The devil's in the defaults: An interrupted time-series analysis of the impact of default duration elimination on exposure to fluoroquinolone therapy.

OBJECTIVE: To determine whether removal of default duration, embedded in electronic prescription (e-script), influenced antibiotic days of therapy. DESIGN: Interrupted time-series analysis. SETTING: The study was conducted across 2 community hospitals, 1 academic hospital, 3 emergency departments, and 86 ambulatory clinics. PATIENTS: Adults prescribed a fluoroquinolone with a duration <31 days. INTERVENTIONS: Removal of standard 10-day fluoroquinolone default duration and addition of literature-based duration guidance in the order entry on December 19, 2017. The study period included data for 12 months before and after the intervention. RESULTS: The study included 35,609 fluoroquinolone e-scripts from the preintervention period and 31,303 fluoroquinolone e-scripts from the postintervention period, accounting for 520,388 cumulative fluoroquinolone DOT. Mean durations before and after the intervention were 7.8 (SD, 4.3) and 7.7 (SD, 4.5), a nonsignificant change. E-scripts with a 10-day duration decreased prior to and after the default removal. The inpatient setting showed a significant 8% drop in 10-day e-scripts after default removal and a reduced median duration by 1 day; 10-day scripts declined nonsignificantly in ED and ambulatory settings. In the ambulatory settings, both 7- and 14-day e-script durations increased after default removal. CONCLUSION: Removal of default 10-day antibiotic durations did not affect overall mean duration but did shift patterns in prescribing, depending on practice setting. Stewardship interventions must be studied in the context of practice setting. Ambulatory stewardship efforts separate from inpatient programs are needed because interventions cannot be assumed to have similar effects.

Comparison of Open-Access, Trough-Only Online Calculators Versus Trapezoidal Method for Calculation of Vancomycin Area Under the Curve (AUC).

BACKGROUND: Vancomycin area-under-the-curve (AUC) monitoring is associated with reduced nephrotoxicity but may increase cost and workload for personnel compared to trough monitoring. OBJECTIVE: The purpose of this study was to compare the accuracy of vancomycin AUC calculated by open-access, online, trough-only calculators to AUCs calculated by the trapezoidal method (TM) using peak and trough concentrations. METHODS: This retrospective, multi-center study included adults ≥18 years old with stable renal function who received vancomycin with steady-state peak and trough concentrations. Areas under the curve calculated by TM were compared to AUCs calculated by 3 online calculators using trough-only options for calculation: ClinCalc, VancoVanco, and VancoPK. The primary outcome was actual difference in AUC between TM and the online calculators. Secondary outcomes were percent difference in AUC and clinical alignment in dose adjustments between methods. RESULTS: Seventy patients were included for analysis. There was a statistically significant difference in AUC between TM and ClinCalc (median actual difference: -52, P < 0.001) and VancoVanco (median actual difference: 95, P < 0.001), whereas there was no significant difference between TM and VancoPK (median actual difference: -0.8, P = 0.827). Discordant dose adjustments were indicated when comparing ClinCalc, VancoVanco, and VancoPK to TM in 28%, 36%, and 12% of cases, respectively. CONCLUSION: The AUC calculator most closely aligned with TM was VancoPK, whereas other included calculators were statistically different. Owing to the cost and complexity of obtaining multiple levels, our findings support using a single steady-state trough using VancoPK as an alternative to TM for calculation of vancomycin AUC.

Use of therapeutic drug monitoring to characterize cefepime-related neurotoxicity.

STUDY OBJECTIVES: Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime-related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN. DESIGN: This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM). Potential CRN cases were identified utilizing a standard definition. The primary outcomes of the study were to determine the incidence of CRN and evaluate the relationship between cefepime trough concentrations, the average daily AUC, and neurotoxicity. Bayesian posteriors were generated for each patient using a cefepime pharmacokinetic (PK) model, and the mean daily area under the concentration-time curve (AUC) was calculated. Multiple regression was performed to assess the association between CRN, cefepime PK, and clinical predictors of neurotoxicity. MAIN RESULTS: Four hundred eighty-one patients with 503 hospital encounters received cefepime TDM and were included in the analysis. The incidence of CRN was 4.4% (22/503). Patients with CRN had a higher incidence of renal dysfunction, hypertension, and diabetes mellitus compared to patients without CRN (non-NT). The mean cefepime trough concentration was significantly greater in the CRN patients than in the non-NT group (61.8 ± 33.7 vs. 30 ± 27.7 mg/L, respectively, p = 0.0002). Cefepime trough concentration and renal dysfunction were independently associated with increased risk of CRN in the adjusted multiple regression model. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CRN. Delaying cefepime TDM greater than 72 h after the initiation of cefepime was associated with a 3-fold increased risk of CRN. CONCLUSION: Cefepime should be used cautiously in hospitalized patients with renal dysfunction due to the risk of neurotoxicity. Dose optimization utilizing TDM early in cefepime treatment may minimize adverse effects and improve patient safety.