IMPORTANCE: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is ...unknown. OBJECTIVE: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. MAIN OUTCOMES AND MEASURES: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. RESULTS: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 interquartile range, 46-66 years; 227 39% women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. CONCLUSIONS AND RELEVANCE: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04292730
Background
We described the real‐life epidemiology and causes of infections on the different therapy phases in patients undergoing chimeric antigen receptor (CAR) T‐cells directed towards CD19+ or ...BCMA+ cells.
Methods
All consecutive patients receiving CAR T‐cell therapy at our institution were prospectively followed‐up. We performed various comparative analyses of all patients and subgroups with and without infections.
Results
Ninety‐one adults mainly received CAR T‐cell therapy for acute leukaemia (53%) and lymphoma (33%). We documented a total of 77 infections in 47 (52%) patients, 37 (48%) during the initial neutropenic phase and 40 (52%) during the non‐neutropenic phase. Infections during the neutropenic phase were mainly due to bacterial (29, 78%): catheter infections (11 38% cases), endogenous source (5 17%), and Clostridioides difficile (5 17%). Patients receiving corticosteroids after CAR T‐cell therapy had a higher risk of endogenous infection (100% vs. 16%; p = .006). During the non‐neutropenic phase, bacterial infections remained very frequent (24, 60%), mainly with catheter source (8, 33%). Respiratory tract infections were common (17, 43%).
Conclusions
Infections after CAR T‐cell therapy were frequent. During the neutropenic phase, it is essential to prevent nosocomial infections and balance the use of antibiotics to lower endogenous bacteraemia and Clostridial infection rates.
Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and ...based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.
Background: The direct identification of uropathogens from urine samples, in combination with the rapid detection of resistance, would allow early adjustment of empirical antimicrobial treatment. ...Methods: Two hundred and ninety-eight urine samples processed between 1 June and 31 December 2020, selected with flow cytometry, with direct identification by MALDI-TOF mass spectrometry, and rapid detection of extended-spectrum beta-lactamase (ESBL) and carbapenemases-producing strains by lateral flow were analyzed. Results: The positive predictive value of the direct identification of the 86 samples that met the flow cytometry criterion (>5000 bacteria/µL) was 96.4%. Reliable direct identification was obtained in 14 of the 27 (51.8%) urinary source bacteraemias. There was 100% agreement between the lateral flow and antibiogram in the detection of ESBL and carbapenemases. Conclusion: the protocol for the direct identification and rapid detection of ESBL and carbapenemases-producing strains from urine samples is a reliable and useful tool.
Pseudomonas aeruginosa is characterized by an important intrinsic resistance to antibiotics and it possess an extraordinary ability to develop resistance to nearly all available antimicrobials ...through selection of mutations. We review some of the pharmacodynamic principles of antibiotics predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment for empirical and directed treatment of P. aeruginosa invasive infections.
Abstract
Staphylococcus aureus is a major human pathogen causing a vast array of infections with significant mortality. Its versatile physiology enables it to adapt to various environments. Specific ...physiological changes are thought to underlie the frequent failure of antimicrobial therapy despite susceptibility in standard microbiological assays. Bacteria capable of surviving high antibiotic concentrations despite having a genetically susceptible background are described as ‘antibiotic tolerant’. In this review, we put current knowledge on environmental triggers and molecular mechanisms of increased antibiotic survival of S. aureus into its clinical context. We discuss animal and clinical evidence of its significance and outline strategies to overcome infections with antibiotic-tolerant S. aureus.
Ivermectin has recently shown efficacy against SARS-CoV-2 in-vitro. We retrospectively reviewed severe COVID-19 patients receiving standard doses of ivermectin and we compared clinical and ...microbiological outcomes with a similar group of patients not receiving ivermectin. No differences were found between groups. We recommend the evaluation of high-doses of ivermectin in randomized trials against SARS-CoV-2.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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