The decision model indicated that use of voriconazole as the preferred antifungal agent in adult haematology patients with febrile neutropenia should result in lower overall treatment costs relative to LAmB.

18581 Background: Practice guidelines for empiric therapy of FN were created and implemented at our institution in January 2003, prior to which empiric therapy often included the use of cefp. These guidelines recommend the combination of pip/tazo with gentamicin or levofloxacin for most patients. This retrospective chart review compared the efficacy of pip/tazo combination therapy versus historical controls treated with cefp. Methods: 183 patients met eligibility criteria. 87 patients were treated with pip/tazo, with 92% receiving levofloxacin as the second agent. 75 patients received cefp, 16 of which initially also received either a fluoroquinolone or an aminoglycoside. Endpoints included a difference in the addition of vancomycin and antifungals, incidence of breakthrough infections, trends in antibiotic resistance, and survival until discharge. Groups were compared using chi-square or Student’s t-test as appropriate. Results: The two groups were not significantly different in any measured demographic or clinical characteristic. No statistical difference was found between groups for the addition of vancomycin (cefp 43%, pip/tazo 41%; p = 0.9898) or antifungals (cefp 45%, pip/tazo 51%; p = 0.1346). The incidence of breakthrough infections was comparable (cefp 25%, pip/tazo 26%; p = 0.7461), and microorganism eradication rates were not different between groups (cefp 48%, pip/tazo 54%; p = 0.41). However, of those who developed a breakthrough infection, survival was lower in the cefp group (37% vs. 63%; p = 0.0389). Additionally, the rate of overall survival to discharge was significantly lower in patients initially treated with cefp (83% vs. 94%; p = 0.0193). The antibiograms of the hematology floors were compared for the 2 years prior to and after implementation of our FN guidelines; no change in susceptibilities was observed. Conclusions: From these results, we conclude that pip/tazo combination therapy is a reasonable alternative to cefp for empiric treatment of FN. [Table: see text]

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.