Clinical Outcomes of Daptomycin for Vancomycin-resistant Enterococcus Bacteremia

Abstract

Purpose: In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicrobials in the treatment of VRE (faecium or faecalis) bacteremia from multiple centers across the United States.

Methods: Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant β-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive β-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs.

Findings: Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant β-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3-4 µg/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant β-lactam therapy (clinical success, 88% vs 79% for MIC ≤2 vs 3-4 µg/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced ≥1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients).

Implications: Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant β-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant β-lactams with daptomycin.

Keywords: MIC, enterococci; VRE bacteremia; daptomycin; enterococcus; β-lactam.