High-Dose Daptomycin an Alternative for Serious Gram-Positive Infections

SAN DIEGO, CA— Doses of daptomycin that are ≥10mg/kg may be a feasible option for the treatment of critical gram-positive infections, as reported at IDWeek 2012.

Gram-positive bacteria are a progressively widespread cause of nosocomial and community-acquired infections. At a 4mg/kg dose, daptomycin is indicated for the management of complicated skin and skin structure infections; at a 6mg/kg dose, daptomycin is indicated for S. aureus bacteremia, including right-sided endocarditis. Daptomycin doses of ≥8mg/kg were shown to be safe and effective when studied in patients with clinically significant gram-positive infections. Although not extensively tested, a small number of experts have utilized doses of ≥10mg/kg daptomycin to treat infections.

A retrospective data analysis performed by Dina Besece, PharmD, from Cubist Pharmaceuticals, Lexington, MA, included information obtained from the 2005–2009 program years of the Cubicin Outcomes Registry and Experience (CORE) multicenter registry. Safety was analyzed in patients receiving a ≥10mg/kg dosage of daptomycin. Efficacy was analyzed in patients with an evaluable outcome at the end of daptomycin therapy using protocol defined criteria. Success was deemed cure plus improved.

A total of 44 patients were identified, constituting 0.8% of CORE patients; of these patients, 38 (86%) were evaluable for efficacy.

The median daptomycin dose was 10mg/kg (minimum 10mg/kg, maximum 14.75mg/kg; 34% dosed >10mg/kg). The median duration of daptomycin treatment was 15 days (minimum 1 day, maximum 78 days).

Among evaluable patients, the clinical success rate was 81.8% (31 of 38 patients). Skin infections (32%) and bacteremia (26%) were the most common diagnoses; the most common pathogens included S. aureus (37%; 93% of which was MRSA) and Enterococcus species (26%; 60% vancomycin-resistant Enterococcus). For successfully treated patients (n=22), the median time to clinical response was 3.5 days (minimum 1 day, maximum 26 days).

Six of 44 patients in the safety analysis experienced one or more non-drug related serious adverse event. Dr. Besece and colleagues noted that three patients (7%) reported four possibly related adverse events, consisting of elevated creatine phosphokinase (n=3) and myopathy (n=1). Four patients (9%) discontinued daptomycin due to adverse events. “Daptomycin was rarely administered at doses >10mg/kg, but usage patterns, outcomes, and adverse events were consistent with prior analyses from this registry,” reported Dr. Neuner.