Comparative renal risk of long-term use of beta-lactams in combination with vancomycin across the continuum of care.

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.

Comparison of Oral and Intravenous Definitive Antibiotic Therapy for Beta-Hemolytic Streptococcus Species Bloodstream Infections from Soft Tissue Sources: a Propensity Score-Matched Analysis.

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. We conducted a retrospective study of adults with beta-hemolytic streptococcal BSI from a primary skin/soft tissue source from 2015 to 2020. Patients transitioned to oral antibiotics within 7 days of treatment initiation were compared to those who continued intravenous therapy, after propensity score matching. The primary outcome was 30-day treatment failure (composite of mortality, infection relapse, and hospital readmission). A prespecified 10% noninferiority margin was used for the primary outcome. We identified 66 matched pairs of patients treated with oral and intravenous antibiotics as definitive therapy. Based on an absolute difference in 30-day treatment failure of 13.6% (95% confidence interval 2.4 to 24.8%), the noninferiority of oral therapy was not confirmed (P = 0.741); on the contrary, the superiority of intravenous antibiotics is suggested by this difference. Acute kidney injury occurred in two patients who received intravenous treatment and zero who received oral therapy. No patients experienced deep vein thrombosis or other vascular complications related to treatment. In patients treated for beta-hemolytic streptococcal BSI, those who transitioned to oral antibiotics by day 7 showed higher rates of 30-day treatment failure than propensity-matched patients. This difference may have been driven by underdosing of oral therapy. Further investigation into optimal antibiotic choice, route, and dosing for definitive therapy of BSI is needed.

Vancomycin AUC values estimated with trough-only data: Accuracy in an adult academic medical center population.

PURPOSE: Vancomycin 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: Accuracy 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.

Identification of priority targets for intervention in outpatient antimicrobial stewardship.

A multimodal antimicrobial stewardship intervention was associated with a decrease in antibiotic prescribing for targeted non-coronavirus disease 2019 (COVID-19) upper respiratory infections from 27.6% in 2019 to 7.6% in 2021. We describe our approach to prioritizing departments for 3 levels of interventions in the setting of limited stewardship personnel.