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.

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.

Background: A penicillin allergy guidance document containing an algorithm for challenging penicillin allergic patients with β-lactams was developed by the antimicrobial stewardship program (ASP). As part of this algorithm, a “graded challenge” order set was created containing antimicrobial orders and safety medications along with monitoring instructions. The process is designed to challenge patients at low risk of reaction with infusions of 1% of the target dose, then 10%, and finally the full dose, each 30 minutes apart. We evaluated outcomes from the order set. Methods: Orders of the graded challenge over 17 months (March 2018 through July 2019) were reviewed retrospectively. Data were collected on ordering and outcomes of the challenges and allergy documentation. Use was evaluated based on ASP-recommended indications: history of IgE-mediated or unknown reaction plus (1) no previous β-lactam tolerance and the reaction occurred >10 years ago, or (2) previous β-lactam tolerance, now requiring a different β-lactam for treatment. Only administered challenges were included and descriptive statistics were utilized. Results: Of 67 orders, 57 graded challenges were administered to 56 patients. The most common allergies were penicillins (87.7%) and cephalosporins (38.6%), with the most common reactions being unknown (41.7%) or hives (22%). The most common antibiotics challenged were ceftriaxone (43.9%), cefepime (21.1%), and cefazolin (5.3%). Antibiotics given prior to challenge included vancomycin (48.2%), fluoroquinolones (35.7%), carbapenems (21.4%), aztreonam (19.6%), and clindamycin (12.5%). The median duration of challenged antibiotic was 6 days. The infectious diseases service was consulted on 59.6% of challenges and 75.4% of challenges were administered in non-ICU settings. There was 1 reaction (1.8%) involving a rash with the second infusion, which was treated with oral diphenhydramine and had no lasting effects. Based on indications, 80.7% of challenges were aligned with ASP guidance criteria. The most common use outside of these criteria was in patients without IgE-mediated reactions (10.5%). Most of these had minor rashes and could have received a full dose of a cephalosporin. Allergy information was updated in the electronic health record after 91.2% of challenges. Conclusions: We demonstrated the utility of a graded challenge process at our academic medical center. It was well tolerated, ordered frequently by noninfectious diseases clinicians, administered primarily in non-ICU settings, and regularly resulted in updated allergy information in the medical record. With many patients initially receiving broad-spectrum antibiotics with high costs or increased rates of adverse effects, graded challenges can potentially prevent the use of suboptimal therapies with minimal time and resource investment.Funding: NoneDisclosures: Scott Bergman reports a research grant from Merck.

Objective: We sought to determine the value of an audit-and-feedback monitoring method in facilitating meaningful practice changes to improve vancomycin dosing and monitoring. Design: Retrospective, multicenter, before-and-after implementation observational quality assurance initiative. Setting: The study was conducted in 7 not-for-profit, acute-care hospitals within a health system in southern Florida. Methods: The preimplementation period (September 1, 2019, through August 31, 2020) was compared to the postimplementation period (September 1, 2020, through May 31, 2022). All vancomycin serum-level results were screened for inclusion. The primary end point was the rate of fallout, defined as vancomycin serum level ≥25 µg/mL with acute kidney injury (AKI) and off-protocol dosing and monitoring. Secondary end points included the rate of fallout with respect to AKI severity, rate of vancomycin serum levels ≥25 µg/mL, and average number of serum-level evaluations per unique vancomycin patient. Results: In total, 27,611 vancomycin levels were analyzed from 13,910 unique patients. There were 2,209 vancomycin serum levels ≥25 µg/mL (8%) among 1,652 unique patients (11.9%). AKI was identified in 379 unique patients (23%) with a vancomycin levels ≥25 µg/mL. In total, 60 fallouts (35.2%) occurred in the 12-month preimplementation period (∼5 per month) and 41 fallouts (19.6%) occurred in the 21-month postimplementation period (∼2 per month; P = .0006). Failure was the most common AKI severity in both periods (risk: 35% vs 24.3%, P = .25; injury: 28.3% vs 19.5%, P = .30; failure: 36.7% vs 56%, P = .053). Overall, the number of evaluations of vancomycin serum levels per unique patient remained consistent throughout both periods (2 vs 2; P = .53). Conclusions: Implementation of a monthly quality assurance tool for elevated outlier vancomycin levels can improve dosing and monitoring practices resulting in enhanced patient safety.