Introduction: Acute eosinophilic pneumonia (AEP) is a rare respiratory condition caused by eosinophil accumulation in the pulmonary tissue that can be related to drug administration. Daptomycin, an antibiotic active against gram-positive bacteria, is one of the leading causes of AEP among drugs. In order to raise awareness of this rare syndrome, in our work we have described a case of an 82-year-old male with Enterococcus faecalis endocarditis treated with daptomycin, who developed a daptomycin-induced AEP. We have performed a systematic review of the literature for all similar reported cases. Methods: The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To conduct the analysis, the terms “daptomycin AND eosinoph* AND pneum*” were entered into the databases Medline, CINAHL, and Embase on April 13, 2023. We considered all relevant records documenting AEP after daptomycin use. No restrictions in terms of year or language were made. A formal appraisal of observational studies was performed by Newcastle-Ottawa Scale. All results and data were reported by means of tables. Results: Our search identified 93 relevant records, published between 2007 and 2023. A total of 120 patients were considered. Patients who experienced AEP were mostly males (n = 88, 73.3%) with a mean age of 68.28 years (SD 11.54). Daptomycin was most frequently prescribed for osteoarticular infections (n = 75, 62.5%) and to treat gram-positive cocci infections. The most frequently isolated pathogen was methicillin-resistant Staphylococcus aureus. Daptomycin was mostly used with off-label indications (n = 89, 74%). Symptoms of AEP were usually reported after a mean of 21.75 days of treatment (range 3–84) and typically included fever, dyspnea, dry cough, and acute respiratory failure. Reported treatment strategies invariably included daptomycin withdrawal, respiratory support, and corticosteroid treatment. One hundred and sixteen patients fully recovered. A fatal outcome was described in 4 patients. Suggestive symptoms and imaging raised suspicion for AEP, confirmed with bronchoalveolar lavage in 57.5% of the cases. Discussion and Conclusions: Daptomycin-induced AEP is a rare but potentially fatal complication, mostly reported after long treatment with daptomycin. Clinicians should be aware of this syndrome, as it could be initially misdiagnosed for an acute infectious respiratory syndrome, resulting in a delay in its diagnosis and treatment. Furthermore, since the risk of developing AEP is increased by longer drug exposure, caution should be used when discussing the use of daptomycin in longer treatment regimens.

In this study, we provided a retrospective overview in order to better define SARS-CoV-2 variants circulating in Italy during the first two years of the pandemic, by characterizing the spike mutational profiles and their association with viral load (expressed as ct values), N-glycosylation pattern, hospitalization and vaccination. Next-generation sequencing (NGS) data were obtained from 607 individuals (among them, 298 vaccinated and/or 199 hospitalized). Different rates of hospitalization were observed over time and among variants of concern (VOCs), both in the overall population and in vaccinated individuals (Alpha: 40.7% and 31.3%, Beta: 0%, Gamma: 36.5% and 44.4%, Delta: 37.8% and 40.2% and Omicron: 11.2% and 7.1%, respectively, both p-values < 0.001). Approximately 32% of VOC-infected individuals showed at least one atypical major spike mutation (intra-prevalence > 90%), with a distribution differing among the strains (22.9% in Alpha, 14.3% in Beta, 41.8% in Gamma, 46.5% in Delta and 15.4% in Omicron, p-value < 0.001). Overall, significantly less atypical variability was observed in vaccinated individuals than unvaccinated individuals; nevertheless, vaccinated people who needed hospitalization showed an increase in atypical variability compared to vaccinated people that did not need hospitalization. Only 5/607 samples showed a different putative N-glycosylation pattern, four within the Delta VOC and one within the Omicron BA.2.52 sublineage. Interestingly, atypical minor mutations (intra-prevalence < 20%) were associated with higher Ct values and a longer duration of infection. Our study reports updated information on the temporal circulation of SARS-CoV-2 variants circulating in Central Italy and their association with hospitalization and vaccination. The results underline how SARS-CoV-2 has changed over time and how the vaccination strategy has contributed to reducing severity and hospitalization for this infection in Italy.

Background: Actinomyces turicensis is rarely responsible of clinically relevant infections in human. Infection is often misdiagnosed as malignancy, tuberculosis, or nocardiosis, therefore delaying the correct identification and treatment. Here we report a case of a 55-year-old immunocompetent adult with brain abscess caused by A. turicensis. A systematic review of A. turicensis infections was performed. Methods: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases MEDLINE, Embase, Web of Science, CINAHL, Clinicaltrials.gov and Canadian Agency for Drugs and Technology in Health (CADTH) were searched for all relevant literature. Results: Search identified 47 eligible records, for a total of 67 patients. A. turicensis infection was most frequently reported in the anogenital area (n = 21), causing acute bacterial skin and skin structure infections (ABSSSI) including Fournier’s gangrene (n = 12), pulmonary infections (n = 8), gynecological infections (n = 6), cervicofacial district infections (n = 5), intrabdominal or breast infections (n = 8), urinary tract infections (n = 3), vertebral column infections (n = 2) central nervous system infections (n = 2), endocarditis (n = 1). Infections were mostly presenting as abscesses (n = 36), with or without concomitant bacteremia (n = 7). Fever and local signs of inflammation were present in over 60% of the cases. Treatment usually involved surgical drainage followed by antibiotic therapy (n = 51). Antimicrobial treatments most frequently included amoxicillin (+clavulanate), ampicillin/sulbactam, metronidazole or cephalosporins. Eighty-nine percent of the patients underwent a full recovery. Two fatal cases were reported. Conclusions: To the best of our knowledge, we hereby present the first case of a brain abscess caused by A. turicensis and P. mirabilis. Brain involvement by A. turicensis is rare and may result from hematogenous spread or by dissemination of a contiguous infection. The infection might be difficult to diagnose and therefore treatment may be delayed. Nevertheless, the pathogen is often readily treatable. Diagnosis of actinomycosis is challenging and requires prompt microbiological identification. Surgical excision and drainage and antibiotic treatment usually allow for full recovery.

There are still conflicting data on the virological effects of the SARS-CoV-2 direct antivirals used in clinical practice, in spite of the documented clinical efficacy. The aim of this monocentric retrospective study was to compare virologic and laboratory data of patients admitted due to SARS-CoV-2 infection from March to December 2020 treated with either remdesivir (R), a protease inhibitor (lopinavir or darunavir/ritonavir (PI)) or no direct antiviral drugs (NT). Viral load variation was indirectly assessed through PCR cycle threshold (Ct) values on the nasopharyngeal swab, analyzing the results from swabs obtained at ward admission and 7 (±2) days later. Overall, 253 patients were included: patients in the R group were significantly older, more frequently males with a significantly higher percentage of severe COVID-19, requiring more often intensive care admission, compared to the other groups. Ct variation over time did not differ amongst the three treatment groups and did not seem to be influenced by corticosteroid use, even after normalization of the treatment groups for disease severity. Non-survivors had lower Ct on admission and showed a significantly slower viral clearance compared to survivors. CD4 T-lymphocytes absolute count assessed at ward admission correlated with a reduced Ct variation over time. In conclusion, viral clearance appears to be slower in COVID-19 non-survivors, while it seems not to be influenced by the antiviral treatment received.

Co-infections during COVID-19 may worsen patients’ outcomes. This study reports the results of a screening assessing the presence of co-infections among patients hospitalized for SARS-CoV-2 infection in the Infectious Diseases-Ward of the Policlinico Tor Vergata Hospital, Rome, Italy, from 1 January to 31 December 2021. Data on hepatitis B and C virus, urinary antigens for legionella pneumophila and streptococcus pneumoniae, pharyngeal swab for respiratory viruses, QuantiFERON^®-TB Gold Plus assay (QFT-P), blood cultures and pre-hospitalization antibiotic prescription were recorded. A total of 482 patients were included, 61% males, median age of 65 years (IQR 52–77), median Charlson comorbidity index of 4 (IQR 2–5). The mortality rate was 12.4%; 366 patients needed oxygen supply. In total, 151 patients (31.3%) received home antibiotics without any association with the outcome. No significant association between mortality and the positivity of viral hepatitis markers was found. Out of 442 patients, 125 had an indeterminate QFT-P, associated with increased mortality. SARS-CoV-2 was the only respiratory virus detected among 389 pharyngeal swabs; 15/428 patients were positive for S. pneumoniae; none for L. pneumophila. In total, 237 blood cultures were drawn within 48 h from hospital admission: 28 were positive and associated with increased mortality. In our cohort, bacterial and viral co-infections in COVID-19 hospitalized patients were rare and not associated with higher mortality.

Lymphopenia has been consistently reported as associated with severe coronavirus disease 2019 (COVID-19). Several studies have described a profound decline in all T-cell subtypes in hospitalized patients with severe and critical COVID-19. The aim of this study was to assess the role of T-lymphocyte subset absolute counts measured at ward admission in predicting 30-day mortality in COVID-19 hospitalized patients, validating a new prognostic score, the T-Lymphocyte Subset Index (TLSI, range 0–2), based on the number of T-cell subset (CD4+ and CD8+) absolute counts that are below prespecified cutoffs. These cutoff values derive from a previously published work of our research group at Policlinico Tor Vergata, Rome, Italy: CD3+CD4+ < 369 cells/μL, CD3+CD8+ < 194 cells/μL. In the present single-center retrospective study, T-cell subsets were assessed on admission to the infectious diseases ward. Statistical analysis was performed using JASP (Version 0.16.2. JASP Team, 2022, Amsterdam, The Netherlands) and Prism8 (version 8.2.1. GraphPad Software, San Diego, CA, USA). Clinical and laboratory parameters of 296 adult patients hospitalized because of COVID-19 were analyzed. The overall mortality rate was 22.3% (66/296). Survivors (S) had a statistically significant lower TLSI score compared to non-survivors (NS) (p < 0.001). Patients with increasing TLSI scores had proportionally higher rates of 30-day mortality (p < 0.0001). In the multivariable logistic analysis, the TLSI was an independent predictor of in-hospital 30-day mortality (OR: 1.893, p = 0.003). Survival analysis showed that patients with a TLSI > 0 had an increased risk of death compared to patients with a TLSI = 0 (hazard ratio: 2.83, p < 0.0001). The TLSI was confirmed as an early and independent predictor of COVID-19 in-hospital 30-day mortality.