Background: Staphylococcus aureus remains a common cause of ventilatorassociated pneumonia, with little change in infection rates over the past 15 years. This phase 2 study evaluated suvratoxumab, an anti-alpha-toxin monoclonal antibody, in reducing incidence of S. aureus pneumonia in intensive care unit (ICU) subjects on mechanical ventilation (MV). Methods:We did a multicenter, single-dose, randomized, placebo-controlled, doubleblind, phase 2 pilot trial in 9 countries. Eligible subjects were patients in an ICU ≥18 years of age, currently intubated and on MV, positive for S. aureus lower respiratory tract (LRT) colonization as assessed by polymerase chain reaction (PCR) of endotracheal aspirate, and with no diagnosis of new-onset pneumonia. Subjects were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received anti-S. aureus antibiotics for >48 hours; had a CPIS ≥6, APACHE-II score ≥25, a SOFA score ≥9; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Subjects were screened for S. aureus lower respiratory tract (LRT) colonization using real-time polymerase chain reaction (PCR).Colonized subjects were randomly assigned 1:1:1 to a single intravenous infusion of suvratoxumab 2000 mg, 5000 mg or placebo. Randomization was stratified by country and by whether subjects received anti-S. aureus systemic antibiotic therapy. Based on pre-defined PK criteria, the 2000 mg arm was discontinued upon the recommendation of the data monitoring committee at an interim analysis. Primary efficacy endpoint was incidence of S. aureus pneumonia, adjudicated by a blinded independent panel, through 30 days post dose in the modified intent-to-treat study population. Primary safety endpoints were Francois et al. Suvratoxumab Ph2 (NCT02296320) D3 5 treatment-emergent AEs assessed through 30 and 90 days, treatment-emergent SAEs, adverse events of special interest, and new onset chronic disease, all assessed through 190 days. Findings: PCR screening of 737 ICU subjects identified 213 with S. aureus colonization; of these, 96 were randomized to receive suvratoxumab 5000 mg and 100 to placebo. At 30 days, 17/96 (17•7%) suvratoxumab and 26/100 (26•0%) placebo subjects had developed S. aureus pneumonia (relative risk reduction, 31.9%; 90% confidence interval [CI], −7•5 to 56•8; P = 0•166). At 30 days, incidences of treatmentemergent adverse events (AEs) and serious AEs were similar in suvratoxumab and placebo groups (90•6% [87/96] vs. 90•0% [90/100] and 37•5% [36/96] vs 32•0% [32/100], respectively). At 90 and 190 days, incidence of treatment-emergent AEs was still similar in suvratoxumab and placebo groups (92.

Background Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. Methods EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. Results Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: − 23.7%; 80% confidence interval [CI] − 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) μg/mL, with 80.6% (n = 58/72) subjects achieving concentrations > 1.7 μg/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups. Conclusions The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov (NCT02696902) on 11th February 2016 and on EudraCT (2015-001706-34) on 7th March 2016.

Este estudo tem por objetivo analisar o perfil epidemiológico da COVID-19 em Santa Catarina. Foram estudados os coeficientes de prevalência, incidência, mortalidade e letalidade, com base nos dados secundários fornecidos pela Secretaria de Estado da Saúde de Santa Catarina acerca da distribuição de casos confirmados da COVID-19 no período de 14 semanas (28 de fevereiro a 30 de maio de 2020), e segundo o sexo, a faixa etária e a macrorregião de referência. Os resultados apontam que as taxas de prevalência de casos ativos e incidência em Santa Catarina foram ascendentes, mas de tendência linear, diferentemente da curva exponencial verificada no Brasil, no mesmo período de tempo. Constatou-se uma maior prevalência de casos ativos entre as mulheres, mas um maior número de óbitos e maior taxa de letalidade entre os homens, em praticamente toda a série temporal considerada. As maiores prevalência e incidência da COVID-19 foram detectadas nas faixas entre 20-39 e 40-59 anos, grupos mais sujeitos à exposição e disseminação do vírus, e menor incidência foi detectada na população mais jovem (0-19 anos). A taxa de letalidade por faixa etária mostrou-se especialmente significativa entre os mais idosos. As macrorregiões do Grande Oeste e Foz do Rio Itajaí foram as que mais aportaram casos acumulados da COVID-19, tanto em termos de prevalência quanto de incidência. Novos estudos durante a após a pandemia devem avançar no entendimento da disseminação da doença em Santa Catarina e no Brasil.

Objective. This study aimed to summarize the accuracy of the different methods for detecting trigger asynchrony at the bedside in mechanically ventilated patients. Method. A systematic review was conducted from 1990 to 2020 in PubMed, Lilacs, Scopus, and ScienceDirect databases. The reference list of the identified studies, reviews, and meta-analyses was also manually searched for relevant studies. The reference standards were esophageal pressure catheter and/or electrical activity of the diaphragm. Studies were assessed following the QUADAS-2 recommendations, while the review was prepared according to the PRISMA criteria. Results. One thousand one hundred and eleven studies were selected, and four were eligible for analysis. Esophageal pressure was the predominant reference standard, while visual inspection and algorithms/software comprised index tests. The trigger asynchrony, ineffective expiratory effort, double triggering, and reverse triggering were analyzed. Sensitivity and specificity ranged from 65.2% to 99% and 80% to 100%, respectively. Positive predictive values reached 80.3 to 100%, while the negative predictive values reached 92 to 100%. Accuracy could not be calculated for most studies. Conclusion. Algorithms/software validated directly or indirectly using reference standards present high sensitivity and specificity, with a diagnostic power similar to visual inspection of experts.

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