Pharmacy & Therapeutics - May 2008 - (Page 282) DRUG UTILIZATION EVALUATION Prescribing Trends with Daptomycin (Cubicin) For the Treatment of Gram-Positive Infections Noreen H. Chan Tompkins, PharmD, and Stephen J. Harnicar, PharmD INTRODUCTION Daptomycin (Cubicin for Injection, Cubist) is a cyclic lipopeptide derived from the fermentation of Streptomyces roseosporus. It has in vitro spectrum of activity against grampositive aerobic organisms, such as Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium. Daptomycin binds to bacterial membranes and causes a rapid depolarization of membrane potential. As a consequence, this inhibition of protein, DNA, and RNA synthesis results in bacterial cell death.1 At the time of our evaluation, daptomycin at a dose of 4 mg/kg per day was approved by the Food and Drug Administration (FDA) for infections caused by complicated skin and skin structure infections resulting from S. aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, and E. faecalis (vancomycin-susceptible isolates). The therapeutic use of daptomycin in treating bacteremia, endocarditis, and other severe infections caused by methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) remained under investigation by the FDA. In June 2004, daptomycin was officially added to the formulary at our hospital along with guidelines for its use. In addition to the guidelines, the use of daptomycin was permitted only after it was approved by the Antimicrobial Management Team and after consultation with an infectious-disease specialist. The P&T committee recommended a follow-up audit of annual usage. The hospital’s 2004 guidelines can be summarized as follows: Daptomycin is indicated for: • treatment of resistant gram-positive infection (e.g., MRSA or VRE) in patients who are allergic to vancomycin (Vancocin, Lilly) or linezolid (Zyvox, Pfizer). • treatment of resistant gram-positive infection (e.g., MRSA or VRE) that is resistant to vancomycin and linezolid. • treatment of resistant gram-positive infection (e.g., MRSA or VRE) in patients who develop thrombocytopenia considered to be secondary to linezolid use or in patients with existing thrombocytopenia if linezolid use is a concern; clinical judgment must be used. Daptomycin should not be used for: treatment of pneumonia, surgical prophylaxis, or empirical coverage. STUDY OBJECTIVES Our primary objective was to determine whether daptomycin use met the P&T committee’s approved guidelines. Secondary objectives were: • to determine the number of patients who had received previous therapy with vancomycin, linezolid, or quinupristin/dalfopristin (Synercid, Monarch) before switching to daptomycin. • to describe the infection and the organism for which daptomycin was prescribed. • to describe the daptomycin dosage regimen, including doses based on milligrams per kilogram of body weight. • to determine whether the dosage interval was appropriate for patients according to their renal function status. METHODS We performed a retrospective descriptive chart review after obtaining approval from the institutional review board. We identified patients for inclusion via a computerized report generated for all patients who had received daptomycin between December 2003 and December 2004. After the chart review was completed, the data were collated in a Microsoft Access database and analyzed in Epi Info. We also generated a computerized report to compare antibiotic usage trends for daptomycin, linezolid, and parenteral vancomycin. We depicted antibiotic measurement on the basis of the World Health Organization’s definition of defined daily doses (DDDs).2 RESULTS Daptomycin was prescribed for 44 patients during the study period. The mean ± standard deviation (SD) age was 58.6 ± 16.5 years (range, 22–90 years); 22 patients were men, and 22 were women. Forty-one patients (93.2%) were white, two patients (4.5%) were African-American, and one patient (2.3%) was Hispanic. The mean ± SD length of stay was 27.4 ± 26.4 days (range, 1–120 days; median, 17.5 days). Of the 44 patients, 32 (72.7%) met the drug usage guidelines and three (6.8%) did not; nine (20.5%) did not meet the specific guidelines, but we considered this to be clinically appropriate. Of the 32 cases for which the guidelines were appropriate, 15 cases were for the treatment of resistant gram-positive infections in patients who were allergic to vancomycin or linDisclosure: Since 2005, Dr.Tompkins has been the principal investigator at Allegheny General Hospital for the Cubicin Outcomes Registry and Experience (CORE) for the treatment of serious grampositive infections protocol, sponsored by Cubist Pharmaceuticals. Dr. Tompkins is a Clinical Specialist in Infectious Diseases at Allegheny General Hospital’s Department of Pharmacy in Pittsburgh, Pennsylvania. At the time of this project, Dr. Harnicar was a Pharmacy Technician at Allegheny General Hospital. He is currently an Oncology Pharmacy Resident at Memorial Sloan-Kettering Cancer Center in New York, New York. Accepted for publication January 31, 2008. 282 P&T® • May 2008 • Vol. 33 No. 5
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