Background: The relationship between diet and body composition in people with HIV (PWH) is still not well defined. Therefore, our primary objective was to assess the association between Mediterranean diet (MD) adherence and body composition measured by whole-body dual-energy X-ray absorptiometry (DXA). Secondly, we aimed to assess differences between people living in the north (Padua, Veneto Region, Italy) vs. those living in the south of Italy (Catanzaro, Calabria Region, Italy) and with respect to ethnicity. Methods: In this cross-sectional study, adults with HIV with a confirmed virological suppression were enrolled at two Italian HIV clinics. MD adherence was assessed using the validated MedDiet Score, with high adherence being defined as a score ≥ 25. All participants underwent whole-body DXA. Anthropometric and DXA-derived measures were compared between people with high vs. low adherence to MD, and multivariable linear regression adjusted for age, sex, and CD4+ count at nadir was performed. Results: Among 130 participants (81.5% male; median age 57 years), 105 (80.8%) showed high MD adherence. High adherence to MD was more common among participants from Southern Italy than among those from Northern Italy and was associated with Caucasian ethnicity, higher education, higher CD4+ count and CD4/CD8 ratio, and a lower prevalence of obesity and neurological disorders. DXA analyses showed lower total and trunk fat mass and higher lumbar spine bone mineral density in highly adherent individuals. After adjustment, high MD adherence remained independently associated with lower BMI (β −5.3, 95% CI −7.3 to −3.4; p < 0.001). Conclusions: In ageing PWH, high MD adherence was associated with a more favourable clinical profile and healthier body composition, particularly lower central adiposity and BMI. Prospective and interventional studies are needed to clarify the role of this type of diet in PWH.

Infections are a leading cause of morbidity, mortality, and treatment delays in AML and APL. While international guidelines emphasize intensive chemotherapy, they often overlook less intensive regimens, rely on outdated data, and ignore rising MDR infections. A GIMEMA survey across Italian centers revealed significant heterogeneity in antimicrobial prophylaxis, and vaccination practices. An expert panel reviewed 2012-2025 English literature with focus on infections via Delphi/nominal group methods, achieving ≥70% consensus. Prophylaxis with fluoroquinolones showed low agreement (28%) for intensive chemotherapy and venetoclax-based regimens due to no survival benefit, MDR pressure and microbiota disruption; not recommended for low-intensity/palliative care. Posaconazole is advised for intensive chemotherapy with or without FLT3 inhibitors, venetoclax-based regimens, HMA with or without ivosidenib (first 4 cycles), but not APL/palliative care. Antiviral prophylaxis is recommended for APL receiving arsenic trioxide; limited evidence elsewhere. The panel supports universal pneumococcal, influenza, SARS-CoV-2 and herpes zoster vaccination. Overall, these consensus statements aim to harmonize practice and highlight key areas requiring specifically designed prospective studies.

INTRODUCTION:Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with high morbidity and mortality rates. Furthermore, the role of CRAB respiratory colonization, including multisite colonization, has not yet been adequately highlighted in critically ill patients. MATERIALS AND METHODS:In this retrospective multicenter study, conducted in 4 different Italian hospitals, patients with CRAB respiratory colonization +/- other site who developed or did not develop clinically significant pneumonia from December 2015 to December 2023 were enrolled. The primary objective of the study was to identify risk factors associated with the development of pneumonia. RESULTS:760 patients were enrolled; among them, 392 (51.5%) developed pneumonia, while 304 (39.9%) patients presented multisite colonization. Overall, in-hospital mortality was 76.3% with a higher mortality (79.6%) in patients who developed pneumonia (p = 0.033). In logistic regression analysis, factors associated with the development of pneumonia included: age, immunosuppressive therapy, COPD, ventilatory support and multisite colonization. A score was developed with AUC 0.72, CI95% 0.68-0.75, p < 0.001 and a sensitivity of 79% and specificity of 55% with a score > 2 and a maximum score of 10 points. Multisite colonization was recorded more frequently in patients who developed pneumonia (51%, p < 0.001). Finally, Kaplan-Meier curves showed a significantly reduced survival at 30 days (p = 0.005) and throughout the hospital stay (p = 0.002) in patients with multisite colonization. CONCLUSIONS:This study highlights the risk factors associated with the development of pneumonia in patients already colonized by CRAB. Multisite colonization showed an important role as a risk factor for the development of pneumonia and for its correlation with mortality. CLINICAL TRIAL NUMBER:Not applicable.

Immunocompromised (IC) patients face significant challenges in managing COVID-19 due to their heightened susceptibility to severe illness, persistent infections, and the potential development of drug resistance. Studies indicate that IC patients, particularly those with hematologic malignancies (HM), hematopoietic stem cell transplants (HSCTR), or solid organ transplants (SOTR), experience higher mortality rates and worse outcomes compared to the general population, even post-vaccination. The persistence of the virus in these patients, combined with its rapid mutation, further complicates treatment. Recent evidence supports the use of combined neutralizing monoclonal antibodies (mAbs) and direct-acting antivirals (DAAs) as a more effective approach to viral clearance, reducing mortality, and preventing relapses. However, the rise of resistant variants, especially to mAbs, and concerns about the safety of prolonged or intensive therapies pose ongoing challenges. Monotherapies often fail short to address these issues, highlighting the need for early combined therapy (ECT) with mAbs and DAAs. ECT has shown promise in managing COVID-19 in IC individuals by targeting multiple stages of the viral lifecycle, reducing viral load, and clearing infections at earlier stages, which helps mitigate the risks of severe disease and drug resistance. Continued research is essential to refine these treatment protocols, especially as the virus evolves. Although further studies are needed, current findings suggest that ECT may become the standard of care for managing COVID-19 in severely IC patients, offering better clinical outcomes and hindering viral persistence.

The global rise in infections due to multidrug-resistant Gram-negative bacteria (MDRGNB) infections has disproportionately impacted immunocompromised (IC) hosts. Cefiderocol, a novel siderophore cephalosporin, exhibits potent activity against MDRGNB, but limited data exist on its use in IC patients. This study aimed to describe cefiderocol use in IC patients. Patients and therapy characteristics were descriptively reported, and outcomes were compared between IC and non-IC patients. Cox regression models were used to identify factors associated with mortality. Among 185 patients, 84 (45.4

Tuberculosis (TB) remains a significant global health challenge, with the World Health Organization (WHO) aiming for a 95% reduction in TB deaths by 2030. Disparities in TB detection persist, particularly regarding gender, immigration status, and resistance patterns. In Calabria, Italy-a key entry point for migrants from highTB-incidence regions-TB poses a notable public health risk. This multicenter, retrospective study examines newly diagnosed TB cases in Calabria from 2012 to 2023, focusing on rifampicin-resistant TB (RR-TB). During this period, 800 TB cases were diagnosed, with 270 (33.7 %) in native-born Italians and 530 (66.2 %) in foreign-born individuals, showing significant differences in age (p < 0.001) and gender (p = 0.013). Among 685 patients of this cohort with available HIV status, 24 (3.5 %) were people living with HIV (PLWH), primarily from Africa, and diagnosed at higher rates of RR-TB (p < 0.001). TB cases varied by province, correlating with specific birthplaces. A total of 27 (3.4 %) RR-TB cases were identified, with heightened resistance to multiple drugs. Among these strains, 20 (74.1 %) were isoniazid-resistant (MDR-TB). This study underscores the need for comprehensive TB control strategies, especially regarding co-infection with HIV and the emergence of drug-resistant strains, emphasizing the importance of early detection and tailored management in Southern Italy.

Abstract Background Gastrointestinal Infections (GIs) pose a significant challenge in patients with inflammatory bowel diseases (IBD), complicating its management and triggering IBD relapses. The overlap in clinical symptoms makes complex differentiating GIs from IBD flares, impacting therapeutic decisions. This study aims at evaluating the long-term impact of GIs in IBD patients. Methods From January 2020 to September 2024, 102 IBD patients (mean age 45±16 yrs; 78 ulcerative colitis, UC and 24 Crohn’s disease, CD) experiencing a clinical relapse according to ECCO guidelines, were retrospectively evaluated. GIs were established via stool immunochromatography and multiplex molecular assay. Demographic, clinical and laboratory findings along with the treatment were noticed at the time of flare, 6 and 12 months later. Statistical analysis was performed by Mann-Witney and chi-square test as appropriate (p<0.05). Results Nineteen patients tested GIs positive (GIs+): 14 out of 78 (18%) UC and 5 out of 24 CD (21%) patients. Clostridium difficile infection (CDI) was found in 11 patients while non-CDI enteric pathogens (EP+) in the remaining 8 patients. All CDI patients received a first-line antibiotic treatment while no treatment was offered to EP+ patients. By stratifying for GIs at the flare time, there were no differences between GIs+ and GIs- patients with regard to age (45±16 vs46±17 yrs, p=ns), disease duration (11±9 vs 12±10 yrs, p=ns), disease activity score (Mayo score 5±2 vs 5±2, p=ns and Harvey Bradshaw index 8±4 vs 8±4, p=ns) and inflammation biomarkers (C-reactive protein 21±41 vs 22±42 mg/dl, p=ns and fecal calprotectin 1446±1751 vs 1452±1714 mcg/gr, p=ns). At 12 months after flare, the number of patients being treated with biologics increased only in GIs+ IBD patients, from 3 out 19 (16%) to 10 out 19 (53%) (Figure 1). All the 7 IBD patients who have got biologics were CDI+. Conclusion This study confirms that distinguishing a disease flare from the presence of superimposed GIs remains challenging. Notably, only in patients with CDI there was an increased use of biologics later after the flare onset. This suggest that CDI may serve as a marker of a more aggressive disease course in IBD patients.

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae has become endemic in Europe, including in Italy, where its prevalence has risen dramatically, primarily due to epidemic clones harboring metallo-enzymes. This study aims to investigate the dissemination of K. pneumoniae strains co-producing OXA-48 and NDM-1 between two hospitals in southern Italy using molecular analyses. Methods: A total of 49 K. pneumoniae strains, predominantly co-producing OXA-48 and NDM-1, were collected between March and December 2023. Antibiotic susceptibility testing was conducted following EUCAST guidelines. Whole-genome sequencing (Illumina MiSeq) and bioinformatics tools (CARD, CLC Genomics Workbench) were used to identify resistance and virulence genes, capsule loci, and phylogenetic relationships. Results: All isolates exhibited multidrug-resistant or extensively drug-resistant profiles, including resistance to ceftazidime/avibactam and meropenem/vaborbactam. Genomic analysis revealed diverse resistance genes such as blaOXA-48, blaNDM-1, blaCTX-M-15, and blaSHV variants. Virulence genes associated with capsules, fimbriae, and siderophores were widespread. Most strains were classified as ST147 by MLST and contained various plasmids known to carry antimicrobial resistance. Phylogenetic analysis confirmed their clonal relatedness, highlighting the intra-hospital dissemination of high-risk clones. Conclusions: High-risk K. pneumoniae clones, particularly ST147, pose significant challenges in healthcare settings due to the extensive antimicrobial resistance driven by plasmid-borne resistance genes, including those that co-produce carbapenemases, like blaNDM-1 and blaOXA-48. Molecular monitoring of these clones is essential for improving targeted infection control strategies, mitigating the spread of multidrug-resistant pathogens, and managing their clinical impact effectively.

PURPOSE:Lower respiratory tract infections are reported as one of top five causes of mortality and morbidity in the world. A bacterial etiology is often involved in HAP, most frequently from multidrug resistant gram-negative bacteria, and fast accurate diagnosis of etiologic agent(s) of LRTI is essential for an appropriate management. The aim of this retrospective study was to evaluate the analytical performance of Biofire Filmarray Pneumonia Plus for bacteria detection in bronchoalveolar lavage samples and the concordance of bacterial loads between BFPP and cultural gold standard methods. METHODS:A total of 111 BAL samples were obtained from 111 consecutive patients admitted to Intensive Care Unit of "Renato Dulbecco" Teaching Hospital of Catanzaro, from March 2023 to March 2024. RESULTS:Compared to conventional methods, BFPP showed a sensitivity of 99 % and a specificity of 64 %. The agreement between the two methods was assessed by calculating PPA and NPA, being 89 % and 95 %, respectively. The most common bacterial species identified at BFPP was Klebsiella pneumoniae, followed by Acinetobacter calcaceuticus-baumanii complex, Staphylococcus aureus and Pseudomonas aeruginosa. Bacterial load (CFU/ml) in relation to copy number detected by molecular analysis showed the best performance for value ≥106 copie/mL. About molecular mechanisms of resistance in comparison to phenotypic profiles, the highest level of performance was observed for presence of KPC genes, all isolates showing resistance to carbapenems, followed by OXA-48 like and NDM. CONCLUSION:The high concordance reported in this study between the identification of resistance genes and phenotypic indication can lead to an appropriate, fast and tailored antibiotic therapy.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

BACKGROUND:Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections. METHODS:This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. RESULTS:One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success. CONCLUSIONS:Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB.

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. In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Cefiderocol was administered as empirical and targeted therapy in 27.5

It is estimated that antimicrobial resistance (AMR) is responsible for nearly 5 million human deaths worldwide each year and will reach 10 million by 2050. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. Among the antibiotics under consideration, Sulbactam/durlobactam seems to be the best candidate to replace current back-bone agents. Cefiderocol could play a pivotal role within combination therapy regimens. Due to toxicity and the pharmacokinetics/pharmacodynamics (PK/PD) limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the efficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with improved lung activity, as well as on the iv rifabutin formulation. In this narrative review, we focused the antibiotic treatment of CRAB infections in view of newly developed β-lactam agents (NBLs).

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, responsible for Coronavirus Disease 2019 (COVID-19), exhibits a spectrum of clinical manifestations, ranging from asymptomatic to severe pulmonary dysfunction or death. The variability in COVID-19 severity has largely been attributed to the host's genetic characteristics, suggesting a polygenic genetic architecture, without significant strong evidence of sex-related genetic differences. In this Italian retrospective case-control study, we investigated the association between COVID-19 severity (severe vs. asymptomatic/oligosymptomatic healed individuals) and HLA gene variants, analyzed by next-generation sequencing (NGS). We identified significant HLA alleles (according to the conventional nomenclature), SNPs and haplotypes in the HLA-B, -C, -F, -DQA1, -DRB1, and -DRB5 genes associated with COVID-19 severity. Interestingly, these variants showed biological sex-related effects. Also, we identified specific haplotypes associated with COVID-19 severity that are shared by different conventional HLA alleles, indicated here as "super-haplotypes". These haplotypes had a biological sex-specific impact on disease severity and markedly increased the risk of severe COVID-19 compared to the conventional HLA alleles (odds ratio of up to 15). Our data suggest that the revision of the current HLA nomenclature may help to identify variants with a stronger effect on disease susceptibility and that association studies could benefit from the stratification of patients by biological sex. If replicated in other disease models, these findings could help to define the functional diversity in immune response between sexes, also based on the HLA system. Finally, due to the global pandemic's mortality rate, we hypothesize here that SARS-CoV-2 may have acted as a natural selection trigger, leading to a drift in HLA allelic frequencies in the general population.

ObjectivesThe aim of this work was to study characteristics, outcomes and predictors of all-cause death in inpatients with SARS-CoV-2 infection across the pandemic waves in one large teaching hospital in Italy to optimize disease management.MethodsAll patients with SARS-CoV-2 infection admitted to our center from March 2020 to June 2022 were included in this retrospective observational cohort study. Both descriptive and regression tree analyses were applied to identify factors influencing all-cause mortality.Results527 patients were included in the study (65.3% with moderate and 34.7% with severe COVID-19). Significant evolutions of patient characteristics were found, and mortality increased in the last wave with respect to the third wave notwithstanding vaccination. Regression tree analysis showed that in-patients with severe COVID-19 had the greatest mortality across all waves, especially the older adults, while prognosis depended on the pandemic waves in patients with moderate COVID-19: during the first wave, dyspnea was the main predictor, while chronic kidney disease emerged as determinant factor afterwards.ConclusionPatients with severe COVID-19, especially the older adults during all waves, as well as those with moderate COVID-19 and concomitant chronic kidney disease during the most recent waves require more attention for monitoring and care. Therefore, our study drives attention towards the importance of co-morbidities and their clinical impact in patients with COVID-19 admitted to hospital, indicating that the healthcare system should adapt to the evolving features of the epidemic.

IntroductionSexually transmitted diseases (STDs) are a major cause of long-term disability. Urethral discharge syndrome (UDS), abnormal vaginal discharge (AVD) and genital ulcer disease (GUD) are very common in low-income and middle-income countries (LMICs), where, due to lack of resources, these infections are managed according to a syndromic approach. Although microbiological diagnosis using nuclear acid amplification tests (NAAT) is already a standard to prescribe targeted treatments in industrialised countries, no randomised clinical trials have been conducted to evaluate clinical usefulness and acceptability of NAAT in comparison with syndromic approach in LMICs. The results of this study could inform diagnostic guidelines since they may suggest an update of the current recommendation if microbiological diagnosis using NAAT in the management of STD is demonstrated to be both useful and acceptable in an LMIC context.Methods and analysisThe primary objective of this randomised, open-label trial is to evaluate the clinical usefulness of a NAAT and its acceptability in comparison with a clinical syndromic approach and to explore whether this test could replace the syndromic approach in the management of STDs at a national referral hospital in Uganda. 220 patients presenting to the STD clinic at Mulago Hospital in Kampala, Uganda with AVD, UDS or GUD will be randomised to either standard of care (syndromic management) or NAAT-based treatment with a 1:1 ratio. All the patients will be asked to return after 2 or 3 weeks for a control visit. Primary outcome will be therapeutic appropriateness.Ethics and disseminationThis trial was approved by the Mulago Hospital Research and Ethical Committee (MHREC2023-97) and the Uganda National Council for Science and Technology (HS31000ES). Patients will give informed consent to participate before taking part in the study. Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form.Trial registration numberNCT05994495.

In the context of the evolving global health landscape shaped by the COVID-19 pandemic, tuberculosis (TB) is gaining renewed attention as a reemerging threat even in low-endemic countries. Immunological tests such as the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) are pivotal in identifying tuberculosis infection (TBI). However, their inability to distinguish between past and ongoing infection poses a diagnostic challenge, possibly leading to the unnecessary treatment of a significant portion of the population with potential side effects. This review delves into the concept of incipient tuberculosis (ITB), a dynamic, presymptomatic stage characterized by heightened Mycobacterium tuberculosis complex (MTC) metabolic activity and replication that result in minimal radiological changes, signifying a transitional state between TBI and TB. Key focus areas include epidemiological factors, underlying pathogenesis, imaging findings, and the ongoing challenges in the identification of individuals with ITB through the development of new biomarkers and the use of whole-genome sequencing-based analyses to implement early treatment strategies.