Randomized, multicenter, double-blind study of efficacy, safety, and tolerability of intravenous ertapenem versus piperacillin/tazobactam in treatment of complicated intra-abdominal infections in hospitalized adults.
BACKGROUND
Complicated intra-abdominal infections are a common problem in surgical practice. This study compared the effectiveness of ertapenem (1 g qd) and piperacillin/tazobactam (3.375 g q6h) in the treatment of these infections.


METHODS
This was a multicenter, double-blinded, randomized study conducted in patients with complicated intra-abdominal infections. Of the 535 patients screened, 500 were stratified on the basis of disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score < or =10 or >10), then randomized (1:1) to 4-14 days of treatment with one of the regimens and six weeks of followup. Nearly all patients (N = 494) were treated. The primary endpoint was the proportion of microbiologically evaluable patients with a favorable clinical response (cure) at two weeks. Non-inferiority of ertapenem was based on a difference in response rate of <15 percentage points compared with piperacillin/tazobactam (lower bound of the 95% CI > -15).


RESULTS
Of the 494 treated patients, 231 were microbiologically evaluable, with 123 and 108 patients in the ertapenem and piperacillin/tazobactam groups, respectively. Statistically similar cure rates were observed in the ertapenem (82.1%) and piperacillin/tazobactam (81.7%) groups (difference 0.3 [95% CI: -9.6, 10.5]). The pathogens isolated most frequently were Escherichia coli, Bacteroides fragilis, and Bacteroides thetaiotamicron, typical isolates associated with intra-abdominal infections. There were no statistical differences between the groups in serious drug-related clinical adverse events, drug-related clinical adverse experiences leading to study discontinuation, or mortality.


CONCLUSIONS
Ertapenem was non-inferior to piperacillin/tazobactam in the cure of intra-abdominal infections caused by susceptible pathogens. Both study drugs generally were well tolerated.
Namias
Nicholas
N
Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33101, USA. nnamias@miami.edu
Solomkin
Joseph S
JS
Jensen
Erin H
EH
Tomassini
Joanne E
JE
Abramson
Murray A
MA
D018806:APACHE; D018784:Abdominal Abscess / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D001439:Bacteroides / Q000302:isolation & purification; D004311:Double-Blind Method; D000077727:Ertapenem; D004926:Escherichia coli / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D010538:Peritonitis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D010878:Piperacillin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D047090:beta-Lactams / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000077727:Ertapenem; D010878:Piperacillin