A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis.
OBJECTIVE
Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidity and mortality. The objective was to assess the safety and efficacy of 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 organism was eradicated in 57 (89.1%) patients. Among 64 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.
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
Ravina
R
Kullar
Anthony M
AM
Casapao
Susan L
SL
Davis
Donald P
DP
Levine
Jing J
JJ
Zhao
Christopher W
CW
Crank
John
J
Segreti
George
G
Sakoulas
Sara E
SE
Cosgrove
Michael J
MJ
Rybak
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001769:Blood / Q000382:microbiology; D017576:Daptomycin / Q000008:administration & dosage* / Q000009:adverse effects*; D004696:Endocarditis / Q000188:drug therapy* / Q000382:microbiology; D016983:Enterococcus / Q000302:isolation & purification; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013211:Staphylococcus aureus / Q000302:isolation & purification; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D017576:Daptomycin
MRSA; infections; patient outcomes