- Crank, Christopher W.
- Davis, Susan L.
- Rybak, Michael J.
- Levine, Donald P.
- Kullar, Ravina
- Cosgrove, Sara E.
- Potoski, Brian A.
- Casapao, Anthony M.
- Zhao, Jing J.
- Segreti, John
- Sakoulas, George
- Goff, Debra A.
|Abstract or Summary
- Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-
resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at>6 mg/kg of body weight/day may be used
to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin)
therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics
and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by
Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections
included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and
duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively.
The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients.
The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate
was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients
(3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated
CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication
in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections.
No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the
treatment of enterococcal infections.
- Casapao, A. M., Sakoulas, G., Cosgrove, S. E., Rybak, M. J., Kullar, R., Davis, S. L., . . . Segreti, J. (2013). Multicenter study of high-dose daptomycin for treatment of enterococcal infections. Antimicrobial Agents and Chemotherapy, 57(9), 4190-4196. doi:10.1128/AAC.00526-13
|Funding Statement (additional comments about funding)
- A.M.C. has received
grant support from Cubist Pharmaceuticals, Forest Laboratories, and the
Michigan Department of Community Health. S.L.D. has served on the
advisory board of Forest Laboratories. M.J.R. received speaking or consulting
honoraria or grant support from Cubist, Forest, and Clinical Therapeutics
and is funded in part by NIAID. D.P.L. has served as a consultant
for, received grant support from, or served on speakers’ bureaus for Cubist,
Astellas, Forest, Theravance, and Rib-X. B.A.P. has received grant
support from Cubist. D.A.G. has received grant support from and has
served as a consultant or on the speakers’ bureaus for Merck, Cepheid,
Forest, Optimer, Cubist, and AdvanDx. J.S. has received grant support
from and served on the speakers’ bureau for Cubist. G.S. has received
grant support from or served on speakers’ bureaus for Cubist, Forest, and
Pfizer. S.E.C. has received grant support from or served as a consultant for
Cubist, Astellas, and AdvanDx. C.W.C. and J.J.Z. have no conflicts of