A Pooled, Post-hoc Evaluation of the Length of Antibiotic Therapy from IGNITE1: A Phase 3 Study of Eravacycline (ERV) and Ertapenem (ETP) for Complicated Intra-Abdominal Infections (cIAI)

Author(s):
Holly Hoffman-Roberts, Tetraphase Pharmaceuticals; Patrick Scoble, Tetraphase Pharmaceuticals; Andrew Marsh, Tetraphase Pharmaceuticals; Philip Barie, Weill Medical College of Cornell University; Patrick Horn, Tetraphase Pharmaceuticals

Background:

A previous study has shown that in patients with cIAI after adequate source control procedures, outcomes were similar after short-courses of antibiotic therapy (~ 4 d) compared to longer courses of therapy (~ 8 d).

Hypothesis:

Patients with longer courses of antibiotic therapy for cIAI are a more complex patient population presenting with more comorbidities for whom clinicians choose to give longer antibiotic therapy.

Methods:

This was a post-hoc analysis from IGNITE1, a randomized, double-blind, non-inferiority phase 3 trial, made to describe patient demographics and outcomes by duration of therapy (DoRx). Patients with documented cIAI were randomized (1:1) to either ERV 1 mg/kg IV q12h or ETP 1g IV QD. DoRx was up to 14 d at the clinician’s discretion. Clinical outcome at the test of cure (TOC) visit, ~ 28 d after randomization, was the primary efficacy endpoint in the microbiological-intent-to-treat (micro-ITT) population. Data were pooled and three groups were stratified based on DoRx, < 5 d, 6 to 8 d, and > 8 d, respectively. Statistical analysis was performed using multi-group X² to compare data among groups, p < 0.05.

Results:

Patients who received longer DoRx had higher APACHE II scores, were older, had higher rates of bacteremia, were less likely to have a diagnosis of complicated appendicitis, and were more likely to have an open procedure as compared to those receiving shorter DoRx (Table). Overall average DoRx was 7 d, and for each of the groups were 4.2 d, 6.8 d, and 11.2 d, respectively. There was adequate source control in 98.2% of the patients. Clinical success rates for the stratified groups were 79.5%, 92.4%, and 83.7%, respectively (p< 0.01).

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Conclusions:

In IGNITE1, patients who received longer DoRx for cIAI were older, sicker, less likely to have appendicitis, more likely to be bacteremic, and more likely to undergo open surgery. DoRx was longer than in a recently published prospective study of short-course DoRx for cIAI except in the shortest DoRx group. Whether prolonged DoRx is indicated for more complex subpopulations deserves prospective evaluation.