Hannan, Kellie N. Arensman

Background: Data are controversial regarding nephrotoxicity risk with vancomycin plus piperacillin–tazobactam (VPT) compared to vancomycin alone or in combination with other beta-lactams (BLs) in acute care use. Furthermore, data are lacking on the incidence of acute kidney injury (AKI) with long-term use of VPT including outpatient parenteral antimicrobial therapy (OPAT). Methods: This retrospective study included 826 adult patients on an intravenous vancomycin plus BL for ⩾2 weeks, including cefepime, piperacillin/tazobactam, ertapenem, or meropenem, from August 2017 to January 2022. The primary outcome was incidence of AKI. Univariate and multivariable Cox proportional hazard regression analyses were conducted to adjust for confounding variables. A secondary analysis based on the propensity score (PS)-matched cohort was performed. Results: AKI occurred in 14.4% of patients in the VPT group ( n = 15/104) compared to 5.5% in the other BL group ( n = 40/722) ( p < 0.001). Average time to AKI from start of combination therapy was 9.4 (1.7–12.0) days in the VPT group and 10.9 (5–22.7) days in the other BL group ( p = 0.20). The median duration of vancomycin and BL in the overall cohort was approximately 1 month. Beyond BL selection, patient characteristics were not associated with AKI other than the receipt of concomitant acyclovir [hazard ratio (HR) 2.48 (95% confidence interval (CI): 1.33–4.65), p = 0.004]. In the PS-matched cohort, AKI occurred in 14.4% of patients in the VPT group ( n = 15/104) and 5.3% in the other BL group ( n = 11/208) ( p = 0.006). Receipt of VPT [HR: 2.55 (1.36–4.78), p = 0.004] and acyclovir [HR: 2.38 (1.19–4.74), p = 0.014) remained significantly associated with AKI in the multivariable model. Conclusion: Clinicians should exercise caution when using VPT for >2 weeks, including in the OPAT setting, even when no renal dysfunction is observed during the initial week of combination therapy.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.

AbstractPurposeVancomycin area under the concentration-time curve (AUC) can be calculated using steady-state serum peak and trough concentrations; however, compared to traditional trough-only monitoring, this approach requires an additional blood sample. Recently published data demonstrated vancomycin AUC estimations using trough-only data with a volume of distribution (Vd) model incorporating age and actual body weight were reasonably accurate and precise in a veteran population. This study sought to extend these methods to a Mayo Clinic adult population.MethodsA retrospective, observational cohort of adult patients with documented steady-state vancomycin peak and trough concentrations was evaluated. Vancomycin AUCs were estimated using trough-only data, and 4 Vd models were assessed for accuracy and precision. Estimated AUCs were compared to AUCs calculated using 1-compartment intermittent infusion equations and steady-state peak and trough (“peak-trough”) data.ResultsThe study population (N = 95) was 46% female, with a median age of 59 years and a median weight of 97 kg. Using the VancoPK equation Vd = 0.29 (age in y) + 0.33 (actual weight in kg) + 11, the mean peak-trough and estimated trough-only AUC were 533 and 534, respectively, with a correlation of 0.936. The root mean square error was 47.7, meaning about 95% of AUCs were within 95 mg · h/L of peak-trough AUCs.ConclusionsAccuracy and precision of Vancomycin AUC estimations using trough-only data and the described Vd model were demonstrated in a Mayo Clinic cohort. Targeting an estimated AUC of 500 mg · h/L using the VancoPK model would likely result in an actual AUC within 400 to 600 mg · h/L.

Abstract Background URIs are the most common indication for outpatient antibiotic prescribing. Given high rates of unnecessary prescribing, these indications have been identified as a high-priority target for outpatient antimicrobial stewardship programs (ASP). Our primary objective was to evaluate the impact of a system-wide, multifaceted, outpatient ASP intervention bundle on unnecessary antibiotic prescribing for URI. Methods This quasi-experimental study was conducted from 2019 to 2021. ICD-10 codes for URIs were grouped into 3 tiers (i.e., tier I = antibiotics always indicated, tier II = sometimes, tier III = never). Encounters from 5 care specialties (i.e., family medicine, community internal medicine, express care, pediatrics, and emergency department) with a tier III URI primary ICD-10 code but without a secondary tier I or tier II code were included. COVID-19 ICD-10 codes were excluded. Interventions included construction of a prescribing data model, dissemination of clinician prescribing data and education, promotion of symptom management strategies, a patient-facing commitment poster, and a pre-populated URI order panel. Tools were designed at a system level and implemented by regional champions beginning in the 3rd quarter of 2020. The primary outcome was the rate of antibiotic prescribing, and the secondary outcome and counterbalance measure was the rate of repeat URI-related healthcare contact within 14 days. Outcomes were analyzed with chi-square with an α level of 0.05. Results A total of 147403 encounters were included. The overall antibiotic prescribing rate decreased from 24.1% to 12.3% between 2019 and 2021 (p&lt; 0.01). Significant reductions in tier III antibiotic prescribing were demonstrated for each region, care specialty, and syndrome evaluated (Table 1). A reduction in repeat healthcare contact was seen across the total cohort (9.5% in 2019 vs. 8.3% in 2021, p&lt; 0.01); decreases in repeat contact rates were observed in those not initially receiving an antibiotic (10.3% vs. 8.6%, p&lt; 0.01), but not in those who initially received an antibiotic (6.8% vs. 6.8%, p = 0.94). Tier III URI encounter level antimicrobial prescribing rates by region, care specialty, and syndrome Conclusion A multifaceted, outpatient ASP intervention bundle decreased rates of unnecessary antimicrobial prescribing without increasing rates of 14-day repeat URI-related healthcare contact. Disclosures Paschalis Vergidis, MD, AbbVie: DSMB|Cidara: Grant/Research Support|Scynexis: Grant/Research Support Evan Draper, PharmD, Gilead Foundation: Grant/Research Support Sara Ausman, PharmD, Gilead: Honoraria Christina G. Rivera, PharmD, Gilead: Grant/Research Support|Gilead: Honoraria|Insmed: Honoraria.