201. Safety and Effectiveness of Daily vs. Every Other Day Dosing of Daptomycin in Patients with Renal Insufficiency

Abstract

BackgroundDaptomycin administered at 48-hour (q48h) intervals is recommended in patients with renal impairment. Our institution utilizes daily dosing (q24h) of daptomycin in patients with renal impairment to theoretically optimize the area under the curve (AUC) in each 24-hour interval. However, the safety and effectiveness of this approach are unknown.MethodsThis retrospective descriptive analysis evaluated outcomes of comparable daptomycin dosing schemes administered q24h vs. q48h in patients with renal impairment (estimated creatinine clearance < 30 mL/minute). Inpatient adults ≥18 years old were included if they had at least one creatinine phosphokinase (CPK) obtained during admission and received either a q24h or q48h renally-adjusted daptomycin dose from May 2014 through December 2018. High-dose daptomycin therapy was defined as >3 mg/kg q24h or >6 mg/kg q48h. The primary outcome was difference in CPK elevations in the q24h vs. q48h dosing groups. Secondary outcomes included clinical and microbiological response, mortality, and hospital length of stay.ResultsThirty-seven patients met inclusion criteria [23 (62%) q24h vs. 14 (38%) q48h]. Median treatment duration was 5 (7 vs. 4) days. Twenty-two (59%) patients had enterococcal infections [17 (73%) q24h vs. 5 (35%) q48h]. Twenty-two (59%) patients received high-dose daptomycin therapy [18 (82%) vs. 4 (18%)]. Nine patients [7 (19%) vs. 2 (5%)] received a statin during daptomycin therapy. One (3%) patient developed a CPK elevation (statin and q24h group). No daptomycin dose was discontinued due to CPK elevation, or rhabdomyolysis. Median hospital length of stay was 10 days in both dosing groups. Clinical response [9 (64%) vs. 16 (69%)] and microbiological response [9 (64%) vs. 15 (65%)] were similar between the two dosing groups. However, 30-day mortality [5 (35%) vs. 4 (17%)] and 90-day mortality [6 (42%) vs. 5 (21%)] were higher in the q48h dosing group. The difference in effectiveness outcomes was greatest in the subset of patients with enterococcal infections (Table 1).ConclusionA daily daptomycin dosing strategy in patients with renal insufficiency was well tolerated and may be associated with improved effectiveness outcomes, particularly for enterococcal infections. Additional investigations of this approach are warranted. Disclosures All authors: No reported disclosures.