Daptomycin Use in Cancer Patients with Neutropenia.
Authors: Rolston Kenneth V.I. , McConnell Scott A. , Brown Jack , Lamp Kenneth C. 
Published: October 2019

Abstract
Infections occurring during neutropenia in cancer patients (pts) frequently involve Gram-positive pathogens and are complicated by antibiotic resistance. Outcomes for infections due to either methicillin-resistant or -susceptible Staphylococcus aureus (MRSA, MSSA) treated with vancomycin are considered suboptimal by many clinicians (Sakoulas G. J Clin Microbiol2004;42:2398–402). New effective agents are needed for treatment. Data were collected retrospectively as part of an ongoing registry (Cubicin Outcomes Registry and Experience; CORE, 2005 and 2006 program years). Data were collected on demographic and microbiologic characteristics; prior, concomitant and follow-up antibiotics; DAP regimen; and clinical data. Outcomes were assessed at the end of DAP therapy by the investigator who, in most cases, was the infectious disease physician 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 (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. Pts reported with neutropenia during DAP, a history of cancer, and evaluable for outcome (cure, improved, failure) were analyzed. Eighty-four pts had a history of cancer and had neutropenia during DAP treatment, of these, 72 (86%) were evaluable for DAP outcome. Sixty-five of 72 (90%) pts had either cure (n=40, 56%) or improved (n=25, 35%) as an outcome. Success rates (cure plus improved) stratified by the lowest WBC during DAP were; 29/34 (85%) for < 100 cells/m3, 26/28 (93%) for 100–499 cells/m3, and 10/10 (100%) for 500–1000 cells/m3, P=0.32. The median (range) time to clinical response in those successfully treated (data reported in 47 pts) was 4 days (1–21). Fifty-nine of 72 (82%) had a hematological malignancy. Fifty-eight percent were male, 22% were ≥66 yrs old, 7% had an initial CrCl <30 mL/min, 18% received DAP in an ICU. Eighty-eight percent of pts received antibiotics before DAP, most frequently with vancomycin (83%), cefepime (17%), and linezolid (16%). The most frequent reason for switching to DAP was prior clinical failure / resistance (54%). The major infections being treated with DAP were bacteremia (76%), UTI / pyelonephritis (10%), and uncomplicated skin and skin structure (6%). Seventy-four percent of pts with a WBC < 100 cells/m3 had a bacteremia. The most common Gram-positive pathogens reported were vancomycin-resistant enterococci (52%), coagulase-negative staphylococci (21%), and S. aureus (14%; 7/11, 64% were MRSA). The median (range) initial DAP dose was 6.0 mg/kg (3–7). The median (range) DAP duration of therapy was 13 days (1–86). Nineteen percent of the pts received DAP as an outpatient at some time during their therapy. There were 37 adverse events (AE) reported in 20 (28%) pts; however, only three AEs in 3 pts (4%) were assessed as possibly related to DAP. The data from the registry provide useful information about the clinical characteristics of neutropenic cancer patients treated with DAP for primarily bacteremia. Most of the pts were bacteremic and there was no difference in outcome regardless of the degree of neutropenia. These data require confirmation via prospective clinical trials.