Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status.

SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94 % in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.

Disinfectant caps in vitro effectiveness.

Background: Catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality among hospitalized patients. Different studies suggest that the use of disinfectant caps (DCs) significantly reduces the rate of CRBSIs. The first purpose of this study is to analyze, through an in-vitro-model, the antiseptic effect of DCs produced by two manufacturers; the second aim is to assess potential differences in terms of effectiveness between the two manufacturers' products. Methods: A know concentration of thirteen different microorganisms was incubated with the sponge drenched in antimicrobial fluid inside DCs and cultured through several assays to investigate the disinfectant effectiveness of some commercially available caps. Disinfectant properties were evaluated under two different conditions: baseline (DCs placed on the needle-free connectors (NFCs) and stress test (DCs directly applied to the catheter hub). Results: Both manufacturers overcame the basal tests (fourteen different assays). Regarding stress tests: the only significant bacterial load was found for Serratia marcescens (104 CFU/mL in ICU Medical™), both at 90 and 180 minutes after incubation; due to the low load, MDR Acinetobacter baumannii was not considered significant (<103 CFU/mL in BD PureHub™). Conclusions: Our results confirm what was reported in BD PureHub™ datasheet and add data not previously shown by ICU Medical™. Moreover, no difference was observed between the two manufacturers products: the use of both DCs on NFCs was able to reclaim the catheter lumen. These findings support the routine use of DCs with NFCs, as part of a structured bundle of interventions, to reduce the incidence of CRBSIs.

Brief Report: Impact of the COVID-19 Pandemic on Virological Suppression in People Living With HIV Attending a Large Italian HIV Clinic.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HIV suppression rates in people living with HIV (PLWH) attending a large Italian HIV clinic. SETTING: The HIV outpatient clinic of the Infectious Diseases Department of Luigi Sacco Hospital, Milan, Italy, which serves more than 5000 PLWH per year. METHODS: A before and after quasi-experimental study design was used to make a retrospective assessment of the monthly trend of HIV-RNA determinations of ≥50 among the PLWH attending our clinic, with "before" being the period from January 1, 2016 to February 20, 2020, and "after" being the period from February 21, 2020 to December 31, 2020 (the COVID-19 period). Interrupted time series analysis was used to evaluate any changes in the trend. RESULTS: During the study period, 70,349 HIV-RNA viral load determinations were made, and the percentage of HIV-RNA viral load determinations of <50 copies/mL increased from 88.4% in 2016 to 93.2% in 2020 (P < 0.0001). There was a significant monthly trend toward a decrease in the number of HIV-RNA determinations of ≥50 copies/mL before the pandemic (ß -0.084; standard error 0.015; P < 0.001), and this did not significantly change after it started (ß -0.039, standard error 0.161; P = 0.811). CONCLUSIONS: A high prevalence of viral suppression was maintained among the PLWH referring to our clinic, despite the structural barriers raised by the COVID-19 pandemic. The use of simplified methods of delivering care (such as teleconsultations and multiple antiretroviral treatment prescriptions) may have contributed to preserving this continuum.

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy.

BACKGROUND: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. METHODS: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. RESULTS: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). CONCLUSION: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.

Strategic use of dual regimens of boosted protease inhibitors plus maraviroc in poorly adherent subjects in view of long-acting drugs: A retrospective study.

In view of the forthcoming long-acting antiretrovirals, measures should be taken to prevent the selection of HIV drug resistance mutations. All subjects who had been switched to boosted protease inhibitors plus maraviroc (bPIs/MVC) with baseline HIV-1 RNA >50 copies/mL between June, 2014, and April, 2015, were retrospectively evaluated. HIV-1 RNA, CD4+ T-cells, serum glucose, creatinine, ALT, and adverse events were controlled every 3 to 4 months. We retrospectively analyzed 44 patients: 18 were taking darunavir/ritonavir (DRV/r) and 26 atazanavir/ritonavir (ATV/r) once daily, plus MVC 300 mg once daily. Seven subjects were in CDC stage C. All had a follow-up of at least 24 weeks, 28 exceeded 48 weeks, and 21 exceeded 72 weeks. All had experienced at least 1 viral failure and had selected at least 1 resistance-associated mutation (RAM). At baseline, 38 had plasma HIV-1 RNA 50-499 copies/mL and 6 had ≥500. At week 24, none had viremia >500 and 30 (68.2%) had suppressed HIV-1 RNA below 50 copies/mL. Of the subgroup with 48 weeks' follow-up, 23 had HIV-1 RNA 50-499 copies/mL, 5 had ≥500, and 20/28 suppressed to <50 copies/mL. Of the longest observed subgroup (72 weeks), 17 had HIV-1 RNA 50-499 copies/mL, and 4 had ≥500 copies/mL and 15/21 (71.4%) suppressed to <50 copies/mL. This combination allowed fair suppression of viral replication, with minor genotypic evolution in 6 subjects, and seems to be a feasible strategy to prevent damaging future options.

Impact of therapeutic drug monitoring of antiretroviral drugs in routine clinical management of patients infected with human immunodeficiency virus and related health care costs: a real-life study in a large cohort of patients.

BACKGROUND: Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with human immunodeficiency virus (HIV). Studies have documented high interindividual variability in the pharmacokinetics of antiretroviral drugs, which may impair the success of HAART if not managed properly. Therapeutic drug monitoring (TDM) is a useful diagnostic tool that helps clinicians to optimize drug doses so that drug concentrations associated with the highest therapeutic efficacy are obtained with a reduced risk of concentration-dependent adverse effects. The aim of this study was to assess whether use of TDM improves clinical outcomes and cost of illness. METHODS: A retrospective cohort study was conducted at L Sacco University Hospital in Milan, Italy, in HIV-infected patients aged ≥18 years with at least one prescription of antiretroviral drugs for which TDM was applied. The inclusion period was from January 2010 to December 2011, with a follow-up period of up to 12 months. Laboratory and administrative databases were analyzed and matched with each other. RESULTS: The cohort consisted of 5,347 patients (3,861 males and 1,486 females) of mean age 43.9±12.5 years. We found that TDM had been used in 143 of these patients, among whom adherence with therapy was significantly higher than among those in whom TDM had not been used (94% versus 78%). In TDM-controlled patients, the mean length of HIV-related hospitalization stay and mean cost of hospitalization were significantly reduced with respect to those observed in the group in which TDM had not been used (7.21 days versus 29.47 days and €293 versus €688, respectively). CONCLUSION: Inclusion of TDM as part of routine clinical optimization of drug dosing in HIV-infected patients is associated with higher adherence to therapy, reduced length of hospitalization stay, and reduced cost of illness.