1. A post-hoc evaluation of the length of antibiotic therapy from IGNITE4: A phase 3 study of eravacycline and meropenem for complicated intra-abdominal infections
Kenneth Lawrence1, Erin Mathias2, Melanie Olesky1, Ekaterina Efimova1 , Larry Tsai1 ,Philip S. Barie3
1Tetraphase Pharmaceuticals, Watertown, MA
2Veristat, Southborough, MA
3Weill Cornell Medicine, New York, NY
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2. Disclosures KL, MO, EE are employees of Tetraphase Pharmaceuticals
EM is an employee of Veristat
PSB no financial relationships
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3. Background
Eravacycline is a novel, fully-synthetic fluorocycline antibiotic that has completed phase 3 clinical development for patients with cIAI.
In IGNITE1 and IGNITE4, IV eravacycline met the primary endpoint of non- inferiority of clinical response compared to ertapenem and meropenem, respectively, and was generally well tolerated.
This analysis was performed to assess prescribing of antibiotic therapy for cIAI subsequent to STOP-IT with respect to duration, and to determine patient- or disease-related characteristics related to shorter treatment courses, regardless of patient severity of illness.
Sawyer et al. N Engl J Med 2015;372:
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4. Methods
IGNITE4 was a double-blind, inferiority phase 3 trial in which patients with documented cIAI were randomized (1:1) to receive either eravacycline or meropenem for 4-14 days (d).
Three groups were categorized based on duration of treatment: < 5 d, 5.5 to 8 d, and > 8 d.
Statistical analysis assessed the association of several collected patient variables using multi-group Χ2 to compare data among groups (p < 0.05).
Ordinal logistic regression was performed with all variables having a univariate association with duration of therapy.
Tsai L, et al. 28th ECCMID Madrid, Spain. O0421
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5. Results
Patients who received longer duration of therapy had the following:
APACHE II score ≥ 10
Less likely to have a diagnosis of complicated appendicitis
More likely to have an open surgical procedure
APACHE II score ≥ 10 was not significant after adjusting for diagnosis and open surgical procedure.
Average duration of therapy for all patients was 7.4 d, and for the groups were 4.6 d, 7.2 d, and 12.3 d, respectively.
Clinical successes in the micro-ITT group for the three groups were 88.4%, 94.5%, and 87.0%, respectively.
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6. Complicated Appendicitis
Results
Characteristic
Group
≤5 days
(n=121)
5.5 to 8 days (n=201)
>8 days
(n=77)
p-value [1]
Age (years)
< 65
65-75
≥ 75
96 (79.3%)
16 (13.2%)
9 ( 7.4%)
145 (72.1%)
35 (17.4%)
21 (10.4%)
51 (66.2%)
16 (20.8%)
10 (13.0%)
0.358
APACHE II ≥ 10
40 (19.9%)
23 (29.9%)
0.016
Presence of Bacteremia
7 ( 5.8%)
19 ( 9.5%)
5 ( 6.5%)
0.442
Diagnosis
Complicated Appendicitis
76 (62.8%)
87 (43.3%)
20 (26.0%)
<0.001
Open Procedure
59 (48.8%)
126 (62.7%)
62 (80.5%)
BMI ≥ 30
32 (26.4%)
62 (30.8%)
26 (33.8%)
0.519
Presence of Diabetes
9 (11.7%)
0.599
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[1] p-value from chi-square test for univariate associations

7. Results APACHE II ≥ 10 1.48 0.91 – 2.41 Open Procedure 2.47
Characteristic
Odds Ratio [1]
95% CI [1]
APACHE II ≥ 10
1.48
0.91 – 2.41
Open Procedure
2.47
1.66 – 3.69
Other cIAI diagnosis
2.67
1.79 – 3.99
[1] Odds ratio and 95% confidence interval (CI) from an ordinal logistic regression model containing all characteristics
having a significant univariate association with DoRx
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8. Conclusions
In IGNITE4, patients receiving longer courses of antibiotic treatment were sicker, had a non appendiceal diagnosis, and were more likely to have an open surgical procedure.
Compared to IGNITE1, fewer patient- and disease-related characteristics were associated with longer duration of treatment in IGNITE4.
Non appendiceal diagnosis and open surgical procedure were significantly associated with longer treatment duration in both IGNITE1 and IGNITE4.
Average duration of treatment exceeded that in the short-course treatment group in STOP-IT and were similar to those in IGNITE1.
Hoffman-Roberts HL, et al. 36th SIS Annual Meeting 2016
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