Daptomycin Therapy Not Influenced by Renal Function in Patients With MRSA Bacteremia

SAN FRANCISCO, CA—Renal impairment of any kind had no significant impact on the efficacy of daptomycin compared with vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, a study presented at IDWeek 2013 has found.

Additionally, daptomycin activity was not affected by glomerular filtration rate (GFR).

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Concerns were raised about the efficacy of daptomycin for MRSA bloodstream infections in patients with impaired renal function (CrCl <50mL/min) after a recent FDA package insert change with additional warnings. This prompted Adam Weston, MD, from Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, and colleagues to conduct a retrospective cohort study of patients with MRSA bacteremia treated at a tertiary hospital from 2001–2011 who received ≥3 consecutive days of either vancomycin or daptomycin.

In a 2:1 ratio, propensity score matching was used to control for bias by indication to receive daptomycin. After matching, multivariable logistic regression was used to assess the outcome of treatment failure, a composite of in-hospital mortality, persistent bacteremia, or recurrence in vancomycin- vs. daptomycin-treated subjects and the interaction with renal function.

The average age of the study patients was 61 years; 60% were men. Patients in the vancomycin group received vancomycin for an average of 21 days, with a first vancomycin level of 16.7 on average drawn after a mean of 2 days. In the daptomycin group, patients received an average of 28 days of treatment after a mean of 7 days of prior therapy. The average dose of daptomycin was 6.8mg/kg (range 5.1–10.8mg/kg).

After analyzing 150 patients (vancomycin, n=100; daptomycin, n=50), 51 (51%) patients treated with vancomycin and 27 (58%) patients treated with daptomycin had a GFR <50 mL/min/1.73m2 (P=0.42). In a multivariable model, daptomycin therapy in patients with either a GFR >50 mL/min/1.73m2 (OR 0.45, 95% CI 0.11–1.79) or a GFR of <50 mL/min/1.73m2 (OR 0.46, 95% CI 0.11–1.94) was not significantly associated with treatment failure compared to vancomycin therapy.

Additionally, there was no significant interaction between the two agents (P=0.54), “indicating that any differences in treatment effect were not significant,” Dr. Weston noted. “Similar nonsignificant results were seen for the individual outcomes of mortality, persistent bacteremia, and recurrence.”

Neither daptomycin usage nor any stage of chronic kidney disease was significantly associated with failure, and no significant interaction between any stage of kidney disease and daptomycin usage was observed.

“As the usage of daptomycin for MRSA bloodstream infections and the prevalence of kidney disease continue to increase, physicians may be reassured by this data,” Dr. Weston said. “While this is the first study to evaluate this question, further nonrandomized prospective or larger retrospective studies may be needed to provide additional reassurance to clinicians.”

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