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

Discussion

The data in this case series show daptomycin to be a safe and effective therapeutic option in the treatment of patients with VRE UTIs. Limitations of the present study include the fact that this is a retrospective case series with a small number of patients and clinical records that are often limited and variable. Furthermore, because of the paucity of data in the literature, it is unclear what the most appropriate daptomycin dose is for the treatment of VRE UTIs. Nevertheless, it is clear that VRE are increasingly involved in nosocomial infections. Of concern, VRE may transfer vancomycin resistance to other bacterial species, including S. aureus.[13] Uncontrolled dissemination of VRE infections within health care institutions has been facilitated by incautious contact with contaminated medical equipment and surfaces, colonized health care personnel, and infected patients.[14] For example, the spread of a strain of linezolid-resistant VRE has been reported in one zone of a transplantation unit despite extensive precautions.[15]

Another major factor that has led to the spread of VRE infection is poor infection control techniques that rely on cephalosporins and other antibacterials inactive against enterococci.[8] A recent report[7] found that more than 30% of all clinical isolates of Enterococcus were resistant to vancomycin, including more than 90% of E. faecium isolates. For these reasons, appropriate antibiotic susceptibility testing is a mainstay of good clinical practice to limit the spread of multidrug-resistant strains, and agents that have specific activity against these strains must be used to eradicate these difficult-to-treat infections.

The urinary tract is one of the main portals for entry of VRE, so it is hardly surprising that the urinary tract is a major site of infection.[13] Management of VRE UTIs usually requires correction of any factors contributing to the infection. Catheter removal, obstruction relief, abscess drainage, and initiation of antimicrobial therapy are all initial steps taken in clinical practice.[7]

In this case series, patients with VRE UTIs were treated with daptomycin, a cyclic lipopeptide antibiotic that has rapid bactericidal activity against a variety of Gram-positive pathogens.[16] Daptomycin acts by binding to bacterial cell membranes and inducing rapid depolarization, which inhibits DNA, RNA, and protein synthesis and leads to cell death.[10] In the 10 cases described here, daptomycin was chosen as the treatment option because of its efficacy profile, sensitivity testing, and low resistance rates for both major species of Enterococcus.

Another important consideration when appropriate treatment for VRE UTI is chosen is the presence of intact drug at the site of infection.[16] Daptomycin is eliminated primarily by the kidney; approximately 52% is excreted unchanged into the urine after intravenous administration.[10] Other agents active against VRE, such as linezolid, quinupristin–dalfopristin, and tigecycline, have a lower fraction of urinary excretion,[7] which may potentially limit their effectiveness in the management of VRE UTIs.

Most strains of VRE are resistant to penicillin and ampicillin, although higher-dose ampicillin, doxycycline, and nitrofurantoin remain viable treatment options. More often, drug choices used to treat VRE include daptomycin, linezolid, quinupristin–dalfopristin, and tigecycline. These compounds have similarly low MIC values against VRE species.[7] All these antibiotics except daptomycin exhibit bacteriostatic properties; daptomycin is bactericidal.[7] Daptomycin has similar MIC values for E. faecium and E. faecalis[7] and is effective in treating either pathogen. Daptomycin resistance among VRE strains remains rare;[11] numerous global surveillance studies have demonstrated higher susceptibility levels in VRE strains using daptomycin than in strains using linezolid or quinupristin–dalfopristin.[16] Resistance to linezolid among VRE isolates has been well described and is of increasing clinical concern.[16–19] Quinupristin–dalfopristin has limited activity against E. faecalis.[7] In addition, vancomycin-resistant E. faecium strains have shown emerging resistance to quinupristin–dalfopristin; 3.4% of urinary tract isolates were resistant in a study at 28 medical centers in the United States.[3] Use of quinupristin–dalfopristin is also limited by its potential systemic and infusion site–related adverse effects, including myalgia and arthralgia.[7,13]

Our experience confirms and extends the findings of a previous case series on the use of daptomycin for the treatment of VRE UTIs. The previous study[12] of 5 hospitalized patients with indwelling catheters and VRE UTIs who received 5-day courses of daptomycin showed that all patients achieved complete eradication of infection at daptomycin doses of 1.4 to 3.7 mg/kg daily. Taken together, these case studies emphasize the importance of further analyses to delineate the appropriate doses of daptomycin for the treatment of patients with VRE UTIs.

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