Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI)

April 30, 2015 at 2:16 pm

Clin Infec Dis May 15, 2015 V.60 N.10 P.1462-1471

Joseph Solomkin, Ellie Hershberger, Benjamin Miller, Myra Popejoy, Ian Friedland, Judith Steenbergen, Minjung Yoon, Sylva Collins, Guojun Yuan, Philip S. Barie, and Christian Eckmann

1Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio

2Cubist Pharmaceuticals, Lexington, Massachusetts

3Departments of Surgery and Medicine, Weill Cornell Medical College, New York, New York

4Department of General, Visceral and Thoracic Surgery, Academic Hospital of Medical University Hannover, Peine, Germany

Correspondence: Joseph Solomkin, MD, Department of Surgery, University of Cincinnati College of Medicine, 6005 Given Rd, Cincinnati, Ohio 45243 (solomkjs{at}ucmail.uc.edu) . 

Background

Increasing antimicrobial resistance among pathogens causing complicated intra-abdominal infections (cIAIs) supports the development of new antimicrobials. Ceftolozane/tazobactam, a novel antimicrobial therapy, is active against multidrug-resistant Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae.

Methods

ASPECT-cIAI (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam in Complicated Intra-abdominal Infections) was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) every 8 hours or meropenem (1 g) every 8 hours intravenously for 4–14 days. The prospectively defined objectives were to demonstrate statistical noninferiority in clinical cure rates at the test-of-cure visit (24–32 days from start of therapy) in the microbiological intent-to-treat (primary) and microbiologically evaluable (secondary) populations using a noninferiority margin of 10%. Microbiological outcomes and safety were also evaluated.

Results

Ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in the primary (83.0% [323/389] vs 87.3% [364/417]; weighted difference, −4.2%; 95% confidence interval [CI], −8.91 to .54) and secondary (94.2% [259/275] vs 94.7% [304/321]; weighted difference, −1.0%; 95% CI, −4.52 to 2.59) endpoints, meeting the prespecified noninferiority margin. In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 95.8% (23/24) and 88.5% (23/26) in the ceftolozane/tazobactam plus metronidazole and meropenem groups, respectively, and 100% (13/13) and 72.7% (8/11) in patients with CTX-M-14/15 ESBLs. The frequency of adverse events (AEs) was similar in both treatment groups (44.0% vs 42.7%); the most common AEs in either group were nausea and diarrhea.

Conclusions

Treatment with ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in adult patients with cIAI, including infections caused by multidrug-resistant pathogens.

Clinical Trials Registration.NCT01445665 and NCT01445678.

PDF

http://cid.oxfordjournals.org/content/60/10/1462.full.pdf+html

Entry filed under: Antimicrobianos, Bacterias, Bacteriemias, Epidemiología, Infecciones intraabdominales, Metodos diagnosticos, Resistencia bacteriana, Sepsis. Tags: .

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