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 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
JournalThe Journal of antimicrobial chemotherapy
Volume68
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Daptomycin
Endocarditis
Safety
Therapeutics
Infection
Salvage Therapy
Enterococcus faecium
Enterococcus
Methicillin-Resistant Staphylococcus aureus
Creatine Kinase
Staphylococcus

Keywords

  • Infections
  • MRSA
  • Patient outcomes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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

A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis. / Kullar, Ravina; Casapao, Anthony M.; Davis, Susan L.; Levine, Donald P.; Zhao, Jing J.; Crank, Christopher W.; Segreti, John; Sakoulas, George; Cosgrove, Sara; Rybak, Michael J.

In: The Journal of antimicrobial chemotherapy, Vol. 68, No. 12, dkt294, 12.2013, p. 2921-2926.

Research output: Contribution to journalArticle

Kullar, R, Casapao, AM, Davis, SL, Levine, DP, Zhao, JJ, Crank, CW, Segreti, J, Sakoulas, G, Cosgrove, S & Rybak, MJ 2013, 'A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis', The Journal of antimicrobial chemotherapy, vol. 68, no. 12, dkt294, pp. 2921-2926. https://doi.org/10.1093/jac/dkt294
Kullar, Ravina ; Casapao, Anthony M. ; Davis, Susan L. ; Levine, Donald P. ; Zhao, Jing J. ; Crank, Christopher W. ; Segreti, John ; Sakoulas, George ; Cosgrove, Sara ; Rybak, Michael J. / A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis. In: The Journal of antimicrobial chemotherapy. 2013 ; Vol. 68, No. 12. pp. 2921-2926.
@article{b8df4570b60946a5bbb68ddc1b09657d,
title = "A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis",
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.",
keywords = "Infections, MRSA, Patient outcomes",
author = "Ravina Kullar and Casapao, {Anthony M.} and Davis, {Susan L.} and Levine, {Donald P.} and Zhao, {Jing J.} and Crank, {Christopher W.} and John Segreti and George Sakoulas and Sara Cosgrove and Rybak, {Michael J.}",
year = "2013",
month = "12",
doi = "10.1093/jac/dkt294",
language = "English (US)",
volume = "68",
pages = "2921--2926",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis

AU - Kullar, Ravina

AU - Casapao, Anthony M.

AU - Davis, Susan L.

AU - Levine, Donald P.

AU - Zhao, Jing J.

AU - Crank, Christopher W.

AU - Segreti, John

AU - Sakoulas, George

AU - Cosgrove, Sara

AU - Rybak, Michael J.

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

KW - Infections

KW - MRSA

KW - Patient outcomes

UR - http://www.scopus.com/inward/record.url?scp=84887538700&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887538700&partnerID=8YFLogxK

U2 - 10.1093/jac/dkt294

DO - 10.1093/jac/dkt294

M3 - Article

VL - 68

SP - 2921

EP - 2926

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 12

M1 - dkt294

ER -