal) from 1 January 2010 to 31 December 2019 and the intervention started from 31 January 2013, includes activities to increase awareness, active case finding, active follow-up and social protection. Results: Overall, 435 subjects – mainly male and young – were included in the analysis. Among TB cases, 94% had pulmonary involvement, 87% had no previous TB history, and 6% resulted positive HIV. Improved outcome was observed once intervention began (from 71 to 91%, p

Rabies is a vaccine preventable zoonotic disease with a significant mortality burden worldwide. Several years of vaccination campaigns in wildlife animals have now achieved the control of rabies in Western Europe through a vaccination belt in front of endemic Eastern European countries. Nevertheless, rabies could be imported both by travellers from areas without an active public control of the disease or by animals coming from areas where the virus circulates in wildlife fauna. The knowledge of the current world epidemiology combined with a high index of clinical suspicion are needed to reach a diagnosis of rabies, especially in case of atypical presentation or without a history of animal exposure. The pre-travel counselling to people visiting highly endemic areas is essential to give information on how to reduce exposure to potential sources of infection and to select those subjects who could benefit from pre-travel vaccination. Rabies is almost invariably fatal, but the prompt administration of a vaccine course combined with anti-rabies immunoglobulins significantly reduces the probability to develop life-threatening consequences. In this review, we give a brief epidemiological and clinical update about rabies in Europe.