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Background: The 2023 European Society of Cardiology (ESC) guidelines for the management of infective endocarditis (IE) highlighted the essential role of multimodal imaging in the diagnostic algorithm of IE and its complications. Methods: We hereby report a case series of IE in which the diagnosis was confirmed or excluded by the use of multimodal imaging during the period between January 2024 and July 2024 at the Infectious Diseases Clinic, Perugia Hospital, Italy. Results: Six patients were retrospectively included. Prosthetic valve endocarditis (PVE) was suspected in four patients and native valve endocarditis (NVE) in two cases. In patients with prosthetic valves, 18F FDG-PET/CT was performed, except in one case (P1) where cardiac CTA was performed for suspicion of perigraft aneurysm. Patients underwent transesophageal echocardiography (TOE), which was diagnostic in two cases and inconclusive in the remaining cases. In case of inconclusive TOE, the use of multimodal imaging added a major criterion and allowed us to consider (from ‘rejected’ to ‘possible’) or confirm (from ‘possible’ to ‘definite’) the diagnosis of EI based on the 2023 Duke–ESC Criteria. In one case (P6), it was possible to exclude the diagnosis. For patients with diagnostic TOE, 18F FDG-PET/CT allowed for the enhancement of diagnostic accuracy, identifying the site of valve involvement and the extension of the infection to the device (cases P3 and P5, respectively). Conclusions: In clinical practice, the use of cardiac CTA and/or 18F FDG-PET/CT based on the latest ESC guidelines demonstrated a significant impact on the diagnosis and therapeutic management of IE.

Background. Pseudomonas aeruginosa is one of the major concerns among bacterial diseases even when it shows a wild-type susceptibility pattern. In 2020, EUCAST reconsidered antibiogram interpretation shifting “I” from “intermediate” to “sensible, increased exposure” with possible significant impact on antibiotic prescription. The aim of this study was to evaluate mortality in patients with P. aeruginosa bloodstream infections treated with antipseudomonal penicillins or cephalosporins vs. carbapenems and ceftazidime/avibactam. Methods. This is a retrospective observational study. All the patients with a bloodstream infection due to P. aeruginosa admitted to our hospital were enrolled. Exclusion criteria were as follows: extremely critical conditions, age p > 0.1). In group A, in-hospital BSI-related mortality was 23.2% (13/56), while it was 14.3% (3/21) in group B (p > 0.1). After multivariate analysis, only the PITT score represented a risk factor for BSI-related mortality (OR 2.917, 95% CI 1.381–6.163). Conclusions. Both all-cause and BSI-related mortality were comparable between the two groups. Treatment with carbapenem or ceftazidime/avibactam did not represent a protective factor for mortality in wild-type P. aeruginosa BSI.

Abstract Introduction Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Background and Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. Results: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. Conclusions: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Background. Urinary tract infections (UTIs) and asymptomatic bacteriurias (ABU) represent a large field of interest for antimicrobial stewardship programmes especially after 2020 EUCAST update in antimicrobial susceptibility testing interpretation and the possible related increase in carbapenems’ prescription rate. The aim of this study was to evaluate the impact of the 2020 EUCAST update on antibiotic prescription in UTI due to Pseudomonas aeruginosa organism and their characteristics. Methods. A retrospective observational study. We enrolled all the patients with P. aeruginosa isolation from urine, admitted to our hospital from 2018 to 2021. We compared demographic, clinical, and microbiological characteristics and treatment between cases before 2020 EUCAST update (period A, 2018–2019) and after it (period B, 2020–2021). Results. A total of 643 cases was analysed, 278 in period A and 365 in period B; 65% were ABU. Carbapenems’ prescription rate significantly increased in period B when considering ABU alone (21.4% vs. 41%, p = 0.016) and all the treated cases (treated ABU and UTI; 27.8% vs. 41.4%, p = 0.013); anti-Pseudomonas cephalosporins prescription significantly decreased in period B when considering ABU alone (15.7% vs. 3.6%, p = 0.021), UTI alone (20.7% vs. 5.9%, p = 0.009) and all the treated cases (18.5% vs. 5.9%, p = 0.001). Conclusions. The 2020 EUCAST update could have contributed to an increase in carbapenem prescriptions. UTI and ABU represent a large field of interest for stewardship interventions both from a diagnostic and therapeutic point of view.

Objectives: Heavily treatment-experienced (HTE) people living with HIV (PLWH) pose unique challenges due to limited antiretroviral treatment (ART) options. Our study aimed to investigate the prevalence and features of HTE individuals followed up in the Italian Cohort Naïve Antiretrovirals (ICONA) cohort as of December 31, 2021. Methods: HTE were defined based on meeting specific conditions concerning their current ART and their ART history up to December 31, 2021. Descriptive statistics were performed by HTE status. Regression analyses explored factors associated with becoming HTE based on pre-ART patients' characteristics. Cluster dendrogram analysis provided insights into subgroups with inadequate responses based on clusters of differentiation (CD4) counts and viral load (VL) trajectories. Results: Among the 8758 PLWH actively followed in our cohort, 163 individuals (1.9%), mainly female, younger, Italian, and infected through heterosexual contact, met the HTE criteria. A lower CD4 count at ART initiation (odds ratio [OR] 1.60 per 100 cells/mmc lower CD4, 95% confidence interval [CI] 1.06-2.41, P = 0.03) and hepatitis C virus antibody positivity (OR 1.90, 95% CI 1.16-3.11, P = 0.01) were associated with higher HTE risk. Thirty PLWH exhibited ongoing immune-virological failure (18% of the HTE subgroup and 0.003% of the total population). Thirty PLWH exhibited ongoing immune-virological failure (i.e., with a current CD4 count 200 copies/mL). A cluster analysis identified 13 (43%) with a current CD4 count

Background: Bictegravir (BIC), a recently introduced integrase inhibitor, is available in a single tablet regimen with tenofovir alafenamide (TAF) and emtricitabine (FTC) (BIC-STR). This study aimed to describe a real-life experience with BIC-STR. Methods: We retrospectively analyzed the data of people living with HIV (PLWH) on antiretroviral therapy (ART) with BIC-STR followed by the Clinic of Infectious Diseases of Perugia (Perugia, Italy) from September 2019 to February 2023. Results: 270 PLWH were enrolled with a median follow-up time on BIC-STR of 2.2 years (IQR 1.2–2.7). In the overall population, in treatment-experienced (N = 242), in treatment-naïve (N = 28), and in population with age > 60 years old (N = 86), we observed that CD4 cell count improved in absolute number, percentage and CD4/CD8 ratio, under BIC-STR. Patients with viremia < 50 cp/mL increased in all groups. In the overall population, previous ART with TAF and nadir CD4 cell count favored immunological recovery. In the ART-experienced group, time in therapy with BIC-STR was associated with HIV-RNA undetectability. In the older group, previous opportunistic infection and advanced age were associated with lower CD4 count. Conclusions: BIC-STR was demonstrated, in real-life, to be a valid option for a switch, such as initial ART.

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.

Aspergillus fumigatus is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor A. fumigatus colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and A. fumigatus conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication. As a consequence, 3-IAld limited the pathogenic sequelae of fungal superinfection as revealed by the controlled fungal burden and restrained inflammatory pathology. These results point to indole compounds as potential agents to prevent CAPA.

Non-structural protein 5 (Nsp5) is a cysteine protease that plays a key role in SARS-CoV-2 replication, suppressing host protein synthesis and promoting immune evasion. The investigation of natural products as a potential strategy for Nsp5 inhibition is gaining attention as a means of developing antiviral agents. In this work, we have investigated the physicochemical properties and structure-activity relationships of ellagic acid and its gut metabolites, urolithins A–D, as ligands of Nsp5. Results allow us to identify urolithin D as promising ligand of Nsp5, with a dissociation constant in the nanomolar range of potency. Although urolithin D is able to bind to the catalytic cleft of Nsp5, the appraisal of its viral replication inhibition against SARS-CoV-2 in Vero E6 assay highlights a lack of activity. While these results are discussed in the framework of the available literature reporting conflicting data on polyphenol antiviral activity, they provide new clues for natural products as potential viral protease inhibitors.

Background: this study aims to evaluate the efficacy of tixagevimab/cilgavimab (Evusheld™) against various SARS-CoV-2 variants, including newer Omicron sublineages, in an immunocompromised cohort and in vitro. Study design: Conducted in Italy, this research involves immunocompromised patients who received Evusheld. It evaluates serum neutralization activity against different SARS-CoV-2 strains (20A.EU1, BA.5, BQ.1, XBB.1.5, XBB.1.16, and EG.5) before (T0), after 14 (T1), and after 30 (T2) days from the tixagevimab/cilgavimab injection. Furthermore, the in vitro activity of Evusheld against SARS-CoV-2 VOCs was evaluated. Results: The cohort was composed of 72 immunocompromised patients. The serum neutralizing activity of tixagevimab/cilgavimab-treated patients was notably lower against newer variants such as BQ.1, XBB.1.5, XBB.1.16, and EG.5. Then, the in vitro study detailed specific EC50 values to quantify the activity of tixagevimab/cilgavimab against various SARS-CoV-2 VOCs. Newer variants like BQ.1 and XBB.1.5 exhibited notably lower neutralization, underscoring the challenges in effectively countering the evolving virus. Interestingly, tixagevimab/cilgavimab maintained reduced but still valid activity against EG.5 with an EC50 of 189 ng/mL and Cmax/EC90 of 110.7. Conclusions: Tixagevimab/cilgavimab efficacy wanes against novel subvariants. This underscores the critical need for ongoing adaptation and vigilance in prophylactic strategies to effectively counter the dynamic and unpredictable nature of the COVID-19 pandemic.

Abstract The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including

Kaposi Sarcoma (KS) is still common among people living with HIV (PLWH). A lot of literature illustrated risk factors associated with KS occurrence, while the aim of our study is to investigate possible factors influencing 5-year survival.

Vibrio cholerae represents diverse species and includes pathogenic and non-pathogenic variants. Particularly serogroups O1 and O139 are related to cholera epidemics, while non-O1/O139 serogroups (NOVC) in general are non-pathogenic or asymptomatic colonizers in humans, but also can cause different diseases. Vibrio albensis, a non-O1/non-O-139 serogroup, is rarely implicated in human infections. Only a few cases of human pathology related to this species are described in the literature. We present the menagement of V. albensis gastroenteritis in a a 47-year-old woman and discuss clinical presentation, diagnosis and treatement.

Abstract A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.

Background: This study aims to investigate the activity of the remdesivir–nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir–nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h, with an HSA score of 52.8 and 28.6, respectively (p < 0.0001). These data were confirmed by performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab and dexamethasone, with an excellent clinical–radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir until she tested negative. Conclusions: Remdesivir–nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

Background and Objective: In patients with mild-to-moderate COVID-19 and at high risk of progression, casirivimab/imdevimab and bamlanivimab/etesivimab were utilized in Umbria from late April to November 2021. This period was characterized by an initial prevalence of alpha (B1.1.1.7) and its progressive substitution with the delta variant (B1.617.2). Many delta infections occurred in patients already recently vaccinated. Our study aimed to observe the clinical outcome of patients treated with mAbs associations in a subgroup in which viral isolation was obtained, the pre and post-infusion neutralizing antibody activity against their viral isolate. Methods: In this retrospective observational study, the clinical outcome before and 30 days after infusion, the baseline neutralizing activity of sera against their viral isolate, and the titers of neutralizing antibodies (NAbTs) one-hour post-infusion relative to the type of mAbs associations were evaluated. Results: Better efficacy of the mAbs combinations relative to monotherapy regarding global hospitalization (p = 0.021) and 30 days symptoms (p

Objectives: The aim of this study was to report on in vitro tests of antibacterial activity of ceftazidime/avibactam in combination against planktonic or biofilm KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), the rate of KPC-Kp blood isolates in University of Perugia Hospital over a 5-year period, and their antimicrobial susceptibility patterns. Methods: The antibacterial activity of ceftazidime/avibactam in combination with other antimicrobials was assessed against planktonic and biofilm bacteria by Etest and checkerboard assay. A retrospective review of laboratory data was performed to evaluate the rate of KPC-Kp from blood samples and their antimicrobial susceptibility patterns. Results: Between 2014 and 2019, 130/4241 (3.1%) KPC-Kp were identified from blood cultures. Their rate increased from 2.3% in 2014–2015 to 4.5% over the last 3 years. Overall, 4.6% (6/130) of KPC-Kp isolates were susceptible to meropenem, 65.4% (85/130) to colistin, 65.1% (84/129) to tigecycline, 34.6% (45/130) to amikacin, 36.2% (42/116) to gentamicin, 40.2% (39/97) to fosfomycin and 91.5% (65/71) to ceftazidime/avibactam. Five of six ceftazidime/avibactam-resistant KPC-Kp were isolated from patients not treated with ceftazidime/avibactam. Synergism was detected both by Etest and checkerboard assay for the combination of ceftazidime/avibactam plus meropenem against planktonic isolates, whilst lower bactericidal activity was observed in biofilm KPC-Kp isolates. Conclusions: Our in vitro data suggest that the combination of ceftazidime/avibactam plus meropenem has a synergistic antibacterial activity against planktonic bacteria, whilst a lower activity was detected against biofilm, suggesting worse clinical outcomes whenever biofilm infections are present. Further analyses are required to confirm these results before extending them to clinical practice.

Abstract Background Tobacco use is a leading cause of preventable diseases and death for all individuals, even more so for people living with HIV (PLWH), due to their status of chronic inflammation. To date, in Italy no study was performed to compare smoking habits in PLWH and the general population. We aimed to investigate smoking habits in PLWH, as compared to the general population. Methods Multi-center cross-sectional study. Smoking habits were compared between PLWH and the general population. PLWH were enrolled in the STOPSHIV Study. The comparison group from the general population was derived from a survey performed by the National Statistics Institute (ISTAT), with a stratified random sampling procedure matching 2:1 general population subjects with PLWH by age class, sex, and macro-area of residence. Results The total sample consisted of 1087 PLWH (age 47.9 ± 10.8 years, male 73.5%) and 2218 comparable subjects from the general population. Prevalence of current smokers was 51.6% vs 25.9% (p 20 cigarettes per day) (aOR = 4.84; 95% CI = 3.74–6.27; p

Objectives: Ceftobiprole is a relatively new cephalosporin with broad-spectrum activity and good tolerability. Despite its promising characteristics, to our knowledge, only two case reports, previously published also by some of us, is available concerning its administration for the treatment of infective endocarditis. Hereby we report our experience in this field. Methods: All the patients with infective endocarditis treated with ceftobiprole were enrolled. Results: 12 cases of endocarditis were treated with ceftobiprole, 11/12 in combination with daptomycin and 1/12 as monotherapy. Gram-positive bacteria were isolated in 12/12 patients; 3 cases were polymicrobial. Cure rate was 83% (10/12 patients). In 9/12 (75%) cases, patients were switched to ceftobiprole following failure of previous antimicrobial regimen. In 3/3 patients in which ceftobiprole was administered because of persistently positive blood culture, bacteraemia clearance was rapidly achieved. Conclusions: Ceftobiprole, especially in combination, could be a promising alternative treatment for infective endocarditis.

Background: Infective endocarditis (IE) is still a severe disease with elevated morbidity and mortality. Nevertheless, the last European guidelines (GL) date back to 2015, and a recent survey described a diffuse suboptimal adherence to their recommendations. Here, we described a real-life scenario about adherence to IE treatment GL. Methods: This was a retrospective, multicentric, case–control study. All the cases of IE admitted to our wards from 2016 to 2020 were enrolled. Patients were divided into two groups, according to the non-adherence (group A, cases) or adherence (group B, controls) to 2015 ESC guidelines. Only targeted treatments were considered. Groups were compared for demographic, clinical, microbiological, and laboratory data and outcome. As a post hoc analysis, we analysed the characteristics of deviations from the guidelines and how these deviations affected mortality. Results: A total of 246 patients were enrolled, with 128 (52%) in group A and 118 (48%) in group B. Groups were homogeneous except for aetiologies: staphylococcal and blood-culture-negative IE were more frequent in group A, while streptococcal and enterococcal IE were more frequent in group B (p < 0.001). In-hospital mortality was comparable in the two groups. The most frequent causes of deviations from the guidelines were use of daptomycin, in addition to standard treatments and the missing administration of rifampin or gentamycin. Conclusions: Adherence to 2015 ESC guidelines was limited but it did not affect mortality.

After almost three years of the pandemic, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is still spreading around the world, causing notable sanitary and social issues. New antiviral therapies are constantly under investigation. However, few options have been approved for the treatment of COVID-19. Clinical trials are currently ongoing to evaluate the efficacy of nelfinavir on mild–moderate COVID-19. This study aims to investigate the activity of this compound on SARS-CoV-2 “Variants of Concern” (VOCs), comparing its effectiveness with the approved drugs remdesivir and molnupiravir. The experiments were conducted in a biosafety level 3 facility. In this study, we used a Vero-E6-cell-based infection assay to investigate the in vitro activity of nelfinavir, molnupiravir, and remdesivir. Four strains of SARS-CoV-2 were tested: 20A.EU1, B.1.1.7, P.1, and B.1.617.2. All compounds reached micromolar/submicromolar EC50, EC90, and EC99. Furthermore, the Cmax/EC50 and Cmax/EC90 ratios were >1 for all compounds and all variants tested. Our study demonstrated that nelfinavir, as molnupiravir, and remdesivir are effective in vitro on SARS-CoV-2 variants.

Background and Objective The use of monoclonal antibodies to the SARS-Cov-2 spike protein for early treatment of COVID-19 disease is being evaluated, with only phase 2 studies available, to date. Emergency authorization of bamlanivimab monotherapy was get in November 2020 by the FDA and in March 2021 by italian agency AIFA. Its use was then revoked in April 2021 by both. This study reports the results of bamlanivimab utilization in monotherapy in Umbria (Italian region), in order to verify whether, in a population with multiple risk factors, comparable results to phase 2 BLAZE1 trial had been obtained. Methods Retrospective observational study, between March and April 2021, in patients treated with bamlanivimab was performed. Demographic and clinical characteristics before and after infusion were evaluated. Moreover, a telephone interview about 30 days after the infusion was carried out to evaluate the overall course. Results All patients had an early infection (mean 4±1.73 days), almost all by alpha variant (97%). No adverse events to treatment were observed. Altogether within 30 days, the hospitalization rate was 20%, 15% for COVID-19 related pathologies , versus 4% at 11 days in BLAZE1 phase 2 study. Worsening of some symptoms observed at baseline such as asthenia (77 vs 51.3%), shortness of breath (38 vs 23%) was registered, as well as the onset of non-restorative sleep (41%). Conclusions The clinical outcome after bamlanivimab monotherapy was far below the expectation despite the patients had been infected by a theoretically sensitive viral variant.

Viral infections sustain their replication cycle promoting a pro-oxidant environment in the host cell. In this context, specific alterations of the levels and homeostatic function of the tripeptide glutathione have been reported to play a causal role in the pro-oxidant and cytopathic effects (CPE) of the virus. In this study, these aspects were investigated for the first time in SARS-CoV2-infected Vero E6 cells, a reliable and well-characterized in vitro model of this infection. SARS-CoV2 markedly decreased the levels of cellular thiols, essentially lowering the reduced form of glutathione (GSH). Such an important defect occurred early in the CPE process (in the first 24 hpi). Thiol analysis in N-acetyl-Cys (NAC)-treated cells and membrane transporter expression data demonstrated that both a lowered uptake of the GSH biosynthesis precursor Cys and an increased efflux of cellular thiols, could play a role in this context. Increased levels of oxidized glutathione (GSSG) and protein glutathionylation were also observed along with upregulation of the ER stress marker PERK. The antiviral drugs Remdesivir (Rem) and Nelfinavir (Nel) influenced these changes at different levels, essentially confirming the importance or blocking viral replication to prevent GSH depletion in the host cell. Accordingly, Nel, the most potent antiviral in our in vitro study, produced a timely activation of Nrf2 transcription factor and a GSH enhancing response that synergized with NAC to restore GSH levels in the infected cells. Despite poor in vitro antiviral potency and GSH enhancing function, Rem treatment was found to prevent the SARS-CoV2-induced glutathionylation of cellular proteins. In conclusion, SARS-CoV2 infection impairs the metabolism of cellular glutathione. NAC and the antiviral Nel can prevent such defect in vitro.

Abstract Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.

Abstract Background Among people living with HIV (PLWH), the prevalence of non-HIV related co-morbidities is increasing. Aim of the present study is to describe co-morbidity and multi-morbidity, their clustering mode and the potential disease-disease interactions in a cohort of Italian HIV patients. Methods Cross-sectional analysis conducted by the Coordinamento Italiano per lo Studio di Allergia e Infezioni da HIV (CISAI) on adult subjects attending HIV-outpatient facilities. Non-HIV co-morbidities included: cardiovascular disease, diabetes mellitus, hypertension, oncologic diseases, osteoporosis, probable case of chronic obstructive pulmonary disease (COPD), hepatitis C virus (HCV) infection, psychiatric illness, kidney disease. Multi-morbidity was defined as the presence of two or more co-morbidities. Results One thousand and eighty-seven patients were enrolled in the study (mean age 47.9 ± 10.8). One hundred-ninety patients (17.5%) had no co-morbidity, whereas 285 (26.2%) had one condition and 612 (56.3%) were multi-morbid. The most recurrent associations were: 1) dyslipidemia + hypertension (237, 21.8%); 2) dyslipidemia + COPD (188, 17.3%); 3) COPD + HCV-Ab+ (141, 12.9%). Multi-morbidity was associated with older age, higher body mass index, current and former smoking, CDC stage C and longer ART duration. Conclusions More than 50% of PLHW were multi-morbid and about 30% had three or more concurrent comorbidities. The identification of common patterns of comorbidities address the combined risks of multiple drug and disease-disease interactions.

SARS-CoV-2 is constantly evolving, leading to new variants. We analysed data from 4400 SARS-CoV-2-positive samples in order to pursue epidemiological variant surveillance and to evaluate their impact on public health in Italy in the period of April–December 2021. The main circulating strain (76.2%) was the Delta variant, followed by the Alpha (13.3%), the Omicron (5.3%), and the Gamma variants (2.9%). The B.1.1 lineages, Eta, Beta, Iota, Mu, and Kappa variants, represented around 1% of cases. There were 48.2% of subjects who had not been vaccinated, and they had a lower median age compared to the vaccinated subjects (47 vs. 61 years). An increasing number of infections in the vaccinated subjects were observed over time, with the highest proportion in November (85.2%). The variants correlated with clinical status; the largest proportion of symptomatic patients (59.6%) was observed with the Delta variant, while subjects harbouring the Gamma variant showed the highest proportion of asymptomatic infection (21.6%), albeit also deaths (5.4%). The Omicron variant was only found in the vaccinated subjects, of which 47% had been hospitalised. The diffusivity and pathogenicity associated with the different SARS-CoV-2 variants are likely to have relevant public health implications, both at the national and international levels. Our study provides data on the rapid changes in the epidemiological landscape of the SARS-CoV-2 variants in Italy.

Abstract Background and aims Eradication of the hepatitis C virus (HCV) may affect proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and cardiovascular risk. However, information regarding PCSK9 level after HCV eradication is lacking. Hence, in this case‐control retrospective study, we aimed to evaluate PCSK9 level from pretherapy baseline up to sustained virological response (SVR). Methods Eighty‐four patients treated with directly acting antivirals (DAAs) between July 2015 and May 2018 were enrolled. Differences in baseline PCSK9 level due to absence/presence of recorded baseline characteristics (covariates) were evaluated. Changes in PCSK9 levels from pretherapy to SVR (ΔPCSK9) and their correlations with the covariates were assessed. The repeated measures analysis of variance was used to investigate the differences in PCSK9 level from the baseline to the achievement of SVR due to absence/presence of any covariate. Results The mean age of the patients was 67.6 ± 11 years, and 53.6% were males. Baseline PCSK9 levels were statistically lower in patients using statins than in those not using statins (mean, 70.3 ± 43.1 ng/mL vs 271.8 ± 252.2 ng/mL; P = .017). PCSK9 level decreased significantly from baseline to the time of SVR (255 ± 248 ng/mL vs 169 ± 188 ng/mL; P

Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients. Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (

Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic; however, the need for orally administered antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using five two-fold serial dilution of compound concentrations ≤EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were performed in triplicate, each being repeated at least three times. The synergistic score was calculated using Synergy Finder version 2. Results: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p < 0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p < 0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p = 0.01) and 13.08 (p < 0.0001), respectively. Conclusion: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro.

Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild-type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD), and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID50) and drug concentration (IC50), respectively, showing 50% protection of virus-induced cytopathic effect. All pre-infusion sera were negative for SARS-CoV-2 neutralizing activity. BAM/ETE, CAS/IMD, and SOT showed activity against the WT (ID50 6295 (4355–8075) for BAM/ETE; 18,214 (16,248–21,365) for CAS/IMD; and 456 (265–592) for SOT) and the delta (14,780 (ID50 10,905–21,020) for BAM/ETE; 63,937 (47,211–79,971) for CAS/IMD; and 1103 (843–1334) for SOT). Notably, only SOT was active against BA.1 (ID50 200 (37–233)), whereas BA.2 was neutralized by CAS/IMD (ID50 174 (134–209) ID50) and SOT (ID50 20 (9–31) ID50), but not by BAM/ETE. No significant inter-variant IC50 differences were observed for molnupiravir (1.5 ± 0.1/1.5 ± 0.7/1.0 ± 0.5/0.8 ± 0.01 μM for WT/delta/BA.1/BA.2, respectively), nirmatrelvir (0.05 ± 0.02/0.06 ± 0.01/0.04 ± 0.02/0.04 ± 0.01 μM) or remdesivir (0.08 ± 0.04/0.11 ± 0.08/0.05 ± 0.04/0.08 ± 0.01 μM). Continued evolution of SARS-CoV-2 requires updating the mAbs arsenal, although antivirals have so far remained unaffected.

The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In light of the urgent need to identify novel approaches to be used in the emergency phase, we have embarked on an exploratory campaign aimed at repurposing natural substances and clinically available drugs as potential anti-SARS-CoV2-2 agents by targeting viral proteins. Here we report on a strategy based on the virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike's protein receptor binding domain (RBD). By combining an in silico approach and molecular in vitro testing we have been able to identify several triterpenoid/steroidal agents that inhibit interaction of the Spike RBD with the carboxypeptidase domain of the Angiotensin Converting Enzyme (ACE2). In detail, we provide evidence that potential binding sites exist in the RBD of the SARS CoV-2 Spike protein and that occupancy of these pockets reduces the ability of the RBD to bind to the ACE2 consensus in vitro. Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivatives such as glyco-ursodeoxycholic acid and semi-synthetic derivatives such as obeticholic acid reduces the RBD/ACE2 binding. In aggregate, these results might help to define novel approaches to COVID-19 based on SARS-CoV-2 entry inhibitors.

Staphylococcus aureus infections associated with implanted medical devices are difficult to treat and require long-lasting antibiotic therapies, especially when device removal is not possible or easy such as in the case of joint prostheses. Biofilm formation is a major cause of treatment failure and infection recurrence. This study aimed to test, for the first time, the in vitro combination of tedizolid plus rifampicin on methicillin-sensitive (MSSA ATCC 6538) and methicillin-resistant (MRSA ATCC 43300) S. aureus mature biofilm. Here, we demonstrated that the combination of tedizolid with rifampicin significantly disaggregated pre-formed biofilm of both strains, reduced their metabolic activity and exerted bactericidal activity at clinically meaningful concentrations. Notably, tedizolid was able to completely prevent the emergence of resistance to rifampicin. Moreover these effects were similar to those obtained with daptomycin plus rifampicin, a well-known and widely used combination. Preliminary results on some MRSA clinical isolates confirmed the efficacy of this combination in reducing biofilm biomass and preventing rifampicin resistance onset. Further in vivo studies are needed to confirm the validity of this promising therapeutic option that can be useful against biofilm-associated S. aureus infections.

We report a case of a 33-year-old Italian pregnant at 40 weeks of gestation affected by asymptomatic SARS-CoV-2 infection delivering a healthy baby with no evidence of Coronavirus Disease 2019 (COVID-19). Vaginal delivery was uncomplicated, the breastfeeding was permitted under strict measures of infection control. The breast milk was negative for SARS-CoV-2. Control at 7 and 15 days indicated mother and baby good clinical condition, no signs of neonatal infection demonstrated by news oropharyngeal and rectal swab test negative for SARS-CoV-2.

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF–platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.

Borrelia crocidurae is endemic in West Africa, where it represents the leading cause of tick-borne relapsing fever (TBRF). TBRF typically presents with high fever and systemic symptoms, followed by recurrent episodes. Neurological complications may occur during febrile relapses. B. crocidurae is considered the most neurotropic agent of TBRF and is associated to severe neurological manifestations i.e. meningitis and encephalitis.To date, European cases of B. crocidurae infection have been reported in travelers returning from endemic areas. We report the first autochthonous case in Europe of B. crocidurae infection, presenting as meningitis with cranial polyneuritis and cavernous sinus thrombosis that were not preceded by classic febrile recurrences. Keywords: Borrelia crocidurae, Europe, Autochthonous, Meningitis, Cranial polyneuritis, Cavernous sinus thrombosis

Abstract Background Renal dysfunction is a common problem in the HIV+ population, due to the effect of both the HIV virus and the several classes of ARV drugs such as tenofovir (TDF). It is also known that the presence of renal damage correlates with cardiovascular risk and therefore with the risk of mortality of the patients accordingly. The detection of early renal damage is very important. Albuminuria and microalbuminuria are markers of early kidney disease and cardiovascular risk. The aim of the study is to evaluate the prevalence of microalbuminuria in a large polycentric sample, of unselected and consecutive HIV-patients followed as outpatients, and to assess its association with different therapeutic regimens. Methods We studied 326 patients with a mean age of 48.4 ± 1.6 years, treated at the Infectious Diseases Clinics of Chieti and Perugia for 48 weeks. The main metabolic parameters and the microalbuminuria levels in a single sample of urine were evaluated. Results Microalbuminuria was detected in 61.0% of patients at T0 and in 49.7% after 48 weeks of observation with a median values of 1.1 mg/L (IQR: 0-2.7) vs. 0 mg/L (IQR: 0-2.0). 70% of the enrolled population did not show changes in microalbuminuria levels over time, 19% showed improvement, and 11% of the population had a worsening of microalbuminuria levels without any alteration of creatinine, uric acid and GFR-MDRD. We also found a statistically significant association between the development of microalbuminuria and gender (p

Background: There is limited information on pregnancy loss in women with HIV, and it is still debate whether HIV-related markers may play a role. Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. Methods: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (

The aim of this study was to establish the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on inanimate surfaces such as plastic, stainless steel, and glass during UV-C irradiation which is a physical means commonly utilized in sanitization procedures. The viral inactivation rate, virus half-life, and percentage of titer reduction after UV-C irradiation were assessed. Infectivity was maintained on plastic and glass until 120 h and on stainless steel until 72 h. The virus half-life was 5.3, 4.4, and 4.2 h on plastic, stainless steel, and glass, respectively. In all cases, titer decay was >99% after drop drying. UV-C irradiation efficiently reduced virus titer (99.99%), with doses ranging from 10.25 to 23.71 mJ/cm2. Plastic and stainless steel needed higher doses to achieve target reduction. The total inactivation of SARS-CoV-2 on glass was obtained with the lower dose applied. SARS-CoV-2 survival can be long lasting on inanimate surfaces. It is worth recommending efficient disinfection protocols as a measure of prevention of viral spread. UV-C can provide rapid, efficient and sustainable sanitization procedures of different materials and surfaces. The dosages and mode of irradiation are important parameters to consider in their implementation as an important means to fight the SARS-CoV-2 pandemic.

Myocarditis is an inflammatory disease of the myocardium. Viruses, such as enterovirus, adenovirus, parvovirus B19, HHV6 or cytomegalovirus (CMV) and autoimmune diseases are recognized causes of myocarditis. We describe the clinical case of a young Indian woman with SLE and a concomitant acute CMV related myocarditis with favourable outcome after ganciclovir therapy.CMV myocarditis may range from being a subclinical infection with incidental findings on ECG to a life threating presentation. There are no trials demonstrating the efficacy of antiviral therapy in myocarditis. Case series of patients with CMV myocarditis have reported an excellent clinical outcome after antiviral agents. Lupus Myocarditis (LM) is more prevalent in young females. There are no specific ECG or echocardiographic signs. Treatment strategies of LM are based on corticosteroids, immunosuppressive agents and cardiovascular support, usually with a favorable prognosis, but LM often lead to a severe clinical picture, with mortality of 10.3%. Endomyocardial biopsy (EBM) is recommended as the gold standard but it is very underused in clinical practice, It should be performed in a specialized center but there are concerns on lack of specificity, low negative predictive value, risk of complication, and sampling errors due to the focal nature of myocarditis. Both SLE and CMV are potentially responsible of acute myocarditis. In our knowledge, CMV myocarditis with SLE was described in only one other patient. The initiation of antiviral therapy improved the clinical picture and, in our opinion, it is mandatory when CMV related life threating conditions develop. Keywords: Myocarditis, Cytomegalovirus, Systemic lupus erythematosus

Background and aimsWe investigated the conditioning roles of viral tropism and other variables on plasma HIV RNA levels after 6 months of combination antiretroviral therapy (cART) in an HIV-infected Italian naïve population using regression tree, random forest regression, and path analysis (PA). Patients in this multicenter observational study were treated with all antiviral drugs that are currently recommended as first-line therapies.MethodsAdult patients with chronic HIV infection were enrolled at the beginning of first-line cART (T0). The main variables were age, gender, tropism, "lcd4_0" and "lcd4_6" (log10 CD4+counts at T0 and after 6 months of cART, respectively), and "lrna0" (log10 HIV RNA at T0). Regression tree and random forest analyses were applied. The predictive effect on lrna6 (log10-transformed plasma HIV RNA after 6 months of cART) was also investigated via PA (x4->lcd4_0->lrna0->lrna6) with a treatment selection step included as a dependent (mediator) variable for each third drug and, as predictive covariates, age, female, x4_10, x4_5, lcd4_0, and lrna0. Tropism was assessed in plasma using the Geno2pheno algorithm with 2 false positive rate (FPR) cut-offs: 5% (x4_5) and 10% (x4_10).ResultsThe study included 571 subjects (21% x4_10 and 10.7% x4_5). The only important predictor of lrna6 was lrna0, and a positive indirect effect of bearing X4 virus in plasma was suggested. A significant direct positive effect of protease inhibitors on lrna6 was found (p = 0.022), and a significant negative effect of integrase strand transfer inhibitor (INSTI) was also detected (p = 0.003 for FPR ≤ 5% and p = 0.01 for FPR < 10%). PA predicted mean residual viremias of 40 copies/mL without INSTI and 3 copies/mL with INSTI.ConclusionsPA indicated a possible indirect role of HIV tropism on lrna6 with both FPR < 10% and ≤ 5%. Patients treated with INSTI had a predicted residual viremia of 3 copies/mL.

BACKGROUND:Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. METHODS:Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/μL in raltegravir and 239 cells/μL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. CONCLUSIONS:Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/μL at week 48. TRIAL REGISTRATION:EUDRACT number: 2011-005973-21.

Surgical site infections (SSIs) are the most common healthcare-associated infections. The appropriate use of Surgical Antibiotic Prophylaxis (SAP) is a key component to reduce SSIs, while its inappropriate application is a major cause of some emerging infections and selects for antibiotic resistance. We describe an Antimicrobial Stewardship (AMS) intervention on SAP appropriateness. The prospective study was conducted in an Italian hospital, in 12 main surgical units, and was organized in three subsequent phases, as follows. Phase 0: Definition of hospital evidence-based guidelines and a new workflow to optimize the process of ordering, dispensing, administering and documenting the SAP. Phase 1: We analysed 2059 elective surgical cases from January to June 2018 for three SAP parameters of appropriateness: indication, choice and dose. Phase 2: In July 2018, an audit was performed to analyse the results; we reviewed 1781 elective surgical procedures from July to December 2018 looking for the same three SAP appropriateness parameters. The comparative analysis between phases 1 and 2 demonstrated that the correct indication, the correct dose and the overall compliance significantly improved (p-value 0.00128, p-value < 2.2·1016 and p-value < 5.6·1012 respectively). Our prospective study demonstrates a model of successful antimicrobial stewardship intervention that improves appropriateness on SAP.

Listeria monocytogenes (LM) is an opportunistic pathogen, and the most common central nervous system manifestation is meningitis while listerial brain abscesses are rare. We describe 2 cases of brain abscess due to LM and a literature review. Only 73 cases were reported in the literature from 1968 to 2017. The mean age was 51.9, and the mortality rate was 27.3%. In 19% of cases, no risk factors for neurolisteriosis were identified. Blood cultures were positive in 79.5% while CSF or brain abscess biopsy material was positive in 50.8%. In 40% was started a monotherapy regimen while in 60% a combination therapy without substantial differences in mortality. Fifty-two percent underwent neurosurgery while 45.3% has been treated only with medical therapy. The mortality rates were, respectively, 13% and 38.2%. Only 25% of patients who were treated for ≤6 weeks underwent neurosurgery, while 80% of those who were treated for ≥8 weeks were operated. The mortality rates were, respectively, 12.5% and 0%, suggesting that a combined approach of surgery and prolonged medical therapy would have an impact on mortality. We believe that it is essential to carry out this review as brain abscesses are rare, and there are no definitive indications on the optimal management, type, and duration of therapy.