Daptomycin Dosing Based on Ideal Body Weight versus Actual Body Weight: Comparison of Clinical Outcomes

Abstract

dDaptomycin use at our institution changed to ideal body weight dosing based on a published analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. Patients were treated for documented Enterococcus species, Staphylococcus aureus, or coagulase-negative Staphylococcus infections, including bloodstream, intraabdominal, skin and soft tissue, urinary, and bone. There was no statistically significant difference in clinical success between the groups (88.9% for actual body weight compared to 89.1% for ideal body weight, P ‫؍‬ 0.97). After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups. Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all patients and types of infections and organisms. C onventional daptomycin doses, based on actual body weight (ABW), result in sufficient drug exposure to meet an effective area under the curve (AUC)-to-MIC ratio. Dvorchik and Damphousse demonstrated that a single dose of 4 mg of daptomycin/kg of body weight administered to nonobese patients resulted in an AUC of 418 Ϯ 25 g · h/ml (1). A 6-mg/kg dose resulted in AUC values of 726 Ϯ 79 g · h/ml in healthy, nonobese patients (2). In a mouse thigh infection model, Safdar et al. determined that the 24-h AUC/MIC parameters associated with bacteriostatic effect were 388 to 537 for four ATCC Staphylococcus aureus strains and 0.94 to 1.67 for two clinical isolates of Enterococcus faecium (3).Pharmacokinetic parameters may change in some patient populations, including the obese population. In two studies evaluating ABW-dosed daptomycin pharmacokinetics in the morbidly obese (1, 4), the AUC increased 30 to 60% compared to in normalweight individuals. Volume of distribution (V) and clearance (CL) were reduced when normalized for weight.Daptomycin dosing can be limited by toxicity, especially myositis and creatine phosphokinase (CPK) elevations with exposures exceeding 2 weeks of duration (5). In an examination of data from a randomized trial of daptomycin treatment of bacteremia and endocarditis, a direct relationship between minimum serum concentration (C min ) and incidence of CPK elevation was established. Patients weighing Ն111 kg had a significantly higher probability of elevated C min than patients weighing Ͻ111 kg. Using a Monte Carlo evaluation, d...

Comprehensive Guidance for Antibiotic Dosing in Obese Adults

“…Monte Carlo simulations of 6 mg/kg dosing based on ABW 0.4 produced AUC values closest to that of nonobese patients and those seen in bacteremia and endocarditis clinical trials . In a retrospective analysis of patients with enterococcal and staphylococcal infections, no difference was reported in outcomes with dosing based on IBW or TBW, despite adjustment for age, sex, BMI, infection type, and organism type . A more recent observational study showed that dosing by ABW provides similar clinical, microbiological, and safety outcomes compared with TBW in obese patients…”

“…73 In a retrospective analysis of patients with enterococcal and staphylococcal infections, no difference was reported in outcomes with dosing based on IBW or TBW, despite adjustment for age, sex, BMI, infection type, and organism type. 74 A more recent observational study showed that dosing by ABW provides similar clinical, microbiological, and safety outcomes compared with TBW in obese patients. 75 Clinicians should be cognizant of daptomycin's dose-dependent musculoskeletal toxicity.…”

Treatment of bacterial infections in obese adult patients: how to appropriately manage antimicrobial dosage

“…The PK-PD characteristics of daptomycin suggest that a 500 mg or 750 mg fixed dose approach is plausible [33][34][35]. 6 mg/kg [36]. If 10 mg/kg were applied based on IBW then doses of approximately 455-776 mg would be computed that matches the aforementioned fixed-dose expectations [33][34][35].…”

Significant publications on infectious diseases pharmacotherapy in 2014

“…53 Am J Health-Syst Pharm-Vol 72 Aug 15, 2015 In July 2010, the University of Wisconsin Hospital and Clinics in Madison converted to daptomycin dosing using ideal body weight (IBW) based on analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. In order to describe their experience and compare clinical outcomes between ABW and IBW dosing of daptomycin, Ng et al 11 conducted a retrospective cohort study of patients treated with daptomycin between July 2009 and July 2011, using a preintervention and postintervention analysis. Adult patients with a positive culture who were treated with daptomycin for at least 72 hours were eligible for inclusion.…”

“…This study also provides important data regarding the need to carefully select patients who will likely benefit from therapy. 11 Daptomycin is a cyclic lipopeptide antibiotic approved by FDA for the treatment of skin and soft structure infections and S. aureus bacteremia, including right-sided endocarditis. According to the package labeling, daptomycin should be dosed based on actual body weight (ABW); no dosage adjustment is warranted for overweight or obese patients.…”