Use of Daptomycin in the Treatment of Vancomycin-Resistant Enterococcal Urinary Tract Infections

A Short Case Series

Divya Pradeep Ramaswamy; Maria Amodio-Groton; Stephen J Scholand

Disclosures

BMC Urol. 2013;13(33) 

In This Article

Background

In the United States, the Gram-positive bacterium Enterococcus accounts for 12% of all cases of hospital-acquired infection and is most often implicated in urinary tract infections (UTIs).[1–3] Recent data show that approximately 33% of all clinical enterococcal isolates in the United States are vancomycin-resistant enterococci (VRE).[2] In North America, VRE are mainly derived from the species Enterococcus faecium (92.8%) and Enterococcus faecalis (6.7%).[4] In the past decade, VRE have become increasingly involved in nosocomial infections in the United States,[5,6] which has resulted in excessive morbidity, mortality, and health care costs.[7] Nearly 10% of all urinary enterococcal isolates in the United States are VRE; most of these are also E. faecium (88.4%).[3]

Because VRE, particularly E. faecium strains, exhibit resistance to many antimicrobials traditionally used to target vancomycin-susceptible isolates, the treatment of patients with VRE UTIs remains a challenge for the clinician.[8] Indeed, no drugs are approved by the US Food and Drug Administration (FDA) for the treatment of patients with VRE UTIs, and reliable clinical data about the optimal management of VRE UTIs are lacking in the scientific literature.[7] Among the therapeutic options to be considered are those that have demonstrated activity against VRE in vitro, including older agents such as doxycycline, fosfomycin, and nitrofurantoin and newer agents such as daptomycin, linezolid, quinupristin–dalfopristin, and tigecycline.[3,7,9]

Daptomycin is a bactericidal cyclic lipopeptide approved by the FDA for the management of complicated skin and skin structure infections caused by susceptible isolates of a variety of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, and for the management of bacteremia, including that associated with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates of S. aureus.[10] Although the approved use of daptomycin in enterococcal infections is limited to the treatment of patients with complicated skin and skin structure infections caused by vancomycin-susceptible isolates of E. faecalis,[10] 100% and 99.7% of vancomycin-resistant E. faecalis and E. faecium, respectively, were susceptible to daptomycin in more than 700 nonurinary VRE strains collected in the United States between 2007 and 2008.[11] The daptomycin minimal inhibitory concentration required for 90% inhibition (MIC90) of vancomycin-resistant E. faecalis was determined to be 1 μg/mL, whereas that for vancomycin-resistant E. faecium was 2 μg/mL.[11] The use of daptomycin is a particularly promising pharmacotherapeutic approach against VRE UTIs because 50% to 70% of the dose is excreted unchanged in the urine 24 hours after intravenous administration compared with 30% to 40% for linezolid, 15% to 19% for quinupristin–dalfopristin, and 20% to 30% for tigecycline.[7] Moreover, another case series has described the successful use of daptomycin in patients with VRE UTIs.[12]

In light of the scarcity of treatment options for VRE UTI and clinical data related to daptomycin use in this setting, the purpose of this report is to describe the clinical experience with daptomycin as part of the management of VRE UTIs in our acute care hospital. Our objective is to offer further evidence supporting daptomycin as a viable approach to managing a continuing therapeutic challenge.

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