Preliminary, real-world, multicenter experience with omadacycline for Mycobacterium abscessus infections

Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen fo

The clinical impact of rapid respiratory virus testing in emergency departments: A systematic review and meta-analysis of randomized trials

Background: rapid tests for respiratory viruses, including multiplex panels, are increasingly available in Emergency Departments (ED). Their impact on patient outcomes remains unclear.Objectives: to determine if ED rapid respiratory virus testing in patients with suspected acute respiratory infection (ARI) decreases antibiotic use, ancillary tests, ED length of stay, ED return visits and hospitalization and increases influenza antiviral treatment.Data sources: we searched Ovid MEDLINE, Embase (Ovid), Scopus, and Web of Science from 1985 to November 14, 2022.Study selection: we included randomized controlled trials of patients of any age with ARI in an ED. The primary intervention was rapid viral testing.Extraction, data and synthesis: in this systematic review and meta-analysis, PRISMA reporting guidelines were followed. Two independent reviewers extracted data and assessed risk of bias using Cochrane’s Risk of Bias 2.0. Estimates were pooled using random-effects models. Quality of evidence was assessed using the GRADE framework.Main outcomes and measures: antibiotic use and secondary outcomes were pooled separately as risk ratio (RR) and risk difference estimates with 95% confidence intervals [CI]s.Results: of 7157 studies identified, 11 (n=6068 patients) were included in pooled analyses. Routine rapid viral testing did not impact antibiotic use (RR 0.99; 95% CI 0.93-1.05; high certainty) but was associated with higher use of influenza antivirals (RR 1.33; 95% CI 1.02-1.75; moderate certainty) and lower use of chest radiography (0.88; 95% CI 0.79-0.98; moderate certainty) and blood tests (RR 0.81; 95% CI 0.69-0.97; moderate certainty). There was no association with urine testing (RR 0.95; 95% CI 0.77-1.07; low certainty), ED length of stay (0h; 95% CI -0.17h-0.16h; moderate certainty), return visits (RR 0.93; 95% CI 0.79-1.08; moderate certainty) or hospitalization (RR 1.01; 95% CI 0.95-1.0 high certainty). Adults represented 16% of participants. There was no effect of viral testing on antibiotic use in any prespecified subgroup by age, test method, publication date, number of viral targets, risk of bias, and industry funding.Conclusions and relevance: available evidence shows limited benefits of routine viral testing in EDs for patients with ARI. Further studies in adults, especially those with high-risk conditions, are warranted

1082. Real-World Experience with Omadacycline for Nontuberculous Mycobacterial Infections: A Multicenter Evaluation

Background: Nontuberculous mycobacteria (NTM) are resistant to numerous antibiotics and lead to significant morbidity and mortality. Omadacycline (OMC) is an aminomethylcycline antibiotic that is Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Furthermore, OMC has shown in vitro activity against NTM. Given that real-world evidence is lacking, our primary objective was to evaluate the clinical success and tolerability of OMC when used for a variety of NTM infections. Methods: This was a multicenter, retrospective, observational study conducted from January 2020 to June 2021. We included all patients ≥ 18 years of age that received OMC of any indication for Mycobacterium spp. The primary outcome was clinical success, defined as a lack of all-cause mortality, lack of persistence or re-emergence of infection during or after therapy, and lack of alteration of OMC. Incidence of adverse effects potentially attributable to OMC and reasons for OMC utilization were also analyzed. Results: A total of 31 patients were included from 12 geographically distinct academic health systems (median age: 57 (IQR, 45-63) years; 45% male; 81% Caucasian). The majority of isolated pathogens were Mycobacterium abscessus complex (84%) and of those with subspeciation performed (54%), the majority (86%) were subsp. abscessus. The primary infections were of pulmonary origin (67%) and the median (IQR) duration of OMC therapy was 5.3 (3.2-9.4) months. Most isolates did not have OMC susceptibility conducted (87%), while the majority did for tigecycline (90%). Clinical success was reported in 81% of the population. Most patients were on combination antimicrobial therapy, and 39% of patients reported an adverse effect while on OMC (58% gastrointestinal distress). The majority of patients were prescribed OMC due to ease of administration (61%) and antimicrobial resistance to previous antibiotics (42%). Conclusion: OMC may be a potential option for the therapy of NTM infections. Prospective, randomized clinical trials are needed to confirm our preliminary findings

Clinical Outcomes of Eravacycline in Patients Treated Predominately for Carbapenem-Resistant Acinetobacter baumannii

Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE: Acinetobacter baumannii, particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii, where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49–67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4–14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75)

Template-induced macrocycle diversity through large ring-forming alkylations of tryptophan

Macrocyclic peptidomimetics are valuable in research and serve as lead compounds in drug discovery efforts. New methods to prepare such structures are of considerable interest. In this pilot study, we show that an organic template harboring a latent cinnamyl cation participates in novel Friedel-Crafts macrocyclization reactions with tryptophan. Upon joining the template to Trp-Trp-Tyr, a single operation efficiently generates eight unique macrocycles. Each has been isolated and thoroughly characterized. Product distribution as a function of Brønsted and/or Lewis acidic conditions was explored, and outcomes were compared to rearrangements induced within a corresponding tyrosine-linked cyclic ether. The solution structure of a new macrocyclic pyrroloindoline was solved using a combination of two-dimensional NMR methods and molecular mechanics simulations. Template-induced structural diversification of peptide sequences harboring aromatic residues has potential to create myriad macrocycles that target surfaces involved in protein-protein interactions