HIV screening of migrants in the autonomous Province of Trento (north of Italy).

Abstract: Migrants have accounted for more than 40% of new HIV diagnoses in Europe in 2022. Among the population of asylum seekers currently present in the Trento Province, screening for HIV infection is poorly carried out for various reasons. Here we report our experience about screening for HIV infection in asylum seekers present in that area using rapid self HIV-testing.

The diagnostic yield of the Meares & Stamey test can be significantly improved by symptom-based patient selection and the experience of the test performer.

BACKGROUND: Even if Meares-Stamey 4-glass (M&S) test is regarded a decisive tool for diagnosing prostatitis its use is only rarely performed in everyday clinical practice. Here, we analyze if the diagnostic yield of the M&S test could be improved by a pre-test categorization of patients due to undergo a M&S test. METHODS: All clinical and microbiological data of patients who underwent M&S test in two urological centers from January 2004 to December 2021 were analyzed in this retrospective cohort study. One center has a dedicated staff member for the study of prostatitis (Cohort I), while the other center is a general urological unit (Cohort II). All patients were divided into 3 groups on the basis of the assembled data: patients with symptoms related to prostatitis only (Group I), patients with symptoms related to both prostatitis and BPH (Group II), patients with symptoms related to BPH only (Group III). The rates of positive microbiological results in each group were compared. RESULTS: In the whole period, 9347 patients were analyzed and categorized as follows: Group I, 1884; Group II, 5151; Group III, 2312. Three-thousand and eight-hundred twenty-three patients showed positive culture results (40.9%). The most common isolated species was Escherichia coli (49.7%), followed by Enteroccus spp. (31.8%). The rates of positive M&S tests in the different symptom groups were: Group I, 1532 (81.4%); Group II, 1494 (29.0%); Group III, 797 (34.4%). The overall rate of positive M&S tests in each urology center showed that the center with a staff member who is dedicated to prostatitis studies (Cohort I) had a significantly higher rate of positive M&S tests than the general urological department (Cohort II) (64.3% vs 31.4%; p < 0.001). CONCLUSIONS: Symptom-based patient selection and dedicated staff members will increase the diagnostic yield of the M&S test and reduce the number of unnecessary tests.

Short Cycle, Intermittent Therapy: A Valuable Option in Selected, Virologically Suppressed People Living with HIV.

The use of long-acting antiretroviral regimens will not be suitable for all people living with HIV for various reasons (previous virological failure with drugs of the same class, side effects, logistic difficulties, and costs). We think that short-cycle therapies could represent a feasible and valuable option for antiretroviral treatment optimization in selected individuals. So here we review clinical evidence about efficacy of short-cycle therapy in suppressed HIV-infected patients.

Antibiotic Resistance Patterns Among Uropathogens in Female Outpatients Affected by Uncomplicated Cystitis: Focus on Fosfomycin Trometamol.

OBJECTIVES: To report the resistance rate against fosfomycin trometamol among outpatient women with symptoms related to urinary tract infections over a 6-year period in a multicentre, cross-sectional study. METHODS: Urinary samples were collected from three high-volume laboratories from January 2015 to December 2020. The pattern of resistance to fosfomycin was analysed by using the Vitek II automated system. RESULTS: A total of 7289 urinary samples were collected and 8321 strains were analysed during the study period. The most commonly isolated uropathogen was Escherichia coli (n = 6583, 79.1%). The mean resistance rate against fosfomycin was 9.7% (range 7.1-11.3). No statistically significant difference was found between the three laboratories (P = 0.53). There was no significant increase in resistance rate during the study period. The mean resistance rate against fosfomycin was higher among extended-spectrum ß-lactamase (ESBL)-producing bacteria when compared with non-ESBL-producing strains (10.8% vs. 7.9%; P < 0.001). CONCLUSION: Uropathogens isolated from women affected by cystitis remained highly susceptible to fosfomycin. These findings confirm recommendations in international guidelines that advocate fosfomycin trometamol for empirical treatment of uncomplicated cystitis in women.

Acceptability of Switching to Long-Acting Cabotegravir and Rilpivirine Among People Living with HIV on Dolutegravir/Rilpivirine Combination: A Single-Center Experience.

The availability of long-acting cabotegravir and rilpivirine injection combination requires some changes in service delivery of outpatient HIV clinics; it is therefore important for clinicians to know the potential number of people living with HIV (PLWH) who are interested in a long-acting antiretroviral treatment. We aimed to determine in an outpatient clinic the number of PLWH, on dolutegravir/rilpivirine, accepting a switch to an injectable long-acting antiretroviral treatment, and the reasons underlying this choice. In our single-center study, in this subset of HIV-infected patients, the main cause for refusal of a long-acting injectable regimen was the need for the administration to be done in hospital, as required in Italy, suggesting that current regulations about this aspect must be changed.

Real-life comparison of mortality in patients with SARS-CoV-2 infection at risk for clinical progression treated with molnupiravir or nirmatrelvir plus ritonavir during the Omicron era in Italy: a nationwide, cohort study.

Background: Comparative data on mortality in COVID-19 patients treated with molnupiravir or with nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause mortality in community-dwelling COVID-19 patients treated with these drugs during the Omicron era. Methods: Data collected in the nationwide, population-based, cohort of patients registered in the database of the Italian Medicines Agency (AIFA) were used. To increase completeness of the recorded deaths and date correctness, a cross-check with the National Death Registry provided by the Ministry of the Interior was performed. We included in this study all patients infected by SARS-CoV-2 treated within 5 days after the test date and symptom onset between February 8 and April 30, 2022. All-cause mortalities by day 28 were compared between the two treatment groups after balancing for baseline characteristics using weights obtained from a gradient boosting machine algorithm. Findings: In the considered timeframe, 17,977 patients treated with molnupiravir and 11,576 patients with nirmatrelvir plus ritonavir were included in the analysis. Most patients (25,617/29,553 = 86.7%) received a full vaccine course including the booster dose. A higher crude incidence rate of all-cause mortality was found among molnupiravir users (51.83 per 100,000 person-days), compared to nirmatrelvir plus ritonavir users (22.29 per 100,000 person-days). However, molnupiravir-treated patients were older than those treated with nirmatrelvir plus ritonavir and differences between the two populations were found as far as types of co-morbidities were concerned. For this reason, we compared the weight-adjusted cumulative incidences using the Aalen estimator and found that the adjusted cumulative incidence rates were 1.23% (95% CI 1.07%-1.38%) for molnupiravir-treated and 0.78% (95% CI 0.58%-0.98%) for nirmatrelvir plus ritonavir-treated patients (adjusted log rank p = 0.0002). Moreover, the weight-adjusted mixed-effect Cox model including Italian regions and NHS centers as random effects and treatment as the only covariate confirmed a significant reduced risk of death in patients treated with nirmatrelvir plus ritonavir. Lastly, a significant reduction in the risk of death associated with nirmatrelvir plus ritonavir was confirmed in patient subgroups, such as in females, fully vaccinated patients, those treated within day 2 since symptom onset and patients without (haemato)-oncological diseases. Interpretation: Early initiation of nirmatrelvir plus ritonavir was associated for the first time with a significantly reduced risk of all-cause mortality by day 28 compared to molnupiravir, both in the overall population and in patient subgroups, including those fully vaccinated with the booster dose. Funding: This study did not receive funding.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Features of Mpox infection: The analysis of the data submitted to the ID-IRI network.

Background: Mpox is a rare zoonotic disease caused by the Mpox virus. On May 21, 2022, WHO announced the emergence of confirmed Mpox cases in countries outside the endemic areas in Central and West Africa. Methods: This multicentre study was performed through the Infectious Diseases International Research Initiative network. Nineteen collaborating centres in 16 countries participated in the study. Consecutive cases with positive Mpoxv-DNA results by the polymerase chain reaction test were included in the study. Results: The mean age of 647 patients included in the study was 34.5.98.6% of cases were males, 95.3% were homosexual-bisexual, and 92.2% had a history of sexual contact. History of smallpox vaccination was present in 3.4% of cases. The median incubation period was 7.0 days. The most common symptoms and signs were rashes in 99.5%, lymphadenopathy in 65.1%, and fever in 54.9%. HIV infection was present in 93.8% of cases, and 17.8% were followed up in the hospital for further treatment. In the two weeks before the rash, prodromal symptoms occurred in 52.8% of cases. The incubation period was 3.5 days shorter in HIV-infected Mpox cases with CD4 count <200/µL, we disclosed the presence of lymphadenopathy, a characteristic finding for Mpox, accompanied the disease to a lesser extent in cases with smallpox vaccination. Conclusions: Mpox disseminates globally, not just in the endemic areas. Knowledge of clinical features, disease transmission kinetics, and rapid and effective implementation of public health measures are paramount, as reflected by our findings in this study.

Successful treatment of persistent SARS-CoV-2 infection with nirmatrelvir/ritonavir plus sotrovimab in four immunocompromised patients.

Immunocompromised patients with leukemia/lymphoma often have a suboptimal response to vaccination against SARS-CoV-2 and, if infected, can develop a persistent infection.SARS-CoV-2 PCR was performed on nasopharingeal swabs and serum IgG anti-SARS-CoV-2 trimeric spike glycoprotein antibodies were measured during persistence of infection. Treatment with a combination of nirmatrelvir/ritonavir plus sotrovimab led to viral clearance in three patients with leukaemia or lymphoma with persistent SARS-CoV-2 and negative SARS-CoV-2 antibody tests. No standardized treatments for persistent infection with SARS-CoV-2 infection are available. We have reported the viral clearance in two immunocompromised patients treated with antiviral drug nirmatrelvir/ritonavir and monoclonal antibody sotrovimab. We suggest that this strategy should be tested in clinical trials to find the right strategy for a clinical problem with public health implications to SARS-CoV-2 evolution and immune escape in these sub-set of patients.

Clinical efficacy of different monoclonal antibody regimens among non-hospitalised patients with mild to moderate COVID-19 at high risk for disease progression: a prospective cohort study.

This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700-1400 mg) or casirivimab-imdevimab (1200-1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30-0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03-0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants.

[Klebsiella pneumoniae resistente ai carbapenemici: prevalenza delle infezione ematiche prima e dopo la pandemia da SARS-CoV-2 in un ospedale di livello terziario del Nord-Est italiano.] / Klebsiella pneumoniae resistant to carbapenems: bloodstream infection prevalence before and during the SARS-CoV-2 pandemic in a tertiary level, North-Eastern Italian Hospital.

Riassunto. La pandemia da covid-19 ha comportato un incremento dell'uso degli antibiotici e dell'antibiotico-resistenza negli ospedali, sia negli Stati Uniti che in Europa, causando un aumento della morbilità e della mortalità nei pazienti ospedalizzati per la covid-19. Come in altri ospedali anche noi abbiamo documentato un incremento delle colonizzazioni e infezioni da germi multiresistenti. In questo studio siamo andati a valutare, nel nostro ospedale, come è cambiata la prevalenza delle infezioni ematiche da Klebsiella pneumoniae resistente ai carbapenemici nel periodo 2019-primo quadrimestre del 2021 (prima e durante la diffusione della pandemia covid-19). I nostri dati documentano un incremento significativo delle infezioni ematiche da Klebsiella pneumoniae resistente ai carbapenemici e un incremento dell'uso e dei costi per ceftazidime/avibactam.

Short-cycle therapy in HIV-infected adults: rilpivirine combination 4 days on/3 days off therapy.

BACKGROUND: Short-cycle therapy (SCT) is the administration of ART for 4 or 5 consecutive days a week, followed by 3 or 2 days off therapy. Its benefits include improving patient satisfaction and reducing ART toxicity and costs. METHODS: In this observational study we included HIV-infected adults with a three-drug ART containing rilpivirine, a history of long-term virological suppression and no evidence of resistance to previous drug regimens. Patients switched to a SCT of 4 days on/3 days off and were followed for 48 weeks with regular check-ups. The primary outcome was virological suppression; secondary outcomes were changes in CD4+ cells and rilpivirine plasma concentration, the occurrence of adverse events and resistance in the case of failure, and patient satisfaction. RESULTS: At week 48 no virological failure was observed, with a virological suppression rate of 30/30 (100%). Three patients switched back to continuous therapy for other reasons, with an overall success rate of SCT of 30/33 (90.9%, 95% CI = 81.24% to 100%). The CD4+ mean value increased by +64 cells/mm3 (95% CI = -59 to +187 cells/mm3; P = 0.052). No adverse events were observed and the mean total score in the satisfaction questionnaire was 57.7/60 (96.22%). Rilpivirine plasma concentration was below the efficacy threshold in 71.3% of the samples, suggesting that the patients' characteristics, more than the drug's pharmacokinetics, played a role in maintaining virological suppression. CONCLUSIONS: SCT with rilpivirine-containing regimens could be an effective alternative to continuous therapy in selected HIV-infected patients with previous long-term virological suppression.

A 58-year-old man with B-cell chronic lymphocytic leukemia and multiple strokes.

A 58-year-old male with B-cell chronic lymphocytic leukemia presented with fever, chest pain, and acute-onset neurological deficits suggestive of multiple strokes (A). Brain autopsy revealed softening areas in the brain parenchyma (B, C) corresponding to extensive necrosis (D) caused by neuroinvasion by Aspergillus hyphae (E, F) necrosis (D) caused by neuroinvasion by Aspergillus hyphae (E, F).

Mini-review: Silico-tuberculosis.

Silicosis continues to be a serious health issue in many countries and its elimination by 2030 (a target set by WHO and the International Labour Organization in 1995) is virtually impossible. The risk to develop pulmonary tuberculosis for silicosis patients is higher than for non-silicosis people, and there is also an increased risk of both pulmonary and extrapulmonary tuberculosis in individuals exposed to silica. HIV coinfection adds further to the risk, and in some countries, such as South Africa, miners living with HIV are a considerable number. The diagnosis of active tuberculosis superimposed on silicosis is often problematic, especially in initial phases, and chest X-ray and smear examination are particularly important for the diagnosis of pulmonary tuberculosis. Treatment is difficult; directly observed therapy is recommended, a duration of at least eight months is probably needed, drug reactions are frequent and the risk of relapse higher than in non-silicosis patients. TB prevention in silicosis patients is essential and include active surveillance of the workers, periodic chest X-rays, tuberculin skin test or interferon-gamma releasing assay testing, and, importantly, adoption of measures to reduce the exposure to silica dust. Chemoprophylaxis is possible with different regimens and needs to be expanded around the world, but efficacy is unfortunately limited. Silico-tuberculosis is still a challenging health problem in many countries and deserves attention worldwide.