Pharmacy & Therapeutics - May 2008 - (Page 283) Drug Utilization Evaluation: Daptomycin ezolid; 12 cases were for the treatment of resistant grampositive infections resistant to linezolid; and five cases were for the treatment of resistant gram-positive infections in patients who developed thrombocytopenia thought to be secondary to linezolid or in patients with existing thrombocytopenia if linezolid use was a concern. Of the three patients not meeting the guidelines, one patient was treated for an empyema, and two patients were treated empirically with daptomycin: one of these two patients had a urinary tract infection (UTI) and the other had sepsis with pneumonia. The patient with the UTI received one dose of daptomycin overnight. After a consultation with an infectiousdisease specialist the following day, daptomycin was discontinued. An infectious-disease consultation was obtained for all 44 patients, resulting in 100% compliance. Thirty-eight patients (86.4%) had previously been treated with vancomycin; 15 of these 38 patients (39.5%) were considered intolerant to vancomycin, as judged by the physician, at the time daptomycin was prescribed. The median length of vancomycin therapy before the initiation of daptomycin was 10 days (range, 1–28 days). Of the 38 patients, eight (21%) were considered by the physician to have an inadequate response to vancomycin. The median length of vancomycin therapy was 14 days (range, 5–42 days). Of the 44 patients, 24 (54.5%) had received linezolid previously. Of the 24 patients, eight (33.3%) were intolerant to linezolid at the time daptomycin was prescribed. The median length of linezolid therapy was four days (range, 2–14 days). Of the 24 patients, four (16.7%) were considered to have an inadequate response to linezolid. The median length of linezolid therapy was six days (range, 1–10 days). Other vancomycin and linezolid exposures included either (1) an earlier history of intolerance to vancomycin or linezolid or (2) another reason, such as a change from vancomycin because of a resistant organism (e.g., VRE). No patients had received quinupristin/dalfopristin earlier (Figure 1). Daptomycin was prescribed for bacteremia in 13 patients (29.5%); skin and skin structure infections in 10 (22.7%); osteomyelitis in four (9.1%); endocarditis in four (9.1%); foreignbody infection in four (9.1%); sepsis in five (11.4%); and other infections in four (9.1%). At the initiation of therapy, targeted organisms included MRSA in 18 patients (40.9%); VRE in 11 (25%); methicillinresistant Staphylococcus epidermidis (MRSE) in five (11.4%); and other infections in 10 (22.7%); the latter consisted of two cases each of methicillin-susceptible S. aureus [MSSA], methicillin-susceptible S. epidermidis [MSSE], a history of MRSA, 20 15 No. of cases 10 7 5 0 Vancomycin, n = 38, (86.4%) Linezolid, n = 24 (54.5%) Intolerant history Intolerant current case Inadequate clinical response Other 15 8 9 4 8 4 8 Figure 1 Previous gram-positive antibiotic exposure. None of the patients received quinupristin/dalfopristin. Enterococcus species, or empirical therapy with no positive culture identified. Of the 44 patients, eight had a second gram-positive organism of concern: VRE in three patients; Enterococcus species in two patients; and a history of MRSA, MSSE, or VRE in one patient each. The mean dosage was 336.8 ± 114.3 mg (range, 200–600 mg) or 4.4 ± 1.1 mg/kg (range, 1.9–6 mg/kg) (Table 1). The mean weight was 86.8 ± 24.8 kg (range, 45.4–150 kg). Daptomycin was prescribed every 24 hours for 34 patients (77.3%), every 48 hours for nine patients (20.5%); and after each hemodialysis for one patient (2.2%). The mean creatinine clearance (CrCl) ± SD was 54.6 ± 32.4 mL/minute (range, 4–129 mL/minute). We used the Cockcroft–Gault equation to calculate CrCl. Thirty-two patients (72.7%) had a CrCl of 30 mL/minute or more, and 12 patients (27.3%) had a CrCl of less than 30 mL/minute. Therefore, the initial dosage interval was appropriate for 42 patients (95.5%) and inappropriate for two patients (4.5%). In one patient with an inappropriate dosage interval, the dose was changed to the appropriate interval before the second dose was administered. The mean length of inpatient therapy was 6.9 ± 6.3 days (range, 1–28 days). The median was five days. Twenty-one patients (47.7%) were discharged home with daptomycin. The mean total length of therapy, including outpatient therapy, was 22.2 ± 18.3 days (range, 1–56 days). The median was 14 days. A baseline creatinine kinase (CK) was obtained for nine patients (20.9%), and all baseline values were within normal limits. Among patients whose CK levels were being monitored, no patients experienced increased CK concentrations during their hospitalization. Hypotension secondary to sepsis occurred in one patient who was receiving daptomycin. This patient had previously received vancomycin and rifampin for a nonhealing MRSA wound infection. Because of the potential reaction to daptomycin, the patient was subsequently switched to linezolid. The quarterly usage of IV vancomycin at baseline (July to September 2003) was 62.5 defined daily doses (DDDs) per Table 1 Daptomycin Dosage* Daptomycin Dose (mg/kg) Below 4 4 4.5–4.9 6 * Based on the patient’s total body weight. No. of Patients (%) 6 (14%) 23 (53.5%) 2 (4.6%) 12 (27.9%) Vol. 33 No. 5 • May 2008 • P&T® 283
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