Laurie Barclay, MD

July 24, 2008

July 24, 2008 — Daptomycin was effective for skin and skin structure infections (SSSI), with similar outcomes for methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S aureus (MSSA), according to the results of a study reported at the 2008 Annual Conference on Antimicrobial Resistance, held in Bethesda, Maryland.

"MRSA is frequently identified as a contributor to clinical failure and increased hospitalization costs for SSSI and other infections compared to MSSA," author and presenter Kenneth Lamp, PharmD, senior director of Registry Research for Cubist Pharmaceuticals, Inc, in Lexington, Massachusetts, told Medscape Infectious Diseases. "It is unclear if these effects are a direct effect of MRSA as a pathogen or whether treatment differences between MRSA and MSSA also have an effect on outcomes. Since daptomycin has equivalent activity for MRSA and MSSA, we sought to examine the outcomes after daptomycin treatment for patients infected with MRSA or MSSA reported to a retrospective registry."

The Cubicin Outcomes Registry and Experience 2005 to 2006 was used to identify patients with only SSSI in which S aureus was the primary pathogen. Of 486 patients identified, 52 (11%) were not able to be evaluated for outcome and were excluded. At completion of daptomycin therapy, outcome was evaluated, with success defined as cure or improvement.

Of 434 evaluable patients, 338 (78%) had MRSA and 96 (22%) had MSSA. Compared with patients with MSSA, those with MRSA had lower incidence of diabetes (28% vs 41%; P = .02), fewer patients with MRSA were on dialysis when daptomycin was started (1.5% vs 7.3%; P = .008), and patients with MRSA had a higher incidence of uncomplicated SSSI (29% vs 18%; P = 0.04). These characteristics did not affect clinical outcomes.

Most patients achieved clinical success with daptomycin therapy (96% of patients with MRSA and 95% of patients with MSSA; P =.5). In 95 patients (22%), daptomycin was started as first-line therapy. Vancomycin was the most frequently prescribed prior antibiotic therapy (MRSA, 46%; MSSA, 45%); about one third of patients were switched to daptomycin because of vancomycin failure.

Patients with MRSA and MSSA were similar in terms of median daptomycin dose (MRSA: 4 mg/kg [56%], range, 2.9 – 10 mg/kg; MSSA: 4 mg/kg [59%], range, 3 – 8.5 mg/kg), median daptomycin duration (MRSA: 13 days, range, 1 – 243; MSSA, 11 days; range, 1 – 64 days; P = .4), and adverse events possibly related to daptomycin (MRSA: 18 [5%]; MSSA: 9 [9%]).

"In this set of patients, methicillin resistance did not appear to have an impact on the clinical success rates at the end of daptomycin therapy," Dr. Lamp said.

Scott Micek, PharmD, a clinical pharmacist at Barnes-Jewish Hospital in St. Louis, Missouri, was not involved with this study but reviewed it for Medscape Infectious Diseases.

"One third of patients initially treated with vancomycin had therapeutic failure," Dr. Micek said. "This is potentially of great significance, given [that] vancomycin remains the primary agent used to treat MRSA infections."

Dr. Lamp is an employee and stock holder of Cubist Pharmaceuticals, Inc, which manufactures daptomycin. Dr. Micek receives research grant support from Ortho-McNeil, Pfizer, Astra-Zeneca, and Astellas.

2008 Annual Conference on Antimicrobial Resistance: Abstract P9. June 23–25, 2008.