Background: Vancomycin-resistant Enterococcus faecium (VREF) bacteremia has been reported to be increasing in frequency and is associated with significant morbidity and mortality rates in patients with acute leukemia with prolonged neutropenia and VREF colonization. We report our experience with the prophylactic use of varying doses of daptomycin and other antibiotics active against VREF in this patient population and the development of a cluster of daptomycin-resistant E. faecium bacteremia and colonization cases.
Methods: A retrospective chart review was conducted of patients with acute leukemia and prolonged neutropenia with positive microbiological data for VREF bacteremia and/or colonization from July 2009 to June 2010. We collected susceptibility data of the VREF, use and dosage of empiric anti-VREF antibacterial therapy, and the incidence of breakthrough VREF bacteremia among patients with colonization.
Results: Breakthrough VREF bacteremia occurred at the following rates in patients with prolonged neutropenia receiving prophylactic anti-VREF therapy: 14.6% (7/48 patients) receiving daptomycin 6 mg/kg per day, 8.3% (2/24 patients) receiving daptomycin 8 mg/kg per day, 0% (0/13 patients) receiving linezolid, 40% (4/10 patients) receiving tigecycline, and 0% (0/3 patients) receiving dalfopristin-quinupristin.
Conclusions: Breakthrough VREF bacteremia was observed despite the use of daptomycin 6 mg/kg per day in patients with neutropenia and colonized VREF. Increasing the dosage of daptomycin to 8 mg/kg per day seemed to reduce this occurrence but breakthroughs were seen in the setting of daptomycin-resistant E. faecium colonization. Linezolid seems to be a promising option to prevent or treat VREF bacteremia in these patients. We recommend close monitoring for VREF colonization including susceptibility data to appropriately select empiric or prophylactic antimicrobial therapy directed against VREF in those patients with prolonged neutropenia.