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Background: People with HIV (PWH) are at increased risk of atherosclerotic cardiovascular disease (ASCVD). Lowering low-density lipoprotein cholesterol (LDL-C) is central of cardiovascular disease prevention. The aim of this study was to assess the prevalence, treatment, and control of high LDL-C levels as assessed on the basis of the ASCVD risk profiles indicated by European Society of Cardiology (ESC) guidelines of a cohort of PWH in order to evaluate the state of LDL-C management in current clinical practice., Methods: We retrospectively assessed the prevalence, treatment, and control of high LDL-C levels in a cohort of PWH aged ≥40 years who accessed our HIV outpatient clinic between 1 March 2022 and 31 March 2023. Their 10-year ASCVD risk was calculated on the basis of their age and co-morbidities as recommended by guidelines. High LDL-C levels were defined as those above the "step two" target of their specific ASCVD risk category., Results: Among the 1404 assessed PWH, who were prevalently male (74.5 %) and Caucasian (85.6 %), and had a median age of 56 years (interquartile range [IQR] 49-61), 295 (21 %) were at very high risk (VHR), 634 (45.2 %) at high-risk (HR), and 348 (24.8 %) not at HR. The overall median LDL-C level was 116 mg/dL (IQR 96-141). Five hundred and sixteen (37 %) were undergoing lipid lowering treatment (LLT), and 650 (46.3 %) failed to achieve any step of their target LDL-C levels., Conclusions: Despite the high prevalence of PWH at VHR/HR for ASCVD, LDL-C levels were poorly controlled and LLT was greatly under used., Competing Interests: Declaration of competing interest AG has received consultancy fees and speakers' honoraria from ViiV, Gilead, Janssen, MSD and Mylan, outside the present work. CG has received personal fees from MSD, ViiV, Gilead, and Janssen Cilag, outside the present work. SA has received support for research activities from Pfizer, ViiV, Gilead and Merck Sharp & Dome, outside the present work. APM has received personal fees for participating in committees of studies supported by Bayer, Novartis, Sanofi, and Astra Zeneca, outside the present work. GC, BC, LO, SC, SL, AP, SP, MLC, MB, GC, and ALR have nothing to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: The diagnosis and management of malaria in non-endemic countries presents a continuing challenge. Plasmodium falciparum, which is capable of rapidly inducing severe and life-threatening multiorgan disease, is the species most frequently diagnosed in Europe and North America., Objectives: To summarise the more relevant diagnostic findings and clinical features of malaria observed in non-endemic settings and to provide an update of the key management decision points using three illustrative clinical scenarios of uncomplicated and severe malaria., Sources: The discussion is based on a relevant literature search spanning the last 20 years. Recommendations are based on available clinical guidelines including those of the WHO, observational studies conducted in non-endemic settings, and, when available, extrapolation from randomised studies from malaria-endemic settings., Content: The following topics are covered: diagnosis, including the use of molecular biology; clinical characteristics; management with a specific focus on complicated (severe) and uncomplicated malaria; and areas of resistance to available antimalarial drugs., Implications: Malaria imported to non-endemic settings, especially P. falciparum malaria, is sometimes initially overlooked and the delayed diagnosis is responsible for every year of preventable deaths. This review aims to raise awareness of malaria outside endemic countries and to provide clinicians with a practical guide for efficient diagnosis and targeted therapy for the different species involved., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: We compared the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) and dolutegravir plus lamivudine (DTG + 3TC) in our cohort of treatment-naive people with HIV (PWH)., Methods: In a multicentre cohort of treatment-naive PWH starting a first-line regimen with either dolutegravir plus lamivudine or BIC/FTC/TAF, Kaplan-Meier survival analysis was used to estimate time to virological failure (VF) and time to treatment discontinuation (TD), whereas Cox regression was used to evaluate predictors of VF and TD. Changes in CD4+ cell count were assessed via non-parametric tests, and linear regression analyses were performed to explore predictors of CD4+ cell count changes., Results: One hundred and seventy individuals were included: 66 started dolutegravir plus lamivudine (DTG group) and 104 started BIC/FTC/TAF (BIC group). During follow-up, we observed two VFs in the DTG group [1.7 per 100 person-years of follow-up (PYFU)] and two in the BIC group (1.7 per 100 PYFU). Estimated probability of remaining free from VF at Week 144 was 95.9% in the DTG group and 95.2% in the BIC group (log-rank P = 0.955). Four TDs were observed in the DTG group (3.4 per 100 PYFU) and 21 in the BIC group (17.6 per 100 PYFU). Estimated probability of maintaining the study regimen at Week 144 was 90.3% in the DTG group and 70.0% in the BIC group; individuals in the BIC group had a higher probability of TD (log-rank P = 0.003). In both groups, the CD4+ count improved significantly during follow-up., Conclusions: Our study shows that both strategies are effective and safe, with few VFs and TDs due to tolerability issues., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Effective treatments for COVID-19 are needed to mitigate disease progression and reduce the burden on healthcare systems. This study investigates the impact of early treatments on SARS-CoV-2 viral shedding duration among high-risk individuals with mild symptoms., Methods: A single-center, retrospective observational study was conducted at Luigi Sacco Hospital in Milan from December 2021 to March 2023. Hospitalized and nonhospitalized adults with a confirmed SARS-CoV-2 infection and at high-risk of disease progression were enrolled. Unadjusted and adjusted negative binomial regression models and a Random Forest regression model were performed before and after matching subjects based on their propensity of being treated or not., Results: Results from 518 subjects (428 treated and 90 untreated) revealed a significant reduction in SARS-CoV-2 viral shedding duration among those who received early treatment compared to untreated individuals. Propensity score matching and multivariable regression analyses confirmed this finding. Early treatment significantly reduced the risk of COVID-19-related hospitalization and pneumonia development. Subgroup analysis identified COPD as a potential factor influencing effectiveness of early treatments., Conclusions: Early treatments play a crucial role in reducing SARS-CoV-2 viral shedding and preventing disease progression among high-risk individuals. Shorter viral shedding duration also contributes to improved healthcare resource utilization and infection control measures., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Terminology in schistosomiasis is not harmonised, generating misunderstanding in data interpretation and clinical descriptions. This study aimed to achieve consensus on definitions of clinical aspects of schistosomiasis in migrants and returning travellers. We applied the Delphi method. Experts from institutions affiliated with GeoSentinel and TropNet, identified through clinical and scientific criteria, were invited to participate. Five external reviewers revised and pilot-tested the statements. Statements focusing on the definitions of acute or chronic; possible, probable, or confirmed; active; and complicated schistosomiasis were managed through REDCap and replies managed in a blinded manner. Round 1 mapped the definitions used by experts; subsequent rounds were done to reach consensus, or quantify disagreement, on the proposed statements. Data were analysed with percentages, medians, and IQRs of a 5-point Likert scale. The study was terminated on the basis of consensus or stability-related and time-related criteria. 28 clinicians and scientists met the criteria for experts. 25 (89%) of 28 experts replied to Round 1, 18 (64%) of 28 to Round 2, 19 (68%) of 28 to Round 3, and 21 (75%) of 28 to at least two rounds. High-level consensus (79-100% agreement and IQRs ≤1) was reached for all definitions. Consensus definitions will foster harmonised scientific and clinical communication and support future research and development of management guidelines for schistosomiasis., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We present a challenging case of a patient admitted to an intensive care unit with influenza-associated pulmonary aspergillosis (IAPA). The clinical course was characterised by refractory fungal pneumonia and tracheobronchitis, suspected drug-induced liver injury due to triazole antifungals, and secondary bacterial infections with multidrug-resistant microorganisms, resulting in a fatal outcome despite the optimisation of antifungal treatment through therapeutic drug monitoring. This case underscores the complexity that clinicians face in managing critically ill patients with invasive fungal infections.

Background: Antiretroviral drug combinations affect dolutegravir trough concentrations. Here, the authors focused on dolutegravir plus booster darunavir antiretroviral regimens to investigate the effect of the booster and/or timing of drug administration on dolutegravir and darunavir plasma trough concentrations., Methods: This retrospective observational study included consecutive people with HIV (PWH) receiving dolutegravir plus booster darunavir antiretroviral regimens for at least 3 months, with at least one assessment of dolutegravir and darunavir plasma trough concentrations., Results: A total of 200 drug therapeutic drug monitoring results from 116 PWH were included. Dolutegravir and darunavir trough concentrations ranged, respectively, from 70 to 3648 mcg/L and from 102 to 11,876 mcg/L. The antiretroviral drug combination associated with the highest dolutegravir trough concentration was dolutegravir plus darunavir/cobicistat, both once daily (1410 ± 788 mcg/L), whereas dolutegravir once daily plus darunavir/ritonavir twice daily had the lowest trough concentrations (686 ± 481 mcg/L). Doubling the dose of dolutegravir did not significantly increase drug trough concentrations compared with that of once-daily regimens. Instead, the highest darunavir trough concentrations were with ritonavir (2850 ± 1456 mcg/L, P < 0.05 versus cobicistat-based regimens). Doubling the drug dose resulted in a significant increase in the darunavir trough concentration (4445 ± 2926 mcg/L, P < 0.05)., Conclusions: Dolutegravir trough concentrations were significantly reduced in PWH receiving darunavir/ritonavir twice daily. This evidence should be carefully considered in clinical conditions requiring higher dolutegravir exposure, such as in the presence of drug-drug interactions with drugs known to reduce dolutegravir bioavailability or in highly experienced PWH., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Monkeypox virus (MPXV) infection confirmation needs reliable polymerase chain reaction (PCR) assays; in addition, viral clade attribution is a key factor in containment measures, considering a more severe syndrome in clade I and the possibility of simultaneous circulation. This study evaluates the performance of all-in-one STANDARD M10 MPX/OPX (SD BIOSENSOR, South Korea - M10). Frozen samples from 205 subjects were selected and stratified according to routine test results (RealStar® Orthopoxvirus PCR Kit 1.0, Altona DIAGNOTICS, Germany - RS; RS-1): in detail, 100 negative skin lesions (SL) and 200 positive samples at the variable stage of infection were analysed. Positive samples were retested with RS (RS-2). Positive and Negative Percent Agreements (PPA, NPA) were calculated. The median (IQR) C t values of RS and M10 (OPXV target) assays were highly similar. The PPA of M10 compared to RS-1 was 89.5% considering system interpretation, and 96.0% when the operator classified results as positive if any target was detected; NPA was 100%. Comparing the RS-2 run and M10, an overall concordance of 95.3% between assays was found; however, considering operator interpretation, M10 returned more positive results than RS-2. The occurrence of False-Negative results was likely associated with the influence of thawing on low viral concentration; no False-Positive tests were observed. All samples collected at the time of Mpox diagnosis were positive and M10 correctly attributed the clade (West-Africa/II). The M10 MPX/OPX assay demonstrated high reliability in confirming MPXV infection and clade attribution.

The association between human papillomavirus (HPV) and other sexually transmitted infections (STIs) in anal lesions still remains unclear. Aim of the study was to evaluate the prevalence of simultaneous infection of HPV and Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in individuals screened for HPV anal infection. A total of 507 anal samples were tested for both anal HPV and STIs: 16% resulted positive for one or more non-HPV STIs. Specifically, C. trachomatis, M. genitalium, and N. gonorrhoeae were detected in 8%, 5%, and 4% of cases, respectively. Two groups were considered, including a positive STI group and a negative STI group. The prevalence of HPV was similar in patients in both groups: high risk (HR)-HPV and low risk (LR)-HPV were 67% and 53% versus 62% (p = 0.361) and 54% (p = 0.864) of patients, respectively. However, HPV 16, 18, 35, 51, 59, and 69 were significantly more frequent in patients tested positive for other STIs versus HPV infection alone (p < 0.05). No significant differences between the two groups were observed in vaccination coverage, 28% versus 32% (p = 0.463), and HIV status, 86% versus 84% (p = 0.658). The study shows that the overall HPV status is not directly correlated to other STIs in the investigated population, except for certain HPV types, including HR-HPV 16, reinforcing the urge for a greater vaccination coverage., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Purpose: Candida auris, an emerging multidrug-resistant yeast, has been reported worldwide. In Italy, the first case was reported in 2019. We describe the first case of C. auris, imported from Greece, in Milan, using whole genome sequencing to characterise mutations associated with antifungal resistance., Case Presentation: On October 2022 an 80-year-old Italian man was hospitalised in Greece. In the absence of clinical improvement, the patient was transferred to our hospital, in Italy, where blood culture resulted positive for C. auris. Despite therapy, the patient died of septic shock. In a phylogenetic analysis the genome was assigned to Clade I with strains from Kenya, United Arab Emirates and India. D1/D2 region resulted identical to a Greek strain, as for many other strains from different World regions, highlighting the diffusion of this strain., Conclusion: Importation of C. auris from abroad has been previously described. We report the first case of C. auris imported into Italy from Greece, according to phylogenetic analysis. This case reinforces the need for monitoring critically ill hospitalised patients also for fungi and addresses the need for the standardisation of susceptibility testing and strategies for diagnosis and therapy., (© 2024. The Author(s).)

Staphylococcus aureus bacteraemia (SAB) is a life-threatening bloodstream infection. Improved adherence to quality-of-care indicators (QCIs) can significantly enhance patient outcomes. This quasi-experimental study evaluated the impact of a bundle of interventions on QCI adherence in adult patients with SAB. Additionally, a molecular rapid diagnostic test (mRDT) for S. aureus and methicillin resistance was introduced during weekdays. We compared pre-intervention (January-December 2022) and post-intervention (May 2023-April 2024) data on QCI adherence and time to appropriate treatment. A total of 56 and 40 SAB episodes were included in the pre- and post-intervention periods, respectively. Full QCI adherence significantly increased from 28.6% to 67.5% in the post-intervention period ( p < 0.001). The mRDT diagnosed SAB in eight cases (26.6%), but the time to achieve appropriate target therapy did not improve in the post-intervention period (54 h (IQR 30-74) vs. 72 h (IQR 51-83), p = 0.131). The thirty-day mortality rate was comparable between the two periods (17.9% vs. 12.5%, p = 0.476). This study demonstrates that a bundle of interventions can substantially improve adherence to SAB management QCIs.

In October, 2022, WHO published the first fungal priority pathogen list, which categorised 19 fungal entities into three priority groups (critical, high, and medium), for prioritisation of research efforts. The final ranking was determined via multiple criteria decision analysis, considering both research and development needs and perceived public health importance. In this Personal View, we discuss the positioning of the fungal pathogens, namely, Mucorales, Candida spp, Histoplasma spp, Coccidioides and Paracoccidioides spp, Fusarium spp, eumycetoma causative agents, Talaromyces marneffei, and Pneumocystis jirovecii, while expressing concerns about potential disparities between the WHO fungal priority pathogen list ranking and the actual disease burden associated with these pathogens. Finally, we propose a revised prioritisation list that also considers the regional disparities in the burden of fungal diseases., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The aim of this study was to assess the prevalence of inappropriate treatment among hospitalised patients affected by SARS-CoV-2 infection before hospital admission during the Omicron era. This single-centre, retrospective observational study included all the patients hospitalised because of SARS-CoV-2 infection during three periods characterised by the Italian prevalence of an Omicron variant of concern: (1) January-May 2022 (BA.1-BA.2), (2) June-October 2022 (BA.5), and (3) November 2022-March 2023 (BQ.1-XBB). Inappropriate treatment was defined as pre-hospitalisation exposure to antibiotics and/or steroids in the absence of a documented bacterial infection or the need for steroid treatment of an underlying medical condition. A total of 931 subjects were hospitalised: 394 in period 1, 334 in period 2, and 203 in period 3. Of the 157 patients undergoing inappropriate treatment (16.9%), 142 (15.3%) received antibiotics and 52 (5.6%) steroids. The proportion of inappropriately treated patients significantly decreased over time, from 23.1% in period 1 to 11.7% in period 2 and 13.3% in period 3 ( p < 0.001), and there was a parallel decrease in antibiotic ( p < 0.001) and steroid treatment ( p < 0.013). Only 13 subjects (1.4%) received early pre-hospitalisation treatment for SARS-CoV-2. A significant proportion of hospitalised COVID-19 patients were exposed to inappropriate treatment before hospital admission.

Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords "PrEP" or "Pre-Exposure Prophylaxis" and "HIV" or "PLWH" and "breakthrough" or "acute infection" or "primary infection". We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals.

In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive Streptococcus pneumoniae infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, p = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency.

Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020-2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37-0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72-84 IQR) vs. 67 years (55-78 IQR), p -value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p -value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02-1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events.

Background: Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam., Methods: We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality., Results: The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy., Conclusions: Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy., Competing Interests: Potential conflicts of interest. No reported conflicts of interest, (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment., Methods: Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated., Results: Sixty-seven PWH were identified. LAI treatment duration was 216 ± 80 weeks (range 32-320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; P < 0.05). No differences were found in rilpivirine (160 ± 118 versus 189 ± 81 ng/mL; P = 0.430) and cabotegravir (1758 ± 807 versus 1969 ± 802 ng/mL; P = 0.416) trough concentrations in males (n = 55) versus females (n = 12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (n = 9) versus non-obese participants (1916 ± 905 versus 1606 ± 576 ng/mL; P = 0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load., Conclusions: At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Recent studies have highlighted the prognostic value of easily accessible inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for predicting severe outcomes in patients affected by Coronavirus disease 2019 (COVID-19). Our study validates NLR and PLR cut-off values from a prior cohort at IRCCS Policlinico San Matteo (OSM) of Pavia, Italy, across two new cohorts from different hospitals. This aims to enhance the generalizability of these prognostic indicators., Methods: In this retrospective cohort study, conducted at Milan's Ospedale Luigi Sacco (OLS) and IRCCS Ospedale Maggiore Policlinico (OMP) hospitals, we assess the predictive capacity of NLR and PLR for three main outcomes-non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) usage, invasive ventilation (IV), and death-in patients with COVID-19 at admission. For each outcome, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed separately for male and female cohorts. Distinct NLR and PLR cut-off values were used for men (7.00, 7.29, 7.00 for NLR; 239.22, 248.00, 250.39 for PLR) and women (6.36, 7.00, 6.28 for NLR; 233.00, 246.45, 241.54 for PLR), retrieved from the first cohort at OSM., Results: A total of 3599 patients were included in our study, 1842 from OLS and 1757 from OMP. OLS and OMP sensitivity values for both NLR and PLR (NLR: 24-67%, PLR: 40-64%) were inferior to specificity values (NLR: 64-76%, PLR: 55-72%). Additionally, PPVs generally remained lower (< 63%), while NPVs consistently surpassed 68% for PLR and 72% for NLR. Finally, both PLR and NLR exhibited consistently higher NPVs for more severe outcomes (> 82%) compared to NPVs for CPAP/NIV., Conclusions: Consistent findings across diverse patient populations validate the reliability and applicability of NLR and PLR cut-off values. High NPVs emphasize their role in identifying individuals less likely to experience severe outcomes. These markers not only aid in risk stratification but also guide resource allocation in emergencies or limited-resource situations., (© 2024. The Author(s).)

Background: Mpox virus (MPXV) has recently spread outside of sub-Saharan Africa. This large multicentre study was conducted in Lombardy, the most densely populated Italian region accounting for more than 40% of Italian cases. The present study aims to: i) evaluate the presence and the shedding duration of MPXV DNA in different body compartments correlating the MPXV viability with the time to onset of symptoms; ii) provide evidence of MPXV persistence in different body compartment as a source of infection and iii) characterize the MPXV evolution by whole genome sequencing (WGS) during the outbreak occurred in Italy., Material and Methods: The study included 353 patients with a laboratory-confirmed diagnosis of MPXV infection screened in several clinical specimens in the period May 24th - September 1st, 2022. Viral isolation was attempted from different biological matrices and complete genome sequencing was performed for 61 MPXV strains., Results: MPXV DNA detection was more frequent in the skin (94.4%) with the longest median time of viral clearance (16 days). The actively-replicating virus in cell culture was obtained for 123/377 (32.6%) samples with a significant higher viral quantity on isolation positive samples (20 vs 31, p < 0.001). The phylogenetic analysis highlighted the high genetic identity of the MPXV strains collected, both globally and within the Lombardy region., Conclusion: Skin lesion is gold standard material and the high viral load and the actively-replicating virus observed in genital sites confirms that sexual contact plays a key role in the viral transmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Oral human papillomavirus (HPV) is common among healthy individuals but causes and implications of persistent infections are under evaluation in the pathogenesis of head and neck neoplasms., Methods: This was a retrospective study evaluating the prevalence of high-risk (HR), probable HR and low-risk (LR) HPV types in patients reporting signs/symptoms of oral and upper respiratory tract lesions. Individuals attending between 2019 and 2022 a University Hospital in Milan, Italy, with risk factors for HPV (unprotected oral sex and/or previous documentation of HPV infection in oral and upper respiratory tract and/or another anatomical site) were included., Results: Fourteen out of 110 (12.7%) individuals tested positive for HPV DNA. The prevalence of HR-HPV and LR-HPV was 3.6% (4/110) and 9.1% (10/110), respectively. No probable/possible HR-HPV was detected. Specifically, 10/110 (9.1%) were diagnosed with 1 LR-HPV genotype, 3/110 (2.7%) were infected with 1 HR-HPV and 1/110 had 3 concomitant HR-HPV types. HPV 16 (2.7%, 3/110) and 6 (4.5%, 5/110) were the most common HR and LR types, respectively. One patient positive for HPV 16, 33 and 35 was diagnosed with cancer at the base of the tongue. Two individuals among those who tested positive for HPV DNA reported previous HPV vaccination., Conclusions: Our data, in line with observations from previous prevalence studies, support the potential role of HPV in head and neck neoplasms. HPV DNA testing should be performed in patients presenting lesions in oral/respiratory tracts and risk factors for HPV. Improvement in HPV vaccination coverage is warranted.

Purpose: Besides the well-established efficacy in preventing severe COVID-19, the impact of early treatments, namely antivirals and monoclonal antibodies (mAbs), on the time length to negativization of SARS-CoV-2 nasal swabs is still unclear. The aim of this study was to compare the efficacy of different early treatments in reducing the SARS-CoV-2 viral shedding, identifying a single drug that might potentially lead to a more rapid negativization of SARS-CoV-2 nasal swab., Methods: This was a single-centre, retrospective, observational study conducted at Ospedale Luigi Sacco in Milan. Data of high-risk COVID-19 patients who received early treatments between 23 December 2021 and March 2023 were extracted. The comparison across treatments was conducted using the Kruskall-Wallis test for continuous variables. Dunn's test with Bonferroni adjustment was performed for post-hoc comparisons of days to negativization. Secondly, a negative binomial regression adjusted for age, sex, number of comorbidities, immunosuppression, and SARS-CoV-2 vaccination status was implemented., Results: Data from 428 patients receiving early treatments were collected. The majority were treated with Nirmatrelvir/Ritonavir and were affected by SARS-CoV-2 Omicron infection with BA.2 sublineage. The median length time to SARS-CoV-2 nasal swab negativization was 9 days [IQR 7-13 days]. We found that Nirmatrelvir/Ritonavir determined a significant decrease of the length time to SARS-CoV-2 nasal swab negativization compared to mAbs (p = 0.003), but not compared to Remdesivir (p = 0.147) and Molnupiravir (p = 0.156)., Conclusion: Our findings highlight the importance of promptly treating high-risk COVID-19 patients with Nirmatrelvir/Ritonavir, as it also contributes to achieving a faster time to negative SARS-CoV-2 nasal swabs., (© 2024. The Author(s).)

Pulmonary aspergillosis mainly affects elderly patients, patients with pulmonary complications, patients with hematological malignancies, organ transplant recipients, or critically ill patients. Co-morbidities may result in a high rate of polypharmacy and a high risk of potential drug-drug interaction (pDDI)-related antifungal azoles, which are perpetrators of several pharmacokinetic- and pharmacodynamic-driven pDDIs. Here, we report the results of the first 2-year study of an outpatient clinic focusing on the management of therapies in patients with pulmonary aspergillosis. All patients who underwent an outpatient visit from May 2021 to May 2023 were included in this retrospective analysis. A total of 34 patients who were given an azole as an antifungal treatment (53% voriconazole, 41% isavuconazole, and 6% itraconazole) were included. Overall, 172 pDDIs were identified and classified as red- (8%), orange- (74%), or yellow-flag (18%) combinations. We suggested handling polypharmacy in those patients using specific diagnostic and pharmacologic interventions. As expected, red-flag pDDIs involved mainly voriconazole as a perpetrator (71%). However, nearly 30% of red-flag pDDIs were not related to antifungal therapy. These findings highlight the importance of conducting an overall assessment of the pharmacologic burden and the key role played by a multidisciplinary team for the optimization of therapies in patients with pulmonary aspergillosis.

Human papillomavirus (HPV) is the most common sexually transmitted infection, linked to several types of lesions. HPV, specifically HPV 16, accounts for most of anal cancer cases. In this study, we evaluated the proportion of samples tested positive for HPV and characterized genotypes distribution in anal specimens collected from individuals at risk of anal HPV infection attending from 2018 to 2022 a large Infectious Diseases Department in Italy. The presence of HPV DNA was investigated through a commercial kit detecting 12 HR-HPV, 8 probable/possible HR-HPV, and 8 LR-HPV genotypes. Among 1514 samples, 84% (1266/1514) resulted positive for any type of HPV. The prevalence of high-risk HPV types remained high during all the years of the study period, from 2018 to 2022, ranging from 65% to 73%. Most of HR-HPV, LR-HPV and HPV 16 positive samples were collected from men >45 years. HPV 16 was also the most frequent type in men and women. We did not observe significant variations between years in detection of HR-HPV, instead of LR-HPV, that significantly decreased. In conclusion, the high prevalence of oncogenic HPV genotypes underlines the necessity of clear anal HPV screening guidelines and, along with frequent HR-HPV coinfections, reinforces the urge to intensify the anti-HPV vaccination campaign., (© 2024 Wiley Periodicals LLC.)

Background: First-line integrase strand transfer inhibitor-based regimens have become commonly used in clinical practice over the last decade. This study aimed to analyse and compare the efficacy and safety of bictegravir (BIC) and dolutegravir (DTG) when prescribed in association with emtricitabine/tenofovir alafenamide (FTC/TAF) as part of a first-line regimen for the treatment of human immunodeficiency-1 (HIV-1) infection., Methods: Treatment-naïve people living with HIV (PLWHIV) starting a first-line regimen with either BIC/FTC/TAF (BIC group) or FTC/TAF+DTG (DTG group) were analysed. Snapshot analyses were performed after 24 and 48 weeks to evaluate virological efficacy. In addition, differences in the rate of treatment discontinuation (TD) between the two groups were evaluated using the Kaplan-Meier method and the log rank test., Results: Data from 327 PLWHIV were analysed: 140 in the DTG group and 187 in the BIC group. At 48 weeks, 90.0% of individuals in the DTG group and 86.7% of those in the BIC group achieved HIV-RNA <50 copies/mL. In total, 88 and 38 cases of TD were observed in the DTG group and BIC group, respectively. The estimated probability of maintaining the study regimen at week 48 was 59.5% in the DTG group and 84.2% in the BIC group. Analysing changes in immunological parameters after 48 weeks, median improvements of +169 cell/mm 3 (P<0.001) and +233 cell/mm 3 (P<0.001) were observed in the DTG group and the BIC group, respectively., Conclusions: Both BIC and DTG, in combination with FTC/TAF, show promising efficacy and safety as first-line strategies in clinical practice, with favourable immunological recovery even in the short term., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objectives: We aimed to study whether people living with HIV (PLWH) are at higher risk of in-hospital COVID-19 mortality compared to the general population (GenPop)., Methods: This was a retrospective study in 19 Italian centers (February 2020 to November 2022) including hospitalized PLWH and GenPop with SARS-CoV-2 infection. The main outcome was in-hospital mortality. Competing risk analyses by Fine-Gray regression model were used to estimate the association between in-hospital mortality and HIV status/age., Results: A total of 7399 patients with COVID-19 were included, 239 (3.2%) PLWH, and 7160 (96.8%) GenPop. By day 40, in-hospital death occurred in 1283/7160 (17.9%) among GenPop and 34/239 (14.2%) among PLWH. After adjusting for potential confounders, compared to GenPop <65 years, a significantly higher risk of death was observed for GenPop ≥65 (adjusted subdistribution hazard ratio [aSHR] 1.79 [95% CI 1.39-2.31]), PLWH ≥65 (aSHR 2.16 [95% CI 1.15-4.04]), PLWH <65 with CD4 ≤200 (aSHR 9.69 [95% CI 5.50-17.07]) and PLWH <65 with CD4 201-350 (aSHR 4.37 [95% CI 1.79-10.63]), whereas no evidence for a difference for PLWH <65 with CD4 >350 (aSHR 1.11 [95% CI 0.41-2.99])., Conclusions: In PLWH aged <65 years a CD4 ≤350 rather than HIV itself seems the driver for the observed higher risk of in-hospital mortality. We cannot however rule out that HIV infection per se is the risk factor in those aged ≥65 years., Competing Interests: Declarations of competing interest A Giacomelli reports speakers’ honoraria for ViiV Healthcare and Gilead Sciences, advisor for Janssen-Cilag and Mylan; RG reports payments to her institution from Gilead Sciences, speakers’ honoraria for ViiV Healthcare, Merck Sharp and Dohme and Gilead Sciences, advisor for Thera Technologies, Janssen-Cilag and Gilead Sciences; GR reports consultancies/advisory from ViiV Healthcare, GSK, Merck Sharp and Dohme and Gilead Sciences; A Gori received speaker's honoraria and fees for attending advisory boards from ViiVHealthcare, Gilead, Janssen-Cilag, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer and Novartis and received research grants from ViiV, Bristol-Myers Squibb, and Gilead; AM received speakers’ honoraria from Gilead Sciences, and ViiV Healthcare, travel fee from Viiv Healthcare and participated in advisory boards sponsored by ViiV Healthcare; AV received an institutional grant from Gilead Sciences, speakers’ honoraria/educational activities from Merck Sharp & Dohme and Janssen-Cilag, and served an advisor for Janssen-Cilag; MM received speakers’ honoraria from ViiV Healthcare; LT reports consultancies/advisory from Viiv Healthcare, Gilead Sciences and Janssen-Cilag and institutional fellowship from Gilead Sciences; G Marchetti participated to advisory boards of Gilead Sciences, ViiV Healthcare, Angelini and Janssen-Cilag, and received travel grants from ViiV Healthcare and Janssen-Cilag; AdM participated in advisory board of Gilead Sciences, ViiV Healthcare, Merck Sharp and Dohme, Pfizer and GSK and reports research grant from Gilead Science, ViiV Healthcare, Merck Sharp and Dohme, GSK and Janssen-Cilag; AA received Research grants from Gilead Sciences, AstraZeneca, ViiV Healthcare and Honoraria from Gilead Science, AstraZeneca, GSK, Pfizer, Merck Sharp and Dohme, Moderna, Mylan, Janssen-Cilag, ViiV Healthcare; AT, SDB, SA, G Mancarella, FMF, ADV, VM, MA and ACL have nothing to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We aimed to estimate the diagnostic latency of patients with visceral leishmaniasis (VL). A monocentric retrospective observational study was conducted including all confirmed cases of VL diagnosed from January 2005 to March 2022. Epidemiological and clinical characteristics of patients with VL were collected. The diagnostic latency was defined as the number of days between the first contact with a health-care provider for signs and/or symptoms referable to VL and the laboratory diagnosis of leishmaniasis. Twenty-four cases of VL were included in the study, mostly male (75%) and Italians (79.2%), with a median age of 40 years [Inter Quartile Range (IQR 30-48)]. Fourteen (58.3%) VL cases were people living with HIV (PLWH) and 4 (16.6%) subjects were on immunosuppressive therapy. For VL the median diagnostic latency was 54 days (IQR 28-162). The shorter diagnostic latency was observed in PLWH [31 days (IQR 20-47)] followed by immunocompetent patients [160 days (IQR 133-247)] and those on immunosuppressive therapy [329 days (IQR 200-678)]. Twelve patients (50%) reported at least one medical encounter before the diagnosis of VL and 6 patients received a wrong therapy. Diagnostic delay in VL was significant in patients under immune suppressive treatment., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: Predictors of Respiratory Syncytial Virus (RSV) infection and determinants of RSV unfavorable outcomes are still unclear. We assessed RSV burden and investigated the risk factors associated with RSV positive swab and RSV severe disease., Methods: A retrospective, single center, cohort study included all consecutive patients referred to the emergency department of L. Sacco University Hospital (Milan) with flu-like symptoms or acute respiratory failure (aRF) tested per protocol for SARS-CoV-2, RSV, Influenza A (InvA) during the 2022-2023 autumn/winter season. Clinical characteristics and patients' outcomes were registered. Respiratory failure, need for respiratory support, shock, sepsis or in-hospital death defined severe disease., Main Findings: The analysis included 717 patients (65.1% negative swab, 14.1% InvA, 8.5% RSV, 8.6% SARS-CoV-2, 3.6% other viruses). Compared with the study cohort, RSV patients had the highest occurrence of aRF (62.7%) and severe disease (70.5%); mortality was similar to InvA (6.6% vs 5.9%, p = 0.874). Compared with InvA patients, RSV patients were older (p = 0.009), had higher Charlson index (p = 0.001), higher prevalence of chronic heart failure (p = 0.001) and were more frequently on ICS (p = 0.026) and immunosuppressants (p = 0.018). Heart failure [OR (95%CI):3.286 (1.031-10.835); p = 0.041], chronic exposure to ICS [OR (95%CI):2.377 (1.254-4.505); p = 0.008] and immunosuppressants [OR (95%CI):3.661 (1.246-10.754); p = 0.018] predicted RSV infection. Glycaemia ≥120 mg/dL [OR (95%CI):5.839 (1.155-29.519); p = 0.033], leucocytes ≥8000 cells/μL [OR (95%CI):5.929 (1.090-32.268); p = 0.039], and past/active smoking [OR (95%CI):7.347 (1.301-41.500); p = 0.024] predicted severe RSV disease., Conclusions: RSV infection is associated with significant mortality and morbidity. Preventive strategies for RSV infection such as vaccination are highly warranted, especially in older patients with cardiovascular and chronic respiratory conditions., Competing Interests: Declaration of competing interest PS reports fees for consulting from Gilead. DR, MRG, SGR, AL FD, AG, SA and GR have no conflict of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Real-life comparisons of dolutegravir/rilpivirine (DTG/RPV) and DTG/lamivudine (3TC) regimens in people living with human immunodeficiency virus (PLWHIV) who switched from a standard three-drug regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are missing. This study aimed to compare DTG/3TC and DTG/RPV in virologically suppressed patients (HIV-RNA < 50 copies/mL) coming from any NNRTI-based regimen in terms of discontinuation due to virologic failure (VF) discontinuation rates due to all causes, and adverse events. As a secondary outcome, we evaluated the difference in creatinine, total cholesterol, CD4, and triglycerides from baseline to weeks 48 after the switch. Of the 415 PLWHs included in the study, 278 (66.9%) switched to DTG/3TC, and 137 (33.1%) switched to DTG/RPV. Overall, 48 PLWHs (11.6%) discontinued the treatment:38 with DTG/3TC and 10 with DTG/RPV with similar discontinuation rates: 5.01 × 100 py (95% confidence interval [CI] 3.64-6.94) and 4.66 × 100 py (95% CI 2.51-8.67), respectively. The most common reason for discontinuation was toxicity (26 patients, 22/278 [7.9%] in the DTG/3TC group and 4/137 [2.9%] in the DTG/RPV group), mainly neurologic toxicity (never above grade 2). We found no differences in discontinuation rates due to treatment adverse events. Two study participants experienced virological failure in the DTG/3TC arm. We observed no significant difference in CD4 cell counts, lipid parameters, or renal function between the two groups at 48 weeks. This study demonstrated that, in clinical practice, a two-drug regimen with DTG/3TC or DTG/RPV is characterized by a low discontinuation rate and VF in virologically suppressed PLWHs switched from an NNRTI-based three antiretroviral drugs regimen., (© 2023 Wiley Periodicals LLC.)

The World Health Organization (WHO) defines neglected tropical diseases (NTDs) as a diverse group of primarily infectious diseases, which disproportionately affect poor and marginalized populations worldwide. In this context, NTDs are responsible for important morbidity and mortality and justify a global response. Moreover, NTDs are relatively neglected by research and development as well as by funding, if compared with the magnitude of the public health problem they represent. This happens even though, unlike other infectious diseases, they can be prevented, controlled and eliminated by targeted public health interventions. NTDs are mainly prevalent in communities from low-income countries in tropical and sub-tropical areas but are also present in upper–middle-income countries, including several in Europe. Here, we provide an update on the most relevant parasitic endemic or imported NTDs in Italy and illustrate the rationale for the establishment of the Italian network on NTDs, an alliance of scientific societies, institutes, foundations, universities and non-profit organizations united to fight NTDs.

Critically ill COVID-19 patients are at an increased risk of bloodstream infections (BSIs). We performed a retrospective observational single-center study on COVID-19 patients admitted to intensive care unit (ICU) to assess the incidence of BSIs in four consecutive periods: 21 February-31 July 2020 (W1), 1 August 2020-31 January 2021 (W2), 1 February-30 September 2021 (W3) and 1 October 2021 and 30 April 2022 (W4). BSIs that occurred 48 h after ICU admission were included. The crude incidence of BSIs was estimated by means of Poisson distribution normalized to 1000 patient-days. A total of 404 critically ill COVID-19 patients were admitted to ICU, of whom 284 (61%) developed at least one episode of BSI with an overall crude incidence of 87 events every 1000 patient-days (95% CI 77-98) without a significant difference in consecutive epidemic periods ( p = 0.357). Gram-positive bacteria were the most frequent etiological agents of BSIs, contributing to 74.6% episodes. A progressive decrease in BSIs due to Enterococcus spp. was observed (W1 57.4%, W2 43.7%, W3 35.7% and W4 32.7%; p = 0.004). The incidence of BSIs remained stable during different epidemic periods. Enterococcus spp. prevalence was significantly reduced, although still accounted for one third of BSIs in more recent epidemic periods.

Competing Interests: Conflict of interest None to declare.

Mpox (formerly Monkeypox), a neglected tropical disease once confined to Central and West Africa, emerged as a global epidemic outbreak in May, 2022 with 87,529 cases reported as of May, 23, 2023. It predominantly affected men (96.2%) who have sex with men (84-100%), although other transmission routes have been reported, including occupational exposure and vertical transmission. Concomitant HIV infection has been recorded in 21-46.9% and pre-exposure prophylaxis against HIV infection has been reported in 11-57% of published cases. The current outbreak clinical presentation differs from endemic cases with prodromal symptoms that could be absent: the number of lesions is generally low, with skin lesions predominantly localised in the ano-genital areas and frequent lesions present in different stages of progression (i.e., asynchronous). Asymptomatic Mpox infection can occur in 1.8-6.5% of at-risk subjects. People living with HIV with severe immunodeficiency (less than 100 CD4+ lymphocytes per microliter) are at risk of more severe clinical manifestations and death. According to a systematic review and meta-analysis, the hospitalisation rate is around 6% and the observed case-fatality rate is less than 0.1%. Tecovirimat is the drug of choice for treating severe cases although there is no evidence of efficacy from randomised controlled trials. Immunization with a live non-replicating vaccine (JYNNEOS) effectively reduces the disease's incidence., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose concerning this work

Most antimicrobial drugs need an intravenous (IV) administration to achieve maximum efficacy against target pathogens. IV administration is related to complications, such as tissue infiltration and thrombo-phlebitis. This systematic review aims to provide practical recommendations about diluent, pH, osmolarity, dosage, infusion rate, vesicant properties, and phlebitis rate of the most commonly used antimicrobial drugs evaluated in randomized controlled studies (RCT) till 31 March 2023. The authors searched for available IV antimicrobial drugs in RCT in PUBMED EMBASE ® , EBSCO ® CINAHL ®, and the Cochrane Controlled Clinical trials. Drugs' chemical features were searched online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, osmolarity >600 mOsm/L, high incidence of phlebitis reported in the literature, and vesicant drugs need the adoption of utmost caution during administration. We evaluated 931 papers; 232 studies were included. A total of 82 antimicrobials were identified. Regarding antibiotics, 37 reach the "caution" criterion, as well as seven antivirals, 10 antifungals, and three antiprotozoals. In this subgroup of antimicrobials, the correct vascular access device (VAD) selection is essential to avoid complications due to the administration through a peripheral vein. Knowing the physicochemical characteristics of antimicrobials is crucial to improve the patient's safety significantly, thus avoiding administration errors and local side effects.

Background: Chagas disease (CD) is considered to be highly endemic in El Salvador, where its prevalence is estimated to be 1.3-3.7%. Although more than 40,000 migrants from El Salvador are currently living in Europe (particularly in Spain and Italy), there are few data regarding the prevalence of CD in this population. The aim of this study was to evaluate the prevalence of CD among Salvadorans living in Italy., Methods: A cross-sectional serological survey of CD among Salvadorans living in the metropolitan area of Milan was carried out between October 2017 and December 2019. The participants' blood samples were tested for Trypanosoma cruzi antibodies using two different serological assays. The collected demographic data included their biological sex, province of origin, the type of housing in their country of origin, and family history of CD., Results: Of the 384 subjects who voluntarily participated in the study, five (1.3%, most coming from La Paz) were positive to both serological assays and therefore conclusively diagnosed as having CD. Five other subjects had discrepant serological results but were not positive to a third assay. Three of the five subjects with a diagnosis of CD completed medical staging, one of whom had chronic disease (digestive and cardiac involvement)., Conclusions: The prevalence of CD among Salvadorans living in Milan is similar to that estimated by the WHO in 2010. Although they are often overlooked in CD surveys, Salvadoran migrants should be included in CD control programs in countries in which the disease is not endemic.

In 2022, we opened an outpatient clinic for the management of polypharmacy and potential drug-drug interactions (pDDIs) in patients with mycobacterial infection (called GAP-MyTB). All patients who underwent a GAP-MyTB visit from March 2022 to March 2023 were included in this retrospective analysis. Fifty-two patients were included in the GAP-MyTB database. They were given 10.4 ± 3.7 drugs (2.8 ± 1.0 and 7.8 ± 3.9 were, respectively, antimycobacterial agents and co-medications). Overall, 262 pDDIs were identified and classified as red-flag (2%), orange-flag (72%), or yellow-flag (26%) types. The most frequent actions suggested after the GAP-MyTB assessment were to perform ECG (52%), therapeutic drug monitoring (TDM, 40%), and electrolyte monitoring (33%) among the diagnostic interventions and to reduce/stop proton pump inhibitors (37%), reduce/change statins (14%), and reduce anticholinergic burden (8%) among the pharmacologic interventions. The TDM of rifampicin revealed suboptimal exposure in 39% of patients that resulted in a TDM-guided dose increment (from 645 ± 101 to 793 ± 189 mg/day, p < 0.001). The high prevalence of polypharmacy and risk of pDDIs in patients with mycobacterial infection highlights the need for ongoing education on prescribing principles and the optimal management of individual patients. A multidisciplinary approach involving physicians and clinical pharmacologists could help achieve this goal.

Background: Despite the availability of potent antiretroviral drugs, the management of human immunodeficiency virus (HIV) infection still presents some important challenges, especially in older patients who often experience age-related comorbidities and complex polypharmacy., Objective: To describe the results of our 6 year experience with the outpatient clinic [Gestione Ambulatoriale Politerapie (GAP)] for the management of polypharmacy in people living with HIV (PLWH)., Methods: Demographic characteristics, antiretroviral regimens, and number and type of comedications were collected in all PLWH included in the database of GAP from September 2016 to September 2022. Therapies were stratified based on the number of anti-HIV drugs (dual versus triple regimens) and on the presence of pharmacokinetic boosters (ritonavir or cobicistat)., Results: A total of 556 PLWH were included in the GAP database. Overall, the enrolled patients were administered 4.2 ± 2.7 drugs (range 1-17) in addition to antiretroviral therapies. The number of comedications greatly increased with age (3.0 ± 2.2 versus 4.1 ± 2.5 versus 6.3 ± 3.2 in PLWH aged < 50 versus 50-64 versus > 65 years; p < 0.001 for all comparisons). PLWH on dual antiretroviral therapies were significantly older (58 ± 9 versus 54 ± 11 years; p < 0.001) and were concomitantly treated with more drugs (5.1 ± 3.2 versus 3.8 ± 2.5; p < 0.001) compared with those on triple therapies. A significant reduction of boosted antiretroviral regimens (53% versus 23%; p < 0.001) and in the number of comedications (4.0 ± 2.9 versus 3.1 ± 2.2 drugs; p < 0.001) was observed in the subgroup of patients (n = 198) with two GAP visits., Conclusions: The high prevalence of polypharmacy in PLWH, especially among older adults, place these patients at high risk for clinically relevant drug-drug interactions (DDIs). A multidisciplinary approach involving physicians and clinical pharmacologists could help to optimize medication regimens associated with reduced risk., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)