Remdesivir treatment in hospitalized patients affected by COVID-19 pneumonia: A case-control study.

To date the optimal antiviral treatment against severe coronavirus disease 2019 (COVID-19) has not been proven; remdesivir is a promising drug with in vitro activity against several viruses, but in COVID-19 the clinical results are currently not definitive. In this retrospective observational study, we analyzed the clinical outcomes (survival analysis, efficacy, and safety) in a group of hospitalized patients with COVID-19 treated with remdesivir in comparison with a control group of patients treated with other antiviral or supportive therapies. We included 163 patients treated with remdesivir and 403 subjects in the control group; the baseline characteristics were similar in the two groups; the mortality rate was higher in the control group (24.8% vs. 2.4%, p < 0.001), the risk of intensive care unit (ICU) admission was higher in the control group (17.8% vs. 9.8%, p = 0.008); hospitalization time was significantly lower in patients treated with remdesivir (9.5 vs. 12.5 days, p < 0.001). The safety of remdesivir was good and no significant adverse events were reported. In multivariate analysis, the remdesivir treatment was independently associated with a 34% lower mortality rate (odds ratio = 0.669; p = 0.014). In this analysis, the treatment with remdesivir was associated with lower mortality, lower rate of ICU admission, and shorter time of hospitalization. No adverse events were observed. This promising antiviral treatment should also be confirmed by other studies.

Role of the early short-course corticosteroids treatment in ARDS caused by COVID-19: A single-center, retrospective analysis.

PURPOSE: Severe coronavirus disease 2019 (COVID-19) is strongly related to interstitial pneumonia with frequent development of acute respiratory distress syndrome (ARDS). The role of corticosteroids (CS) treatment in these patients is still controversial. Some studies evidenced a possible role of an early short-term course of CS treatment in the treatment of severe pneumonia. PATIENTS AND METHODS: This is a single-center, retrospective study considering the patients with confirmed COVID-19 pneumonia admitted to our hospital between 9th March and 15th June 2020. Two groups were considered: early high-dose of methyl-prednisolone (eHDM; n â€‹= â€‹31) and the control group (n â€‹= â€‹52). Patients in the eHDM group received the dose of 5-8 â€‹mg/kg/day of methyl-prednisolone for 2 consecutive days. Primary outcome was the mortality evaluation; secondary outcomes were clinical improvement, side-effects and laboratory/radiographic changes. RESULTS: Significant differences between the two groups were: length of hospitalization (21.5 vs 28.4 days, p â€‹= â€‹0.026), length of non-invasive ventilation (NIV) or mechanical ventilation (11.5 vs 14.5 days, p â€‹= â€‹0.031), death (5 vs 12, p â€‹= â€‹0.006) and clinical improvement (16 vs 11, p=0.018). The following factors were related to in-hospital mortality in the multivariate analysis: comorbidities (OR â€‹= â€‹2.919; 95%CI â€‹= â€‹1.515-16.705; p<0.001), days from the onset of symptoms and the hospital admission (OR â€‹= â€‹1.404; 95%CI â€‹= â€‹1.069-12.492; p â€‹= â€‹0.011), PaO2/FiO2 (P/F) ratio (OR â€‹= â€‹3.111; 95%CI â€‹= â€‹2.334-16.991; p â€‹= â€‹0.009) and eHDM treatment (OR â€‹= â€‹0.741; 95%CI â€‹= â€‹0.129-0.917; p â€‹= â€‹0.007). CONCLUSION: The eHDM is an interesting and promising approach in the ARDS related to COVID-19 pneumonia, which reduces mortality, length of hospitalization and the need for mechanical ventilation.

Genomic Characterization of a New Biofilm-Forming and Adhesive ST398 Human-Adapted MSSA Lineage Causing Septic Knee Arthritis Following Surgical Reconstruction.

Methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen commonly found in bone and joint infections, including septic arthritis. S. aureus virulence and the frailty of affected patients can cause several complications; a prompt and specific antibiotic treatment can positively affect the outcome of patients. We carried out an in-depth genomic characterization by Illumina whole genome sequencing and bioinformatics of two biofilm-producing M1 and M2 ST398 MSSA causing septic knee arthritis not-responding to antimicrobial therapy. The strains were characterized for antibiotic resistance, biofilm and adhesive properties as well as genomics, single nucleotide polymorphism phylogeny, resistomics and virulomics. Our results showed that M1 and M2 MSSA were ST398-t1451-agrI-Cap5, susceptible to cefoxitin and resistant to erythromycin and clindamycin, traits consistent with the lack of the SCCmec-locus and the presence of the sole blaZ and ermT. Furthermore, M1 and M2 were biofilm-producing and largely potentially adhesive strains, as indicated by the adhesion gene profile. Our data characterized a new human-adapted ST398 MSSA lineage, representing a "fusion" between the human-animal independent ST398 and the Livestock Associated (LA) ST398 lineages, forming biofilm and genomically predicted high adhesive, characterized by different genomic adaptation conferring a great ability to adhere to the host's extracellular matrix causing septic knee arthritis.

Lung Ultrasound-Implemented Diagnosis of Acute Decompensated Heart Failure in the ED: A SIMEU Multicenter Study.

BACKGROUND: Lung ultrasonography (LUS) has emerged as a noninvasive tool for the differential diagnosis of pulmonary diseases. However, its use for the diagnosis of acute decompensated heart failure (ADHF) still raises some concerns. We tested the hypothesis that an integrated approach implementing LUS with clinical assessment would have higher diagnostic accuracy than a standard workup in differentiating ADHF from noncardiogenic dyspnea in the ED. METHODS: We conducted a multicenter, prospective cohort study in seven Italian EDs. For patients presenting with acute dyspnea, the emergency physician was asked to categorize the diagnosis as ADHF or noncardiogenic dyspnea after (1) the initial clinical assessment and (2) after performing LUS ("LUS-implemented" diagnosis). All patients also underwent chest radiography. After discharge, the cause of each patient's dyspnea was determined by independent review of the entire medical record. The diagnostic accuracy of the different approaches was then compared. RESULTS: The study enrolled 1,005 patients. The LUS-implemented approach had a significantly higher accuracy (sensitivity, 97% [95% CI, 95%-98.3%]; specificity, 97.4% [95% CI, 95.7%-98.6%]) in differentiating ADHF from noncardiac causes of acute dyspnea than the initial clinical workup (sensitivity, 85.3% [95% CI, 81.8%-88.4%]; specificity, 90% [95% CI, 87.2%-92.4%]), chest radiography alone (sensitivity, 69.5% [95% CI, 65.1%-73.7%]; specificity, 82.1% [95% CI, 78.6%-85.2%]), and natriuretic peptides (sensitivity, 85% [95% CI, 80.3%-89%]; specificity, 61.7% [95% CI, 54.6%-68.3%]; n = 486). Net reclassification index of the LUS-implemented approach compared with standard workup was 19.1%. CONCLUSIONS: The implementation of LUS with the clinical evaluation may improve accuracy of ADHF diagnosis in patients presenting to the ED. TRIAL REGISTRY: Clinicaltrials.gov; No.: NCT01287429; URL: www.clinicaltrials.gov.

Dried plasma/blood spots for monitoring antiretroviral treatment efficacy and pharmacokinetics: a cross-sectional study in rural Burundi.

AIMS: In limited resource settings monitoring antiretroviral (ARV) treatment efficacy is restrained by the lack of access to technological equipment. The aim of the study was to assess the use of dried plasma (DPS) and blood spots (DBS) to facilitate ARV monitoring in remote settings where clinical monitoring is the primary strategy. METHODS: A cross-sectional study in HIV-positive ARV-treated patients in Kiremba, Burundi was performed. DBS were used for HIV-1 viral load (limit of the assay 250 copies ml(-1)) and genotypic drug resistance tests and dried plasma spots were used for concentration measurements. RESULTS: Three hundred and seven patients [201 female (88.6%), 14 children (4.5%)] were enrolled. HIV-1 viral load was <250, 250-1000 and >1000 copies ml(-1) in 250 (81.7%), 33 (10.8%) and 23 patients (7.5%). Eleven samples out of 23 were successfully amplified revealing nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistance associated mutations [in seven (58.3%) and six patients (50%)]. Nevirapine trough concentrations were <3000 ng ml(-1) in 28/189 patients (14.8%) and efavirenz 12 h concentrations were <1000 ng ml(-1) in 2/16 patients (12.5%). Children and patients with nevirapine exposure <3000 ng ml(-1) presented a higher risk of viral replication. CONCLUSIONS: Viral loads <250 copies ml(-1) were observed in 81.7% of patients (83.6% adults and 42.9% children). Children and patients with low nevirapine concentrations had higher risk of viral replication. Dried blood and plasma spots may be useful for monitoring HIV-positive patients including viral load and drug level measurement as part of treatment management in remote areas.

Pharmacokinetics of caspofungin increased dosage in a patient on rifampin-containing anti-tubercular treatment.

We describe a patient treated with caspofungin and rifampin; after increasing the dosage of the former (70 mg/day) we observed an unexpectedly lower plasma exposure (AUC0-24 79.5 µg/ml*h vs. 108.8 µg/ml*h). Although rifampin-mediated complete enzyme induction may take longer than 2 weeks, the clinical advantage of an increased caspofungin dose deserves clinical investigation.

Influence of CYP2B6 and ABCB1 SNPs on nevirapine plasma concentrations in Burundese HIV-positive patients using dried sample spot devices.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • Nevirapine pharmacokinetics are affected by several factors including CYP2B6 single nucleotide polymorphisms (SNPs). These genetic profiles are more common in African patients and they affect the drug clearance being associated with higher trough concentrations. Pharmacokinetic/pharmacogenetic (PK/PG) studies are difficult to perform in remote areas where refrigeration is not available, although dried plasma and dried blood methods have been validated. WHAT THIS STUDY ADDS: • Dried plasma spots are useful tools for studying nevirapine PK with a good association to plasma concentrations and they can be used in rural areas since a cold chain is not necessary. Dried blood spots can be used to store and analyze patients' DNA for PG polymorphisms. Nevirapine trough concentrations in Burundese patients, not studied so far, are above the target concentration (3000 ng ml(-1) ) in 84% of patients. CYP2B6 (both at position 516 and 983) but not ABCB1 (3435 and 1236) SNPs as well as age correlate with higher nevirapine exposure. AIMS: The pharmacokinetics (PK) and pharmacogenetics (PG) of nevirapine have been studied in rich and limited-resource countries. CYP2B6 single nucleotide polymorphisms (SNPs) have been associated with decreased drug clearance. We evaluated the PG determinants of nevirapine trough concentrations in a rural cohort in Burundi using easy to store and transport dried sample spot devices. METHODS: A cross-sectional analysis in HIV-positive nevirapine-treated patients in Kiremba, north of Burundi, was performed in 2009. After blood withdrawal whole blood was stored on dried blood spots and plasma (after centrifugation) was placed on dried plasma spot devices and stored at room temperature. Nevirapine plasma and dried sample spot concentrations were compared to test the clinical usefulness of this method. SNPs in CYP2B6 and ABCB1 (using a real time PCR technique) were analyzed and associated with nevirapine plasma trough concentrations. RESULTS: Nevirapine concentrations measured on dried plasma spot devices were highly related to plasma concentrations in 60 patients, although a negative bias was observed (-18%). Nevirapine trough concentrations were above the target concentration (3000 ng ml(-1) ) in 84% of patients and they were associated with CYP2B6 SNPs (both at position 516 and 983). No effect of ABCB1 SNPs was noted. CONCLUSIONS: Dried plasma spot devices are accurate tools for measuring nevirapine concentrations in rural settings where refrigeration is not available, despite a moderate underestimation bias. They allowed the evaluation of nevirapine concentrations in a cohort of HIV-infected people in rural Burundi, confirming very good exposure and correlation with PG polymorphisms in the CYP2B6 encoding gene.