Optimal Duration of Daptomycin plus Ceftaroline Combination Therapy in Persistent MRSA Bacteremia
Aliese Dashiell, Brandon Bookstaver, Ryan McCormick, Alex Ewing, Lauren McAbee, Jake Crocker
Background: Daptomycin and ceftaroline combination therapy (combination therapy) has been used as a salvage treatment of persistent methicillin-resistant S. aureus (MRSA) bacteremia for its synergistic effect, with promising clinical data when compared with monotherapy. The ideal duration of combination therapy is currently unclear.
Methods: A retrospective, multi-hospital healthcare system, observational cohort study comparing adult patients with persistent MRSA bacteremia that cleared blood cultures while receiving daptomycin and ceftaroline combination therapy. Patients were grouped into those who received ≤ 7 days of combination therapy after blood culture clearance (short duration group) and those who received > 7 days of combination therapy (long duration group). The primary outcome is a composite of 30-day all-cause mortality and recurrence of MRSA bacteremia. Secondary outcomes include adverse events, 90-day all-cause mortality, 90-day recurrence of MRSA bacteremia, and hospital length-of-stay.
Results: 94 patients were included, with 55 patients in the short duration group and 39 in the long duration group. Within the primary outcome, 10 patients in the short duration group and 7 patients in the long group experienced mortality or MRSA bacteremia recurrence within 30 days of the end of treatment (18.2% vs 18%, p=0.98). The short duration group experienced numerically more 90-day all-cause mortality events than the long duration group (29.1% vs 25.6%, p=0.71). There were similar rates of 90-day MRSA bacteremia recurrence between groups (3.7% vs 2.5%, p=1). The long duration group had a longer median overall hospital length-of-stay (LOS) (40 vs 22 days; p=0.002) and a longer median hospital LOS post-blood culture clearance (13.1 vs 34 days; p=0.001). There was no statistically significant difference in incidence of adverse events. The long duration group had numerically more instances of thrombocytopenia (5.5% vs 18%, p=0.09). Two cases of C. difficile requiring treatment occurred, both in the long duration group.
Conclusions: Among patients with persistent MRSA bacteremia, duration of combination therapy after blood culture clearance had no difference on 30-day mortality or recurrence. Results may help reduce unnecessary antibiotic exposure and hospital length-of-stay.
