Daptomycin Use in Neutropenic Patients with Gram-Positive Bacteremia.
Authors: Rolston Kenneth VI , McConnell Scott A , Brown Jack , Lamp Kenneth C 
Published: April 2020

Abstract
Infections occurring during neutropenia frequently involve Gram-positive pathogens complicated by antibiotic resistance. Outcomes for infections due to gram-positive organisms treated with vancomycin are considered suboptimal by many clinicians. New effective agents are needed for treatment. Data were collected retrospectively as part of an ongoing registry (The Cubicin Outcomes Registry and Experience; CORE, 2006 and 2007 program years). Patients (pts) were enrolled into CORE randomly from all pts receiving daptomycin (DAP) at participating sites as long as they received at least one dose of DAP and were not participating in a clinical trial. Data was collected on demographic, microbiologic, prior, concomitant and follow-up antibiotics, DAP regimen, and clinical data. Outcomes were assessed at the end of DAP therapy by the investigators who in most cases were infectious disease physicians involved in the treatment of the patient. The definitions for clinical outcome were: Cure - clinical signs and symptoms resolved (and/or) no additional antibiotic therapy necessary (and/or) negative culture reported at the end of therapy; Improved - partial resolution of clinical signs and symptoms (and/or) additional antibiotic therapy warranted at the end of therapy; Failure - inadequate response to therapy: worsening or new/recurrent signs and symptoms (or) need for a change in antibiotic therapy (or) positive culture reported at the end of therapy; Nonevaluable - unable to determine response due to insufficient information. Pts reported with neutropenia during DAP, gram-positive bacteremia, and evaluable for outcome (cure, improved, failure) were analyzed for success; nonevaluable patients (12/115, 10%) were included in the safety analysis. One hundred and three neutropenic patients with gram-positive bacteremia had outcomes for DAP available. Ninety of 103 (87%) pts had either cure (n=53, 51%) or improved (n=37, 36%) as an outcome. Success rates (cure plus improved) by the lowest WBC during DAP were; 45/52 (87%) for ≤ 100 cells/m3, 30/36 (83%) for 101–499 cells/m3, and 15/15 (100%) for 500–1000 cells/m3, P=0.25. The median (range) time to clinical response in those successfully treated by the lowest WBC during DAP were (data reported in 60/90 pts); 4 days (1–21) for ≤ 100 cells/m3, 2 days (1–10) for 101–499 cells/m3, and 3 days (1–8) for 500–1000 cells/m3. Seventy-five of 103 (73%) had a hematological malignancy. Fifty-nine percent were male, 25% were ≥66 yrs old, 15% had an initial CrCl &lt;30 mL/min., 89% were located in a hospital 48 hours prior to DAP therapy, and 29% received DAP in an ICU. Twenty patients had DAP as first line therapy and 18/20 (90%) were successes. Eighty-one percent of pts received antibiotics before DAP treatment, most frequently with vancomycin (87%), linezolid (21%), and cefepime (15%). The most frequent reason for prior antibiotic discontinuation was prior clinical failure/resistance (49%). The most common pathogens reported were vancomycin-resistant enterococci (47%), coagulase-negative staphylococci (25%), and vancomycin-sensitive enterococci (11%). The median (range) initial DAP dose was 6.0 mg/kg (3–10). The median (range) DAP duration of therapy was 13 days (1–63). Sixteen percent of the pts received DAP as an outpatient at some time during their therapy. Seven of 115 patients (6%) experienced a possibly-related adverse event (AE). Overall, 8% (9/115) required DAP discontinuation. The data from the registry provide useful information about the clinical characteristics of patients with neutropenia and bacteremia treated with daptomycin. The degree of neutropenia did not affect success rates. These data require confirmation via prospective clinical trials.