Doravirine Plus Integrase Strand Transfer Inhibitors as a 2-Drug Treatment-Switch Strategy in People Living with HIV: The Real-Life DORINI Multicentric Cohort Study.

Background: Few data are available about the efficacy, durability, and tolerability of doravirine (DOR) + integrase strand inhibitors (INI) as a switching strategy among antiretroviral therapy (ART)-experienced people living with HIV (PLWH).

Setting: Retrospective, multicenter cohort study investigating the durability, efficacy, and tolerability of 2 off-label drug associations of DOR + INI among ART-experienced PLWH.

Methods: The study included PLWH who switched to DOR combined with either raltegravir (RAL) or dolutegravir (DTG) between June 1, 2020, and December 31, 2021, with at least 1 follow-up (FU) visit.

Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review.

Introduction: Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients.

Methods: Narrative review based on a literature search through PubMed and Cochrane using the following keywords: "multi-drug resistant (MDR)", "extensively drug resistant (XDR)", "pan-drug-resistant (PDR)", "difficult-to-treat (DTR) Gram-negative infection," "antibiotic duration therapy", "antibiotic combination therapy" "antibiotic monotherapy" "Gram-negative bacteremia", "Gram-negative pneumonia", and "Gram-negative intra-abdominal infection".

Results: Current literature data suggest adopting longer (≥10-14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45-50%), MDR (35%), XDR (15-20%), PDR (5.

Comparison of multiple definitions for ventilator-associated pneumonia in patients requiring mechanical ventilation for non-pulmonary conditions: preliminary data from PULMIVAP, an Italian multi-centre cohort study.

Objectives: To compare intensivist-diagnosed ventilator-associated pneumonia (iVAP) with four established definitions, assessing their agreement in detecting new episodes.

Methods: A multi-centric prospective study on pulmonary microbiota was carried out in patients requiring mechanical ventilation (MV). Data collected were used to compare hypothetical VAP onset according to iVAP with the study consensus criteria, the European Centre for Disease Control and Prevention definition, and two versions of the latter adjusted for leukocyte count and fever.

Management of Polypharmacy and Potential Drug-Drug Interactions in Patients with Mycobacterial Infection: A 1-Year Experience of a Multidisciplinary Outpatient Clinic.

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.

Polypharmacy and Aging in People Living with HIV: 6 Years of Experience in a Multidisciplinary Outpatient Clinic.

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.

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System.

Background: In this study, we fill this gap in knowledge by updating the safety profile of ubrogepant and rimegepant via disproportionality analysis in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), a US-based database registering spontaneous reports.

Research Design And Methods: ASCII files of quarterly extraction of FAERS data were downloaded from the FDA website up to the 3 quarter (Q3) of 2021 (last accessed 03/02/2022). Disproportionality analysis was done using the Reporting Odds Ratio (ROR) as a disproportionality measure.

Hematological toxicities associated with linezolid therapy in adults: key findings and clinical considerations.

Introduction: Linezolid can cause serious adverse effects including thrombocytopenia and anemia. Here, we focus specifically on linezolid-related hematological toxicity in adult patients requiring prolonged drug treatment.

Areas Covered: We review the available evidence on the likelihood of hematological toxicity in adult patients treated with linezolid, with a focus on the main risk factors and strategies to prevent this adverse event.

Management of diabetes mellitus in people living with HIV: A single-center experience.

Diabetes mellitus (DM) is more common in people living with HIV (PLWH) than in HIV-negative patients. Here we aimed to describe the response of PLWH with DM to glucose-lowering therapies in a reference hospital of northern Italy. 200 PLWH and DM were identified from the database of our clinic.

Dynamics of Lipid Profile in Antiretroviral-Naïve HIV-Infected Patients, Treated with TAF-Based Regimens: A Multicenter Observational Study.

Background: The introduction of tenofovir alafenamide (TAF) in antiretroviral therapy has deeply modified the choice of the backbone for different treatment regimens, allowing the prevention of the bone and renal toxicity that was related to the previous formulation of tenofovir disoproxil fumarate (TDF). At the same time, literature data show an onset of dyslipidemia after a switch from TDF to TAF. To better understand the possible role of TAF in dyslipidemia, antiretroviral-naïve HIV-infected patients were evaluated, comparing those treated with TAF/emtricitabine with those with abacavir/lamivudine.

"CATCH" Study: Correct Antibiotic Therapy in Continuous Hemofiltration in the Critically Ill in Continuous Renal Replacement Therapy: A Prospective Observational Study.

The proper posology of antibiotics in the critically ill in CRRT is difficult to assess. We therefore performed a prospective observational cohort study to make clear hints in this topic. Our results reveal a high Sieving Coefficient for all antibiotics, equal to or higher than those described in previous papers.

Antibiotic Therapy in the Critically Ill with Acute Renal Failure and Renal Replacement Therapy: A Narrative Review.

The outcome for critically ill patients is burdened by a double mortality rate and a longer hospital stay in the case of sepsis or septic shock. The adequate use of antibiotics may impact on the outcome since they may affect the pharmacokinetics (Pk) and pharmacodynamics (Pd) of antibiotics in such patients. Acute renal failure (ARF) occurs in about 50% of septic patients, and the consequent need for continuous renal replacement therapy (CRRT) makes the renal elimination rate of most antibiotics highly variable.

Exploring the underlying mechanisms of drug-induced impulse control disorders: a pharmacovigilance-pharmacodynamic study.

Introduction: Impulse control disorders (e.g. pathological gambling, hypersexuality) may develop as adverse reactions to drugs.

A large series of molecular and serological specimens to evaluate mother-to-child SARS-CoV-2 transmission: a prospective study from the Italian Obstetric Surveillance System.

Objectives: To assay the presence of the SARS-CoV-2 genome in vaginal, rectal, and placental swabs among pregnant women and in newborn nasopharyngeal swabs and to investigate the immunological response and maternal antibody transfer through the umbilical cord blood and milk of unvaccinated mothers.

Methods: Vaginal, rectal, and placental specimens, maternal and neonatal serum, and milk were collected from a wide cohort of pregnant Italian women with confirmed SARS-CoV-2 infection admitted to the hospital between February 25, 2020 and June 30, 2021. Samples were tested in selected reference laboratories according to a shared interlaboratory protocol.

The Issue of Pharmacokinetic-Driven Drug-Drug Interactions of Antibiotics: A Narrative Review.

Patients in intensive care units (ICU) are at high risk to experience potential drug-drug interactions (pDDIs) because of the complexity of their drug regimens. Such pDDIs may be driven by pharmacokinetic or pharmacodynamic mechanisms with clinically relevant consequences in terms of treatment failure or development of drug-related adverse events. The aim of this paper is to review the pharmacokinetic-driven pDDIs involving antibiotics in ICU adult patients.

Effects of the androgen receptor inhibitor enzalutamide on the pharmacokinetics of dolutegravir and tenofovir: a case report.

Enzalutamide is an androgen receptor inhibitor used for the treatment of prostate cancer. Although enzalutamide causes a favorable adverse effect profile, it might cause drug-drug interactions with some antiretrovirals. No major differences on the main dolutegravir and tenofovir pharmokinetocs were observed in this case report when comparing baseline assessments with those following the introduction of enzalutamide, also when given at higher doses, in a 63-year-old male living with HIV and prostate cancer.

Antihypertensive drugs and brain function: mechanisms underlying therapeutically beneficial and harmful neuropsychiatric effects.

A bidirectional relationship exists between hypertension and psychiatric disorders, including unipolar and bipolar depression, anxiety, post-traumatic stress disorder (PTSD), psychosis, schizophrenia, mania, and dementia/cognitive decline. Repurposing of antihypertensive drugs to treat mental disorders is thus being explored. A systematic knowledge of the mechanisms of action and clinical consequences of the use of antihypertensive agents on neuropsychiatric functions has not been achieved yet.

Lacosamide effectiveness and tolerability in patients with drug-resistant epilepsy and severe disability under polytherapy: Therapy optimization as emerging from an observational study.

Objective: We explored the efficacy and safety of lacosamide combined with inhibitors of fast-inactivated sodium channels or with other antiepileptic drugs, in patients with drug refractory focal epilepsy associated with intellectual or psychiatric disability.

Methods: Observational study of lacosamide including the monitoring of lacosamide trough plasma levels and of electroencephalograms.

Results: We followed up 44 patients from the start of lacosamide therapy for up to 3 years, with a clinical, electroencephalogram (EEG), and pharmacological follow-up.