Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.
Background We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of Gram-negative infections (GNI), primarily including carbapenem-resistant Enterobacterales (CRE). Methods This is a real-world, multi-center, retrospective cohort within the United States between 2017-2020. Adult patients who received MEV for ≥ 72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCO) and was examined by multivariable logistic regression analysis (MLR). Results Overall, 126 patients were evaluated from 13 medical centers within ten states. The most common infection source were respiratory tract (38.1%) and intraabdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in four patients; nephrotoxicity (n=2), hepatoxicity (n=1), and rash (n=1). CART-BP between early and delayed treatment was 48 hours (P=0.04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (aOR=0.277, [0.081 – 0.941]). Conclusion Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNI, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCO.
Introduction Although antimicrobial stewardship initiatives in the outpatient setting have been increasing, the effect of order set implementation on antibiotic prescribing for acute respiratory tract infections (ARTI) has not been fully established. Objective This study's objective was to determine the impact of order sets and education on antibiotic prescribing for ARTI in the outpatient setting. Methods This was a quasi‐experimental research study conducted from January 2015 through December 2016. The study was conducted at an adult ambulatory care clinic associated with a tertiary care medical center. Order sets and prescriber education were created and implemented to aid in the diagnosis and treatment of ARTI. The primary end point was a composite of antibiotic prescribing frequency for ARTI. Secondary objectives included antibiotic appropriateness, patients requiring follow‐up clinic visits, and development of Clostridioides difficile infection. Results A total of 3292 patients were included in the study. Unspecified respiratory tract infection (RTI) was the most common diagnosis. Antibiotic prescribing decreased from 33% to 24% in the postintervention period (relative risk 0.74 [0.64‐0.85], P = <.0005). Antibiotic appropriateness was increased in the postintervention period (70%‐85%, P = <.0005) and significant reductions in clinic revisits were observed in the postintervention group, from 2.3% to 0.2% (odds ratio 15.2 [3.6‐64.1], P = .0002). Conclusions Implementation of order sets and education to aid in the management of ARTI at an outpatient clinic resulted in an overall decrease in antibiotic prescribing, improvements in antibiotic appropriateness, and decreased 30‐day clinic revisits. Order sets and education should be considered as a part of a multimodal approach to outpatient antimicrobial stewardship.
432 Background: Novel agents that inhibit kinases in the hypoxia and MTOR pathways can achieve response rates of 30-60% in renal cell carcinoma (RCC); however, protein biomarkers to diagnose RCC and guide treatment have not been identified. Methods: We developed the use of two high-throughput, nanoscale immunoassays to profile hypoxia and downstream signaling in clinical specimens from patients with RCC. These automated technologies minimize errors due to manual variability, and make 96 independent measurements per overnight experiment. We used size-based protein separation (Sally Instrument, Protein Simple) to quantify proteins using antibody-specific detection, normalized to loading control. Next, we used a nano-immunoassay with charge-based separation (NIA, Nanopro1000 Instrument, Protein Simple) to distinguish multiple charged modifications of individual proteins, and measure relative ratios of individual unphosphorylated and phosphorylated isoforms. Results: We first optimized assays for proteins in MAPK, PI3K and STAT pathways, and loading controls, to analyze frozen surgical specimens and ex-vivo fine needle aspirates (FNA’s) performed immediately following nephrectomy. We analyzed more than 200 FNA’s from solid tumors, comparing RCC with paired adjacent non-tumor tissue, and other epithelial malignancies. Basal MAPK signaling of tumors varied across 3 logs of expression. Unique to NIA, we analyzed percent phosphorylation and resolved differences in single phosphorylations. Subtle differences in basal MAPK signaling between tumor calls and adjacent non-tumor tissue can distinguish RCC from other malignancies. Lastly, we prospectively collected and analyzed blood peripheral mononuclear cells from 20 RCC patients before and during treatment with standard targeted therapies. Kinase inhibitors can preferentially inhibit or activate specific protein phospho-isoforms. Conclusions: Our studies demonstrate that rapid and quantitative nanoproteomic profiling in very small amounts of clinical specimen may accelerate translational studies for novel diagnostic and predictive biomarkers.
Background Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactam (BL) such as piperacillin-tazobactam (TZP) but not had been evaluated with ceftolozane-tazobactam (C/T). We aim to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared to VAN in combination to TZP (VAN-TZP). Method We conducted a multi-center observational comparative study across the United States. The primary analysis was a composite outcome of AKI: 1) RIFLE, 2) AKIN, or 3) VAN-induced-nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis had been conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time-to-nephrotoxicity between the two groups. Results We included (n = 90) VAN/C/T and (n = 284) VAN-TZP at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs. 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = 0.011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with patients receiving VAN-C/T; with an aOR of 3.308 [1.560-6.993]. Results of the stratified Kaplan-Meir with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients receiving VAN-TZP (P = 0.004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = 0.001). Conclusions Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to the piperacillin which is a component in the VAN-TZP combination but not the VAN-C/T.
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