Pharmacy & Therapeutics - April 2008 - (Page 223) CLINICAL FOCUS Skin and Skin Structure Infections, And Control of Hemostasis during Surgery Walter Alexander Daptomycin Favored over Vancomycin For Skin Infections A study comparing the relative costs and clinical efficacy of treatment of complicated skin and skin structure infections (cSSSIs) with either daptomycin (Cubicin for Injection, Cubist Pharmaceuticals) or vancomycin (Vancocin, Eli Lilly/ViroPharma) found that a shorter duration of therapy tipped the balance in favor of daptomycin, the newer agent.1 Among patients whose infections resolved completely, the median duration of intravenous (IV) therapy was four days with daptomycin and seven days for vancomycin. Susan Davis, PharmD, Assistant Professor of Pharmacy at Wayne State University in Detroit, Michigan, and her colleagues noted that in 2004, according to the most recent surveys sponsored by the Centers for Disease Control and Prevention (CDC), SSSIs were the primary diagnosis in approximately 562,000 hospital discharges in the U.S., with an average length of stay of 4.7 days. Significant increases in cost of care have accompanied the growing prevalence of methicillinresistant Staphylococcus aureus (MRSA) infection in both hospital and community settings. Daptomycin, which was approved by the FDA in 2003, is a novel lipopeptide antibiotic indicated for treatment of cSSSIs caused by susceptible bacterial strains of gram-positive Streptococcus species and S. aureus, including MRSA. Speaking in a teleconference briefing coinciding with the publication of the study in Pharmacotherapy,1 senior investigator Michael Rybak, PharmD, MPH, Professor of Pharmacy and Director of AntiInfective Research at Wayne State University, said that the open-label study evaluated clinical and economic outcomes in an acute-care setting (Detroit Receiving Hospital, a level 1 trauma center) among patients admitted with these infections. Daptomycin-treated patients (n = 53) were compared with vancomycin-treated historical controls (n = 212) matched in a 1:4 ratio. Patients in the prospective arm received IV daptomycin 4 mg/kg every 24 hours for at least three days but for not more than 14 days. Controls received vancomycin for at least three days according to a dosing nomogram achieving trough concentrations of 5 to 20 mcg/mL (average, 13 mcg/mL). Additional treatment with aztreonam (Azactam, Elan), tobramycin (Tobradex, Alcon), or metronidazole (Flagyl, Pfizer) was permitted when gram-negative or anaerobic coverage was needed. After 72 hours, patients could be switched to oral antimicrobial regimens at the discretion of the primary physician. Similarly, patients could be switched to nafcillin (Unipen, Wyeth) if methicillin-susceptible S. aureus (MSSA) infection was identified. Both clinical and economic data were collected. Clinical The author is a freelance medical writer living in New York, New York. outcomes for these patients were determined by an investigator who was blinded to the treatment drug and to the suspected or cultured organism. S. aureus, the most common organism isolated in each group, was found in 51% of the daptomycin patients and in 79% of the vancomycin patients (P < 0.001). MRSA was also found more often in patients receiving vancomycin (75%) than in those receiving daptomycin (42%) (P < 0.001). The difference, Dr. Rybak explained in an interview, was that his hospital’s policy required vancomycin to be used only for MRSA or suspected MRSA. If patients had a streptococcal infection or an infection caused by MSSA, they were switched to a beta-lactam. In the prospective study, patients could continue with daptomycin if they had any type of gram-positive, streptococcal, staphylococcal, MRSA, or MSSA infection. Therefore, it is more likely that historical control patients receiving vancomycin would have had S. aureus infection, probably MRSA. Neither group experienced any antimicrobial-related adverse events or deaths. Although all patients in both groups achieved clinical success by the end of therapy, a significantly higher propor tion of patients who received daptomycin achieved clinical success by the third and fifth days. Furthermore, a significantly greater proportion of these patients (77%; n = 41) achieved clinical cure at the end of inpatient antimicrobial therapy, compared with the vancomycin patients (42%; n = 89) (P < 0.001). This association remained significant after the investigators controlled for the presence of MRSA, comorbidities, or surgical procedures related to infection management. The median duration to achieve clinical cure was three days shorter with daptomycin (four days; range, 2–10 days) compared with seven days with vancomycin (range, 3–19 days) (P < 0.001). Patients receiving daptomycin needed a shorter median duration of IV antimicrobial therapy (four days; range, 3–13 days) versus a median duration of seven days for vancomycin (range, 3–14 days) (P < 0.001). The antibiotic-related length of stay for the daptomycin patients was a median of four days (range, 3–13 days, and the median duration with vancomycin was eight days (range, 3–19 days) (P < 0.001). Clinically and molecularly defined community-associated MRSA was identified in 45 patients (15 receiving daptomycin; 30 receiving vancomycin). All of the patients achieved clinical success by the end of therapy, but the clinical success rate on the third day was higher with daptomycin (93% in 14 of 15 patients) than with vancomycin (57% in 17 of 30 patients) (P < 0.05). Costs for were higher for IV daptomycin (median, $666; range, $500–$1,660) than for vancomycin (median, $124; range, $23–$650). The difference between therapy with daptomycin and with vancomycin was reduced when all inpatient antimicrobials were taken into account (daptomycin, median $678; Vol. 33 No. 4 • April 2008 • P&T® 223
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