Francesco Barchiesi

Background: Despite suppressive antiretroviral therapy (ART), HIV-1 persists in infected cells as integrated proviral DNA and as more labile unintegrated DNA forms (uDNA). The presence of uDNA has been proposed as a surrogate marker of recent infection events occurring below the detection limits of plasma HIV-1 RNA assays. The aim of this study was to evaluate the performance of an assay for the quantification of uDNA in peripheral whole blood of people with HIV (PWH), with the intent of identifying individuals with no evidence of recent infection events, defined as undetectable uDNA, and to characterize associated clinical and immunological factors. Methods: Total and unintegrated HIV-1 DNA were quantified by real-time PCR in whole blood samples from 87 chronically treated PWH. Samples were derived from a real-world, retrospective cohort and reflected the antiretroviral regimens actually received by patients over time. Clinical, virological, and immunological parameters were analyzed in relation to uDNA detectability. Results: Overall, uDNA was quantifiable in 11/87 (13%) samples, detectable below the assay quantification limit in 52/87 (60%), and undetectable (target not detected) in 24/87 (28%). Undetectable uDNA was associated with higher CD4⁺ T-cell nadir, higher current CD4⁺ T-cell counts, and lower total HIV-1 DNA levels. In multivariable analysis, CD4⁺ T-cell nadir was the only factor independently associated with uDNA undetectability ( p = 0.001). Antiretroviral regimen characteristics were not independently associated with uDNA detectability. Conclusions: A substantial proportion of chronically treated PWH exhibited undetectable uDNA in peripheral blood. The uDNA measurement provides complementary information to plasma HIV-1 RNA and CD4⁺ T-cell counts and may help identify individuals with no evidence of recent infection events and higher immunological fitness. These findings support the potential utility of uDNA quantification as a biomarker of HIV-1 reservoir dynamics in real-world clinical settings.

Candidemia is an alarming problem in critically ill patients including those admitted in Internal Medicine Wards (IMWs). Here, we analyzed all cases of candidemia in adult patients hospitalized over nine years (2010–2018) in IMWs of a 980-bedded University Hospital of Ancona, Italy. During the study period, 218/505 (43%) episodes of candidemia occurred in IMWs patients. The cumulative incidence was 2.5/1000 hospital admission and increased significantly over time (p = 0.013). Patients were predominantly male, with a median age of 68 years. Cardiovascular diseases and solid tumors were the most frequent comorbidities. Candida albicans accounted for 51% of the cases, followed by C. parapsilosis (25%), C. tropicalis (9%) and C. glabrata (7%). Thirty-day mortality was 28% and did not increased significantly over time. By multivariate logistic regression analysis, the presence of neutropenia (OR 7.247 [CI95% 1,368–38,400; p = 0.020]), pneumonia (OR 2.323 [CI95% 1,105–4,884; p = 0.026]), and being infected with C. albicans (OR 2.642 [95% CI 1,223–5,708; p = 0.013) emerged as independent predictors of mortality. The type of antifungal therapy did not influence the outcome. Overall, these data indicate that patients admitted to IMWs are increasingly at higher risk of developing candidemia. Mortality rate remains high and significantly associated with both microbiologic- and host-related factors.

The effect of the COVID-19 pandemic on antibiotic resistance diffusion in healthcare settings has not been fully investigated. In this study we evaluated the prevalence of antibiotic resistance among opportunistic pathogens isolated from patients with COVID-19 under mechanical ventilation. An observational, retrospective, analysis was performed on confirmed cases of COVID-19 patients who were admitted to the ICU department of San Salvatore Hospital in Pesaro, Italy, from 1 February 2021 to 31 May 2021. We considered all consecutive patients aged ≥ 18, under mechanical ventilation for longer than 24 h. Eighty-nine patients, 66 (74.1%) men and 23 (25.9%) women, with a median age of 67.1 years, were recruited. Sixty-eight patients (76.4%) had at least one infection, and 11 patients (12.3%) were colonized, while in the remaining 10 patients (11.2%) neither colonization nor infection occurred. In total, 173 microorganisms were isolated. There were 73 isolates (42.2%) causing bacterial or fungal infections while the remaining 100 isolates (57.8%) were colonizers. Among Gram-negative bacteria, E. coli, A. baumannii and K. pneumoniae were the most common species. Among Gram-positive bacteria, S. aureus and E. faecalis were the most common species. Overall, there were 58/105 (55.2%) and 22/59 (37.2%) MDR isolates among Gram-negative and Gram-positive bacteria, respectively. The prevalence of an MDR microorganism was significantly higher in those patients who had been exposed to empiric antibiotic treatment before ICU admission. In conclusion, we found a high prevalence of antibiotic resistance among opportunistic pathogens isolated from patients with COVID-19 under mechanical ventilation.

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations against dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies and 31 articles referring to case reports or clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts or essential oils, calcineurin inhibitors, peptides, disinfectant agents, and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections, an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e., terbinafine, griseofulvin, or azole—mainly itraconazole) plus a topical medication (i.e., azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful to accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available so far, it is desirable to continue the research in this field.

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations in dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies, and 31 articles referring to case reports/clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts/essential oils, calcineurin inhibitors, peptides, disinfectant agents and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e.: azole [mainly itraconazole], terbinafine or griseofulvin) plus a topical medication (i.e.: azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful in accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available as far, it is desirable to continue the research in this field.

Purpose: Candidemia is an alarming problem in critically ill patients including those admitted in intensive care units (ICUs). We aimed to describe the clinical and microbiological characteristics of bloodstream infections (BSIs) due toCandidaspp. in patients admitted to ICUs of an italian tertiary referral university hospital over nine years.Methods: A retrospective observational study of all cases of candidemia in adult patients was carried out from January 1, 2010 to December 31, 2018 at a 980-bedded University Hospital in Ancona, Italy, counting five ICUs. The incidence, demographics, clinical and microbiologic characteristics, therapeutic approaches and outcomes of ICU-patients with candidemia were collected. Non-ICU patients with candidemia hospitalized during the same time period were considered for comparison purposes. Early (7 days from the occurrence of the episode ofCandidaBSI) and late (30 days) mortality rates were calculated.Results: During the study period, 188/505 (36%) episodes of candidemia occurred in ICU patients. Cumulative incidence was 9.9/1000 ICU admission and it showed to be stable over time.Candida albicansaccounted for 52% of the cases, followed byC.parapsilosis(24%), andC.glabrata(14%). There was not a significant difference in species distribution between ICU and non-ICU patients. With the exception of isolates ofC.tropicaliswhich showed to be fluconazole resistant in 25% of the cases, resistance to antifungals was not of concern in our patients. Early and late mortality rates, were 19% and 41% respectively, the latter being significantly higher than that observed in non-ICU patients. At multivariate analysis, factors associated with increased risk of death were septic shock, acute kidney failure, pulmonary embolism and lack of antifungal therapy. The type of antifungal therapy did not influence the outcome. Mortality did not increased significantly over time.Conclusion: Neither cumulative incidence nor crude mortality of candidemia in ICU patients increased over time at our institution. However, mortality rate remained high and significantly associated with specific host-related factors in the majority of cases.

Candidemia is an alarming problem in critically ill patients including those admitted in Internal Medicine Wards (IMWs). Here, we analyzed all cases of candidemia in adult patients hospitalized over nine years (2010–2018) in IMWs of a 980-bedded University Hospital of Ancona, Italy. During the study period, 218/505 (43%) episodes of candidemia occurred in IMWs patients. The cumulative incidence was 2.5/1000 hospital admission and increased significantly over time (p = 0.013). Patients were predominantly male, with a median age of 68 years. Cardiovascular diseases and solid tumors were the most frequent comorbidities. Candida albicans accounted for 51% of the cases, followed by C. parapsilosis (25%), C. tropicalis (9%) and C. glabrata (7%). Thirty-day mortality was 28% and did not increased significantly over time. By multivariate logistic regression analysis, the presence of neutropenia (OR 7.247 [CI95% 1,368 − 38,400; p = 0.020]), pneumonia (OR 2.323 [CI95% 1,105-4,884; p = 0.026]), and being infected with C. albicans (OR 2.642 [95% CI 1,223-5,708; p = 0.013) emerged as independent predictors of mortality. The type of antifungal therapy did not influence the outcome. Overall, these data indicate that patients admitted to IMWs are increasingly at higher risk of developing candidemia. Mortality rate remains high and significantly associated with both microbiologic- and host-related factors.

Background: The outbreak of COVID-19 has rapidly spread to Italy, including Pesaro-Urbino province. Data on young to middle age adults with COVID-19 are lacking. We report the characteristics, management and health-related quality of life (HRQoL) in patients with COVID-19 aging ≤50 years. Methods: A retrospective analysis was performed in all patients ≤50 years with a confirmed diagnosis of COVID-19 admitted to Emergency department (ED) of San Salvatore Hospital in Pesaro from February 28th to April 8th, 2020. Data were collected from electronical medical records. HRQoL was investigated after 1 month from hospital discharge using the SF-36 questionnaire. Outcomes were evaluated between hospitalized and not hospitalized patients. Results: Among 673 patients admitted to the ED and diagnosed with COVID-19, 104 (15%) were ≤ 50 years old: 74% were discharged at home within 48 h, 26% were hospitalized. Fever occurred in 90% of the cases followed by cough (56%) and dyspnoea (34%). The most frequent coexisting conditions were hypertension (11%), thyroid dysfunction (8%) and neurological and/or mental disorders [NMDs] (6%). Mean BMI was 27. Hypokalaemia and NMDs were significantly more common in patients who underwent mechanical ventilation. Regardless of hospitalization, there was an impairment in both the physical and mental functioning. Conclusions: Overweight and hypertension are frequent conditions in young to middle age adults with COVID-19. Hypokalaemia and NMDs are commonly associated with progressive disease. A significant impact on HRQoL in the early stage of post-discharge is common in this population.

Purpose: Candidemia is an alarming problem in critically ill patients including those admitted in intensive care units (ICUs). We aimed to describe the clinical and microbiological characteristics of bloodstream infections (BSIs) due to Candida spp. in patients admitted to ICUs of an italian tertiary referral university hospital over nine years. Methods: A retrospective observational study of all cases of candidemia in adult patients was carried out from January 1, 2010 to December 31, 2018 at a 980-bedded University Hospital in Ancona, Italy, counting five ICUs. The incidence, demographics, clinical and microbiologic characteristics, therapeutic approaches and outcomes of ICU-patients with candidemia were collected. Early (7 days from the occurrence of the episode of Candida BSI) and late (30 days) mortality rates were calculated. Results: During the study period, 188/505 (36%) episodes of candidemia occurred in ICU patients. Incidence rate was 9.9/1000 ICU admission and it showed to be stable over time. Candida albicans accounted for 52% of the cases, followed by C. parapsilosis (24%), and C. glabrata (14%). With the exception of isolates of C. tropicalis which showed to be fluconazole resistant in 25% of the cases, resistance to antifungals was not of concern in our patients. Early and late mortality rates were 19% and 41%, respectively and did not increased significantly over time. Independent risk factors for higher mortality were septic shock, acute kidney failure, pulmonary embolism and lack of antifungal therapy. The type of antifungal therapy did not influence the outcome. Conclusion: Neither incidence rate nor crude mortality of candidemia in ICU patients increased over time at our institution. However, mortality rate remained high and significantly associated with specific host-related factors.