Retrospective Evaluation of Daptomycin, a Lipopeptide Antibiotic, in Bone Marrow Transplant and Hematology/Oncology Patients.

Abstract

Background: Daptomycin is a lipopeptide antibiotic with potent activity against many Gram-positive organisms. Efficacy in immunocompromised patients is unknown because these patients have been excluded from daptomycin premarketing studies. Methods: Patients with documented infections treated at the University of Michigan Health System in either the bone marrow transplant or hematology/oncology service were identified in the Cubicin® Outcomes Registry and Experience (COREsm 2004 and 2005). Demographic, disease state, clinical, and microbiologic data were collected. Clinical outcomes were assessed using the following definitions: Cure - clinical signs and symptoms are resolved and/or no additional antibiotic therapy is necessary or infection cleared with a negative culture reported at the end of daptomycin therapy; Improved - partial resolution of clinical signs and symptoms and/or additional antibiotic therapy is necessary at the end of daptomycin therapy; Failure - inadequate response to therapy or resistant, worsening or new/recurrent signs and symptoms, or the need for a change in antibiotic therapy or a positive culture reported at the end of daptomycin therapy; Nonevaluable - unable to determine response at the end of daptomycin therapy. Success was defined as cure or improved. Results: Fourteen patients are included in this analysis. Nine (64%) patients were female; 6 (43%) were ≥ 51 years of age. Two patients had an initial CrCl <30 mL/min, 1 was on hemodialysis. Eight (57%) patients had undergone allogeneic peripheral blood stem cell transplantation primarily for acute myeloid leukemia. The remaining 6 patients had papillary adenocarcinoma, endometrial carcinoma, dermatofibrosarcoma protuberans, acute lymphoblastic lymphoma, non-Hodgkin lymphoma, and Hodgkin lymphoma. The most common infection (n=11, 79%) was bacteremia; 7 (50%) patients had catheter-related bacteremia; 1 each (7%) had discitis, necrotizing fasciitis and urinary tract infection. Nine (64%) patients had vancomycin-resistant Enterococcus faecium (VRE) as a pathogen; 8 were bacteremic (3 with concurrent coagulase-negative staphylococci; CoNS). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated in 3 (21%) patients; 2 were bacteremic (1 with concurrent CoNS). One additional patient had CoNS bacteremia. The patient with necrotizing fasciitis was culture negative. The initial daptomycin dose was 4 mg/kg in 8 (57%) patients and 6 mg/kg in 6 (43%) patients. All patients receiving 6 mg/kg were bacteremic. The dosing frequency was adjusted for renal function in all patients. The median duration of therapy was 14.5 days (range, 2 – 62). Nine (64%) patients received an antibiotic prior to daptomycin and 43% of patients received an antibiotic concomitantly. Seven catheters were removed; 5 from patients with catheter-related bacteremia. The median time to clinical response was 2 days (n=10, range 1 – 13). All patients with an outcome reported (n=11) were successfully treated, 3 (21%) patients were nonevaluable. Of the 11 bacteremic patients, 5 received 4 mg/kg and 6 received 6 mg/kg; 2 were nonevaluable (both 6 mg/kg) and 9 of 11 (82%) were successes. Conclusion: These data demonstrate that daptomycin therapy is associated with clinical success in hem/onc patients including those who have undergone allogeneic peripheral blood stem cell transplantation where bacteremia and VRE are prevalent.