High prevalence of fluoroquinolone-resistant UTI among US emergency department patients diagnosed with urinary tract infection, 2018-2020.

BACKGROUND: Uropathogen resistance, fluoroquinolone-resistance (FQR), and extended spectrum beta-lactamase (ESBL), has been observed to be emerging worldwide with prevalences above recommended thresholds for routine empirical treatment. The primary aim of our study was to determine the prevalence of FQR from a geographically diverse sample of United States emergency departments (EDs). METHODS: We conducted a multi-center, observational cohort study using a network of 15 geographically diverse US EDs. All patients ≥18 years of age with the primary or secondary diagnosis of urinary tract infection (UTI) in the ED identified using International Classification of Diseases (ICD-10) diagnosis code of cystitis, pyelonephritis, or UTI from 2018 to 2020 were included. We calculated descriptive statistics for uropathogens and susceptibilities. Logistic regression analysis was used to identify antimicrobial resistance risk factors associated with FQR Escherichia coli. RESULTS: Among 3779 patients who met inclusion criteria, median age was 62.9 years (interquartile range [IQR]: 41-77.6) and 76.3% were female. The most common diagnoses were complicated (41.2%) and uncomplicated cystitis (40.3%). E. coli was the most common pathogen (63.2%), followed by Klebsiella pneumoniae (13.2%) and Enterococcus species (5.8%). Across all sites, overall E. coli FQ-resistance prevalence was 22.1%, ranging from 10.5 to 29.7% by site. The prevalence of ESBL-producing uropathogen was 7.4%, ranging from 3.6% to 11.6% by site. Previous IV or oral antimicrobial use in the past 90-days and history of a multi-drug resistant pathogen were associated with FQ-resistant E. coli (odds ratio [OR] 2.68, 95% confidence interval [CI]: 2.04-3.51, and OR 6.93, 95% CI: 4.95-9.70, respectively). Of the patients who had FQ-resistant E. coli or an ESBL-producing uropathogen isolated, 116 (37.1%) and 61 (36.7%) did not have any documented risk factors for resistance. CONCLUSION: FQ-resistant E. coli is widely prevalent across US sites highlighting the need for ongoing monitoring of antimicrobial resistance and, at some locations, modification of empirical treatments.

A Phase 2 Randomized Placebo-Controlled Adjuvant Trial of GI-4000, a Recombinant Yeast Expressing Mutated RAS Proteins in Patients with Resected Pancreas Cancer.

Purpose: GI-4000, a series of recombinant yeast expressing four different mutated RAS proteins, was evaluated in subjects with resected ras-mutated pancreas cancer. Methods: Subjects (n = 176) received GI-4000 or placebo plus gemcitabine. Subjects' tumors were genotyped to identify which matched GI-4000 product to administer. Immune responses were measured by interferon-γ (IFNγ) ELISpot assay and by regulatory T cell (Treg) frequencies on treatment. Pretreatment plasma was retrospectively analyzed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry for proteomic signatures predictive of GI-4000 responsiveness. Results: GI-4000 was well tolerated, with comparable safety findings between treatment groups. The GI-4000 group showed a similar pattern of median recurrence-free and overall survival (OS) compared with placebo. For the prospectively defined and stratified R1 resection subgroup, there was a trend in 1 year OS (72% vs. 56%), an improvement in OS (523.5 vs. 443.5 days [hazard ratio (HR) = 1.06 [confidence interval (CI): 0.53-2.13], p = 0.872), and increased frequency of immune responders (40% vs. 8%; p = 0.062) for GI-4000 versus placebo and a 159-day improvement in OS for R1 GI-4000 immune responders versus placebo (p = 0.810). For R0 resection subjects, no increases in IFNγ responses in GI-4000-treated subjects were observed. A higher frequency of R0/R1 subjects with a reduction in Tregs (CD4+/CD45RA+/Foxp3low) was observed in GI-4000-treated subjects versus placebo (p = 0.033). A proteomic signature was identified that predicted response to GI-4000/gemcitabine regardless of resection status. Conclusion: These results justify continued investigation of GI-4000 in studies stratified for likely responders or in combination with immune check-point inhibitors or other immunomodulators, which may provide optimal reactivation of antitumor immunity. ClinicalTrials.gov Number: NCT00300950.

Ethylene glycol and methanol ingestion cared for by tele-emergency pharmacy and tele-emergency medicine.

We believe this is the first documented case of a critically ill patient managed by telepharmacy in a remote, rural critical access hospital. We outline the case and the benefits of telepharmacy in under-resourced, rural critical access emergency departments.

Phase II study of the GI-4000 KRAS vaccine after curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, or G12V mutation.

INTRODUCTION: Patients with early-stage lung cancer have a high risk of recurrence despite multimodality therapy. KRAS-mutant lung adenocarcinomas are the largest genetically defined subgroup, representing 25% of patients. GI-4000 is a heat-killed recombinant Saccharomyces cerevisiae yeast-derived vaccine expressing mutant KRAS proteins. The present phase II study assessed the feasibility, immunogenicity, and safety of the GI-4000 vaccine in patients with early-stage, KRAS-mutant lung cancer. MATERIALS AND METHODS: Patients with stage I-III KRAS-mutant lung cancer who completed curative therapy were enrolled. The patients received the genotype matched GI-4000 vaccine for ≤ 3 years or until intolerance, disease recurrence, or death. The KRAS antigen T-cell response was assessed using the interferon-gamma enzyme-linked immunospot assay in peripheral blood mononuclear cells. The study was powered to detect an immune response in ≥ 25% of patients. RESULTS: A total of 24 patients were enrolled over 28 months. No vaccine-related serious adverse events occurred. One patient withdrew consent because of pain at the injection site. The study met its primary endpoint, with 50% of patients developing an immune response to mutant KRAS. The median number of vaccinations received was 15 (range, 1-19). Ten patients experienced disease recurrence, and 6 died. Compared with the genotypically matched historical controls, the recurrence rates were equivalent but overall survival showed a favorable trend. CONCLUSION: GI-4000 was well tolerated and immunogenic when used as consolidation therapy in patients with stage I-III KRAS-mutant lung cancer. The patterns of recurrence and death observed in the present study can be used to design a randomized study of GI-4000 with overall survival as the primary endpoint.