Impact of a monthly antimicrobial stewardship quality assurance tool for elevated vancomycin levels.

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.

Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam.

BACKGROUND: Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). METHODS: We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. RESULTS: We included VAN/C/T (n = 90) and VAN-TZP (n = 284) 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 = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). CONCLUSIONS: Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa.

BACKGROUND: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). METHODS: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 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 (NCOs) and was examined by multivariable logistic regression analysis (MLR). RESULTS: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (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 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). CONCLUSIONS: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs.