ABSTRACT
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ABSTRACT
INTRODUCTION: Daptomycin doses 8-12 mg/kg are recommended for susceptible dose-dependent Enterococcus species. However, data remain limited on safety outcomes of such dosing, compared to standard 4-6 mg/kg dosing. METHODS: In this retrospective cohort study, patients were stratified into daptomycin standard-dose (≤ 6.5 mg/kg) versus high-dose (≥ 7.5 mg/kg) groups. The primary outcome was daptomycin safety based on a composite of creatine kinase elevation, daptomycin-related peripheral blood eosinophilia, eosinophilic pneumonitis, alanine aminotransferase elevation, and alkaline phosphatase elevation. A secondary aim was to identify risk factors for daptomycin adverse effects. Inclusion criteria were age ≥ 18 years old, daptomycin receipt for ≥ 48 h, and Enterococcus cultures with a daptomycin minimal inhibitory concentration 2-4 mg/L. RESULTS: A total of 119 patients were included for analysis. Median daptomycin doses were 6.0 mg/kg (IQR 5.4, 6.1) and 8.1 mg/kg (IQR 7.9, 9.6) in the standard- and high-dose cohorts, respectively. Median durations were 13.5 days (standard-dose) and 16 days (high-dose) (p = 0.02). The composite safety endpoint occurred in 32.0% of the standard-dose group and 32.5% of the high-dose group (p = 0.96). Daptomycin was dose-reduced or held in 8.1% of patients experiencing an adverse effect. Concurrent antihistamine usage was associated with the composite outcome; however, there was no association with daptomycin dose or concurrent statin use. CONCLUSION: High-dose daptomycin was not associated with increased laboratory abnormalities or adverse drug reactions compared to standard-dose daptomycin.
ABSTRACT
Infective endocarditis (IE) is a rare but increasingly prevalent disease with high morbidity and mortality, requiring antimicrobials and at times surgical intervention. Through the decades of healthcare professionals' experience with managing IE, certain dogmas and uncertainties have arisen around its pharmacotherapy. The introduction of new antimicrobials and novel combinations are exciting developments but also further complicate IE treatment choices. In this review, we provide and evaluate the relevant evidence focused around contemporary debates in IE treatment pharmacotherapy, including beta-lactam choice in MSSA IE, combination therapies (aminoglycosides, ceftaroline), the use of oral antimicrobials, the role of rifamycins, and long-acting lipoglycopeptides.
ABSTRACT
BACKGROUND: In 2018, the Clinical Microbiology Laboratory at our institution adopted updated daptomycin Enterococcus-susceptible dose-dependent breakpoints. While the introduction of susceptible dose-dependent (SDD) was intended to guide practice toward optimal dosing, the understanding and application of daptomycin SDD breakpoints for enterococci were unknown. METHODS: This mixed-methods study combined a clinician survey with a retrospective pre-post prescribing analysis. An 8-question survey was distributed to infectious diseases (ID) and internal medicine (IM) clinicians. A retrospective chart review of hospitalized adults with infections due to Enterococcus spp. was conducted before (pre-SDD) and after (post-SDD) adoption of SDD reporting for enterococci. RESULTS: Survey response rates were 40 of 98 (41%) for IM and 22 of 34 (65%) for ID clinicians. ID clinicians scored significantly higher than IM clinicians in knowledge of SDD. Chart review of 474 patients (225 pre- vs 249 post-SDD) showed that daptomycin dosage following susceptibility testing was significantly higher post-SDD compared with pre-SDD (8.5 mg/kg vs 6.4 mg/kg; Pâ <â .001) with no difference in empiric dosing (6.3 mg/kg vs 6.2 mg/kg; Pâ =â .67). Definitive daptomycin use varied between the pre- and post-SDD periods (35.1% vs 16.9%; Pâ <â .001). CONCLUSIONS: The survey revealed that ID clinicians placed more importance on and had more confidence in the SDD category over IM clinicians. SDD reporting was associated with a change in definitive daptomycin dosing. ID specialist involvement is recommended in the care of infections due to enterococci for which daptomycin is reported as SDD given their expertise.
