A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis

Ravina Kullar, Anthony M. Casapao, Susan L. Davis, Donald P. Levine, Jing J. Zhao, Christopher W. Crank, John Segreti, George Sakoulas, Sara E. Cosgrove, Michael J. Rybak

Research output: Contribution to journalArticle

Abstract

Objectives: Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidityand mortality. The objectivewas to assess the safetyand efficacyof high-dose daptomycin, defined as ≥8 mg/kg/day, in patients with confirmed or suspected staphylococcal and/or enterococcal IE. Methods: This was a multicentre, retrospective observational study (2005-11). Adult patients, not undergoing haemodialysis, with blood cultures positive for staphylococci or enterococci and a definitive or possible diagnosis of IE, who received daptomycin ≥8 mg/kg/day (based on total body weight) for ≥72 h were included. Results: Seventy patients met the inclusion criteria and comprised 33 (47.1%) with right-sided IE (RIE), 35 (50%) with left-sided IE (LIE) and 2 with both RIE and LIE. Several patients had concomitant sites of infection, with bone/joint infection being most prevalent (12.9%). Sixty-five patients received daptomycin as salvage therapy. Pathogens were isolated from 64 patients, with methicillin-resistant Staphylococcus aureus as the most common organism (84.4%), followed by vancomycin-resistant Enterococcus faecium (7.8%). The median (IQR) daptomycin dose was 9.8 mg/kg/day (8.2-10.0 mg/kg/day), and was similar in RIE and LIE patients (9.8 and 9.3 mg/kg/day, respectively). A total of 24 (34.3%) received combination therapy. For those patients with pathogens isolated (n=64), the organismwaseradicated in 57 (89.1%) patients.Among64 clinically evaluable patients, 55 (85.9%) achieved clinical success. No patients required discontinuation of high-dose daptomycin due to creatine phosphokinase elevations. Conclusions: Patients with both RIE and LIE had successful outcomes with high-dose daptomycin therapy. Additional clinical trials evaluating high daptomycin dosages in patients with IE are warranted.

Original languageEnglish (US)
Article numberdkt294
Pages (from-to)2921-2926
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • Infections
  • MRSA
  • Patient outcomes

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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    Kullar, R., Casapao, A. M., Davis, S. L., Levine, D. P., Zhao, J. J., Crank, C. W., Segreti, J., Sakoulas, G., Cosgrove, S. E., & Rybak, M. J. (2013). A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis. Journal of Antimicrobial Chemotherapy, 68(12), 2921-2926. [dkt294]. https://doi.org/10.1093/jac/dkt294