Abstract

ObjectiveWe conducted a retrospective study based on composite endpoints for treatment failure to evaluate the effect of pharmacist-led VCM initial dose planning for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia patients.MethodsA retrospective cohort study was performed between pharmacist intervention and non-intervention groups. In this study, four types of failure were defined as the composite endpoint. When any one of the following failures occurred: 1) Death within 30 days from the start of VCM therapy, 2) Positive blood culture 7 days after the start of VCM therapy, 3) Change of VCM to another anti-MRSA agent, and 4) Development of nephrotoxicity, we considered that VCM treatment had failed. Survival time analysis was conducted with the Kaplan-Meier method and Cox’s proportional hazard model that included seven predefined parameters: pharmacist intervention, age, sex, weight, baseline VCM trough concentration, Charlson Comorbidity Index (CCI), and Pitt Bacteremia score (PBS). The effect of pharmacist intervention was studied as the survival probability estimated from the period of time from the start of VCM administration to the earliest failure.ResultsThe survival rate at 30 days after starting VCM therapy, at the end of follow-up, was 53.1 and 82.1% in the non-intervention and intervention groups, respectively. A significant survival time prolongation was noted in the intervention group (p = 0.011, log rank test). Among the seven parameters, only pharmacist intervention was significantly different and its hazard ratio was 0.26 (p = 0.014). The survival probability of the intervention group was higher than that of the non-intervention group for the time to each failure. In subgroup analyses, a significant difference was noted in male patients between the intervention and non-intervention groups (p = 0.005). Age was categorized into those under and over 65 years old. For those over 65 years old, a significant difference was shown between the groups (p = 0.018).ConclusionTo our knowledge, this is the first study to evaluate the failure of VCM treatment based on the composite endpoint. Pharmacist intervention through the initial VCM dose planning could maintain a balance between the efficacy and safety of VCM treatment and might avoid treatment failure for patients with MRSA bacteremia. Further investigations with large sample sizes are required to confirm our findings.

Highlights

  • Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a severe nosocomial infection that has been reported to be associated with a longer hospital stay, higher mortality, and increased costs [1,2,3]

  • Previous studies on the pharmacokinetics and pharmacodynamics (PK/PD) of VCM showed that a ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC) of !400 is optimal for clinical effectiveness [5]

  • It remains unclear whether pharmacist intervention is associated with a better clinical outcome and improved safety in patients with complicated MRSA infection resulting from the appropriate VCM trough concentration

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Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a severe nosocomial infection that has been reported to be associated with a longer hospital stay, higher mortality, and increased costs [1,2,3]. Some studies have demonstrated that VCM dose planning by pharmacists could lead to a higher percentage of patients with an optimal VCM trough concentration [11,12,13]. It remains unclear whether pharmacist intervention is associated with a better clinical outcome and improved safety in patients with complicated MRSA infection resulting from the appropriate VCM trough concentration. We conducted a retrospective study for the purpose of evaluating the effect of pharmacist-led VCM initial dose planning for MRSA bacteremia patients

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