Ashley Barlow1, Emily L Heil1,2, Kimberly C Claeys3,4. 1. University of Maryland Medical Center, Baltimore, MD, USA. 2. University of Maryland School of Pharmacy, Baltimore, MD, USA. 3. University of Maryland Medical Center, Baltimore, MD, USA. kclaeys@rx.umaryland.edu. 4. University of Maryland School of Pharmacy, Baltimore, MD, USA. kclaeys@rx.umaryland.edu.
Abstract
INTRODUCTION: Vancomycin remains first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections (BSI); however, its toxicity and reported clinical failures are well established. Binary efficacy endpoints evaluating alternative anti-MRSA therapies leave clinicians deciphering between segregated clinical and safety outcomes and do not provide a comprehensive patient-centered picture of comparative therapies. This study aimed to apply a novel methodology, desirability of outcomes ranking (DOOR), to compare anti-MRSA therapies. METHODS: This was a single-centered, retrospective, cohort of adult patients with MRSA BSI that received vancomycin, daptomycin, or ceftaroline. A previously developed DOOR for S. aureus BSI was adjusted and applied to this cohort to compare vancomycin-treated versus daptomycin/ceftaroline-treated patients. The DOOR had five mutually exclusive ranks: (1) alive without treatment failure, infectious complications, or grade 4 adverse events (AEs); (2) alive with any one of treatment failure, infectious complications, or grade 4 AE; (3) alive with two of treatment failure, infectious complications, or grade 4 AE; (4) alive with all three treatment failure, infectious complications, or grade 4 AE; or (5) deceased. RESULTS: A total of 43 vancomycin-treated and 13 daptomycin/ceftaroline-treated patients were included. Baseline clinical characteristics were similar, except for higher median serum creatinine in the daptomycin/ceftaroline cohort (0.76 [IQR 0.57, 1.11] vs 1.36 [IQR 1.09, 1.91] mg/dL, P = 0.03). Patients in the daptomycin/ceftaroline cohort had a 92% probability of better outcome using DOOR methodology. Patients treated with daptomycin/ceftaroline experienced less MRSA BSI persistence (0% vs 13.9%), MRSA BSI recurrence (7.8% vs 25.6%), grade 4 AEs (23.1% vs 46.5%), and in-hospital mortality (0% vs 9.3%). CONCLUSIONS: Although limited by sample size, this study demonstrates the potential of DOOR to produce valuable, patient-centered results. Clinicians are encouraged to become familiar with appropriate use and interpretation of DOOR methodology as it will become an increasingly common endpoint in clinical trials.
INTRODUCTION:Vancomycin remains first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections (BSI); however, its toxicity and reported clinical failures are well established. Binary efficacy endpoints evaluating alternative anti-MRSA therapies leave clinicians deciphering between segregated clinical and safety outcomes and do not provide a comprehensive patient-centered picture of comparative therapies. This study aimed to apply a novel methodology, desirability of outcomes ranking (DOOR), to compare anti-MRSA therapies. METHODS: This was a single-centered, retrospective, cohort of adult patients with MRSA BSI that received vancomycin, daptomycin, or ceftaroline. A previously developed DOOR for S. aureus BSI was adjusted and applied to this cohort to compare vancomycin-treated versus daptomycin/ceftaroline-treated patients. The DOOR had five mutually exclusive ranks: (1) alive without treatment failure, infectious complications, or grade 4 adverse events (AEs); (2) alive with any one of treatment failure, infectious complications, or grade 4 AE; (3) alive with two of treatment failure, infectious complications, or grade 4 AE; (4) alive with all three treatment failure, infectious complications, or grade 4 AE; or (5) deceased. RESULTS: A total of 43 vancomycin-treated and 13 daptomycin/ceftaroline-treated patients were included. Baseline clinical characteristics were similar, except for higher median serum creatinine in the daptomycin/ceftaroline cohort (0.76 [IQR 0.57, 1.11] vs 1.36 [IQR 1.09, 1.91] mg/dL, P = 0.03). Patients in the daptomycin/ceftaroline cohort had a 92% probability of better outcome using DOOR methodology. Patients treated with daptomycin/ceftaroline experienced less MRSA BSI persistence (0% vs 13.9%), MRSA BSI recurrence (7.8% vs 25.6%), grade 4 AEs (23.1% vs 46.5%), and in-hospital mortality (0% vs 9.3%). CONCLUSIONS: Although limited by sample size, this study demonstrates the potential of DOOR to produce valuable, patient-centered results. Clinicians are encouraged to become familiar with appropriate use and interpretation of DOOR methodology as it will become an increasingly common endpoint in clinical trials.
Entities:
Keywords:
Daptomycin; Desirability of outcomes ranking; S. aureus bacteremia; Vancomycin
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