Impact of prolonged carbapenem use-focused antimicrobial stewardship on antimicrobial consumption and factors affecting acceptance of recommendations: a quasi-experimental study.

This study aimed to assess the impact of a prolonged carbapenem use-focused antimicrobial stewardship program (ASP) on antimicrobial consumption and clinical outcomes and to analyze factors affecting adherence to interventions. Patients prescribed carbapenems for ≥ 2 weeks received intervention. Interrupted time-series analysis was performed to compare antimicrobial consumption before and after intervention. Factors associated with non-adherence to intervention were investigated. Of 273 patients who were eligible for intervention, discontinuation or de-escalation was recommended in 256 (94.1%) and intervention was accepted in 136 (53.1%) patients. Before intervention, carbapenem consumption significantly increased to 1.14 days of therapy (DOT)/1000 patient days (PD)/month (P = 0.018). However, it significantly declined by - 2.01 DOT/1000 PD/month without an increase in other antibiotic consumption (P < 0.001). Factors affecting non-adherence to intervention were younger age (odds ratio [OR] = 0.98; 95% confidence interval [CI] 0.96-1.00), solid organ malignancy (OR = 2.53, 95% CI 1.16-5.50), and pneumonia (OR = 2.59, 95% CI 1.08-6.17). However, ASP intervention was not associated with clinical outcomes such as length of hospital stay or mortality. Prolonged carbapenem prescription-focused ASP significantly reduced carbapenem consumption without adverse outcomes. Non-adherence to interventions was attributed more to prescriber-related factors, such as attitude, than patient-related factors including clinical severity.

Impact of Area Under the Concentration-Time Curve-Guided Monitoring on Vancomycin Nephrotoxicity and Treatment Outcomes in Methicillin-Resistant Staphylococcus Aureus Bacteremia in Korean Patients.

Background: Current guidelines for the therapeutic monitoring of vancomycin recommend dosing based on the area under the concentration-time curve (AUC) to achieve clinical efficacy while reducing nephrotoxicity. Although a wide range of nephrotoxicity thresholds have been reported, few studies have documented clinical outcomes based on AUC-guided vancomycin dosing in Korea. Objective: The aim of the study was to evaluate whether a relationship exists between AUC and treatment outcomes in vancomycin treated patients in methicillin-resistant Staphylococcus aureus bacteremia. Furthermore, this study tries to estimate AUC threshold for treatment failure and nephrotoxicity. Methods: The records of adult patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin for ≥72 hours without dialysis between April 2013 and April 2021, were reviewed retrospectively. Treatment success was defined as defervescence and blood culture sterilization by day 7. Nephrotoxicity was defined as an increase in serum creatinine levels ≥0.3 mg/dL or a 50% increase from baseline on 2 consecutive days. Bayesian estimation was used to predict individual vancomycin AUC. Both classification and regression tree and receiver operating characteristic curve analyses were performed to estimate the optimal AUC thresholds for vancomycin efficacy and nephrotoxicity. Results: Of 118 patients, 61 (51.7%) experienced treatment failure and 42 (35.6%) developed acute kidney injury. The vancomycin AUC threshold for predicting acute kidney injury was 615.0 mg· hr/L. In the multivariate analysis, AUC ≥615.0 mg· hr/L was a significant risk factor for nephrotoxicity (adjusted odds ratio [aOR] = 5.24; 95% CI, 1.8-14.65). The lower threshold for treatment failure was not defined because it was not statistically significant. Risk factors for treatment failure included low body mass index (aOR = 0.82; 95% CI, 0.70-0.96), severity of acute illness represented by complicated infection (aOR = 77.56; 95% CI, 16.7-359.4) and comorbidities, such as solid organ tumors (aOR = 6.61; 95% CI, 1.19-36.81) and cerebrovascular disease (aOR = 6.05; 95% CI, 1.17-31.23). Conclusions: Although AUC-guided vancomycin dosing was associated with a reduced risk of acute kidney injury, its ability to predict clinical outcomes was modest. Further studies are needed to define the AUC therapeutic range to maximize efficacy and minimize nephrotoxicity. (Curr Ther Res Clin Exp. 2023; 83:XXX-XXX).

Potential Impact of the Involvement of Clinical Pharmacists in Antimicrobial Stewardship Programs on the Incidence of Antimicrobial-Related Adverse Events in Hospitalized Patients: A Multicenter Retrospective Study.

Although specialized pharmacists have been suggested to be essential members of antimicrobial stewardship programs (ASPs), not all hospitals in Korea operate ASPs with pharmacists involved. We aimed to evaluate the association of involvement of clinical pharmacists as team members of multidisciplinary ASPs with the incidence of antimicrobial-related adverse drug events (ADEs). Five tertiary teaching hospitals participated in this retrospective cohort study. At each participating hospital, we randomly selected 1000 participants among patients who had received systemic antimicrobial agents for more than one day during the first quarter of 2017. We investigated five categories of antimicrobial-related ADEs: allergic reactions, hematologic toxicity, nephrotoxicity, hepatotoxicity, and antimicrobial-related diarrhea. Multivariate logistic regression analysis was used to evaluate the potential impact of pharmacist involvement in ASPs on the incidence of ADEs. A total of 1195 antimicrobial-related ADEs occurred in 618 (12.4%) of the 4995 patients included in the analysis. The overall rate of ADE occurrence was 17.4 per 1000 patient days. Hospitals operating ASPs with pharmacists showed significantly lower AE incidence proportions than other hospitals (8.9% vs. 14.7%; p < 0.001). Multidisciplinary ASPs that included clinical pharmacists reduced the risk of antimicrobial-related ADEs by 38% (adjusted odds ratio 0.62; 95% confidence interval 0.50-0.77). Our results suggest that the active involvement of clinical pharmacists in multidisciplinary ASPs may contribute to reduce the incidence of antimicrobial-related ADEs in hospitalized patients.