Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia.
OBJECTIVE
We sought to compare daptomycin with ceftriaxone for the treatment of patients with community-acquired pneumonia (CAP).


METHODS
Two phase-3 randomized, double-blind trials that enrolled adult patients hospitalized with CAP were conducted. Patients received intravenous daptomycin (4 mg/kg) or ceftriaxone (2 g) once daily for 5-14 days. Aztreonam could be added for patients with gram-negative infections. Clinical responses at the test-of-cure visit among patients in the intent-to-treat and clinically evaluable populations were the primary efficacy end points.


RESULTS
After combining data from the trials, the intent-to-treat population included 413 daptomycin-treated patients and 421 ceftriaxone-treated patients, and the clinically evaluable population included 369 daptomycin-treated patients and 371 ceftriaxone-treated patients. In the intent-to-treat population, the clinical cure rate among daptomycin-treated patients with CAP was 70.9%, compared with 77.4% among ceftriaxone-treated patients (95% confidence interval for the difference between cure rates, -12.4% to -0.6%). In the clinically evaluable population, the clinical cure rate was lower among daptomycin-treated patients (79.4%) than among ceftriaxone-treated patients (87.9%; 95% confidence interval for the difference between cure rates, -13.8% to -3.2%). A posthoc analysis revealed that, among those who had received up to 24 h of prior effective therapy, cure rates were similar among daptomycin-treated (90.7%) and ceftriaxone-treated patients (88.0%; 95% confidence interval for the difference between cure rates, -6.1% to 11.5%).


CONCLUSIONS
Daptomycin is not effective for the treatment of CAP, including infections caused by Streptococcus pneumoniae and Staphylococcus aureus. The observation that as little as 24 h of prior effective therapy may impact clinical outcome suggests that trials to evaluate CAP treatment may need to exclude patients who have received any potentially effective therapy before enrollment.
Pertel
Peter E
PE
Cubist Pharmaceuticals, Lexington, Massachusetts 02421, USA. peter.pertel@cubist.com
Bernardo
Patricia
P
Fogarty
Charles
C
Matthews
Peter
P
Northland
Rebeca
R
Benvenuto
Mark
M
Thorne
Grace M
GM
Luperchio
Steven A
SA
Arbeit
Robert D
RD
Alder
Jeff
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D002443:Ceftriaxone / Q000009:adverse effects / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D017576:Daptomycin / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011014:Pneumonia / Q000188:drug therapy* / Q000473:pathology; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000473:pathology; D018805:Sepsis / Q000188:drug therapy / Q000473:pathology; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D017576:Daptomycin