Daptomycin exposure precedes infection and/or colonization with daptomycin non-susceptible enterococcus

Abstract

BackgroundDaptomycin non-susceptible enterococci (DNSE) are emerging as an important cause of healthcare-associated infection, however little is known about the epidemiology of DNSE. At the University of Iowa Hospitals and Clinics (UIHC) an increase in the frequency of patients infected and/or colonized with DNSE has occurred. The goals of this study were to evaluate potential factors associated with the development of DNSE colonization and/or infection and to compare the characteristics of patients with prior daptomycin exposure to those without prior daptomycin exposure.MethodsThe study is a retrospective case-series involving all patients with DNSE infection and/or colonization at UIHC, a 734-bed academic referral center, from June 1, 2005 to June 1, 2011.ResultsThe majority of patients with DNSE colonization and/or infection had prior daptomycin exposure (15 of 25; 60%), a concomitant gastrointestinal process (19 of 25; 76%), or were immunosuppressed (21 of 25; 84%). DNSE infection was confirmed in 17 of 25 (68%) patients, including 9 patients with bacteremia. Twelve of 17 (71%) patients with DNSE infection had prior daptomycin exposure, including 7 of 9 (78%) patients with bacteremia. Compared to patients without prior daptomycin exposure, patients with prior daptomycin exposure were less likely to harbor E. faecalis (0% vs. 33%; p = 0.019). A high proportion of patients (10 of 25; 40%) died during their hospitalizations. Most enterococcal isolates were E. faecium (86%), and were vancomycin-resistant (72%). Molecular typing revealed a diverse population of DNSE.ConclusionsPrior daptomycin exposure, immunosuppression, and/or a concomitant gastrointestinal process, may be associated with the development of DNSE. PFGE revealed a diverse population of DNSE, which along with both increasing numbers of DNSE detected yearly and increasing annual rates of daptomycin usage, suggests the emergence of DNSE under antimicrobial pressure.

Identification of a Novel Clone, ST736, among Enterococcus faecium Clinical Isolates and Its Association with Daptomycin Nonsusceptibility

“…Daptomycin-nonsusceptible enterococci, however, are emerging as a cause of health careassociated infection (4,6) and may be fairly common; they comprised 3.9% of 2,029 Enterococcus faecium isolates from U.S. hospitals over the period 2007 to 2010 (13) and 15.2% among VRE blood isolates at a New York cancer center (14). In addition to some earlier case reports (reviewed in reference 4), a notable increase in the number of patients infected or colonized with daptomycin-nonsusceptible enterococci has been reported from different geographic regions in the United States (14)(15)(16)(17)(18)(19).…”

“…Most patients develop resistance during daptomycin therapy (18,20,21). De novo resistance is also reported for some patients without prior use of daptomycin (16,22).…”

“…Based on whole-genome analysis of a very few clinical and laboratory-derived strains, mutations in several genes have been implicated in the development of daptomycin resistance in enterococci (15,(23)(24)(25)(26). The emergence and spread of daptomycinnonsusceptible enterococci in distinct patient populations or geographic regions are likely caused by a diverse population of enterococci (14,18). Such studies are largely restricted due to the lack of sufficient daptomycin-nonsusceptible clinical isolates.…”

Biochemical Characterization of Cardiolipin Synthase Mutations Associated with Daptomycin Resistance in Enterococci

“…While DAP susceptibility among enterococci remains Ͼ99%, continued use of DAP will likely increase the frequency of resistance worldwide (12). Several studies have already reported the development of resistance in both S. aureus (6,(13)(14)(15)(16) and enterococci (2,(17)(18)(19). Recent evidence strongly suggests that DAP inserts into the plasma membrane in a calcium-dependent manner and subsequently disrupts the functional integrity of the cell membrane, altering cell division.…”

“…nterococci are important pathogens responsible for serious infections, such as urinary tract infections, bacteremia, skin and soft tissue infections, endocarditis, and meningitis, and they are a major contributor to nosocomial infections in the United States (1,2). Enterococcus faecalis and E. faecium are responsible for the majority of clinical infections, and their treatment has become increasingly problematic as more than 80% of E. faecium isolates are now resistant to ampicillin and vancomycin (1).…”